PedAM

Pediatric Disease Annotations & Medicines


	amyotrophic lateral sclerosis 1

Disease ID	1862
Disease	amyotrophic lateral sclerosis 1
Synonym	amyotrophic lateral sclerosis 1, autosomal dominant amyotrophic lateral sclerosis 1, familial amyotrophic lateral sclerosis, autosomal dominant amyotrophic lateral sclerosis, familial fals
OMIM	OMIM:105400
DOID	DOID:0060193
UMLS	C1862939
Curated Gene	Entrez_id \| Symbol \| Resource(Total Genes:49) TNF \| 7124 \| CTD_human SOD1 \| 6647 \| CLINVAR;CTD_human;UNIPROT PON1 \| 5444 \| CTD_human CNTF \| 1270 \| CTD_human CD68 \| 968 \| CTD_human CTSD \| 1509 \| CTD_human RXRA \| 6256 \| CTD_human CALB2 \| 794 \| CTD_human BCL2L1 \| 598 \| CTD_human CREBBP \| 1387 \| CTD_human DCTN1 \| 1639 \| CTD_human;UNIPROT JAK3 \| 3718 \| CTD_human CST3 \| 1471 \| CTD_human TLE3 \| 7090 \| CTD_human GABRA1 \| 2554 \| CTD_human FOS \| 2353 \| CTD_human VIM \| 7431 \| CTD_human LDLR \| 3949 \| CTD_human SELPLG \| 6404 \| CTD_human CLU \| 1191 \| CTD_human GRIA3 \| 2892 \| CTD_human CASP1 \| 834 \| CTD_human GBX2 \| 2637 \| CTD_human PENK \| 5179 \| CTD_human NEFH \| 4744 \| CTD_human OTOG \| 340990 \| CTD_human PDGFA \| 5154 \| CTD_human JUND \| 3727 \| CTD_human LAT \| 27040 \| CTD_human GFAP \| 2670 \| CTD_human ANG \| 283 \| CTD_human PRPH \| 5630 \| CTD_human GSX2 \| 170825 \| CTD_human HSF1 \| 3297 \| CTD_human GDI1 \| 2664 \| CTD_human TIAM1 \| 7074 \| CTD_human XIAP \| 331 \| CTD_human TMSB4X \| 7114 \| CTD_human SIX2 \| 10736 \| CTD_human WNT7A \| 7476 \| CTD_human DBX1 \| 120237 \| CTD_human FGF6 \| 2251 \| CTD_human KIF3C \| 3797 \| CTD_human SNAI1 \| 6615 \| CTD_human BSG \| 682 \| CTD_human CD7 \| 924 \| CTD_human FMO1 \| 2326 \| CTD_human SHC1 \| 6464 \| CTD_human INA \| 9118 \| CTD_human
Inferring Gene	(Waiting for update.)
Text Mined Gene	(Waiting for update.)
Locus	(Waiting for update.)

Disease ID	1862
Disease	amyotrophic lateral sclerosis 1
Integrated Phenotype	HPO \| Name(Total Integrated Phenotypes:11) HP:0001324 \| Muscular weakness HP:0010535 \| Sleep apnea HP:0007024 \| Pseudobulbar palsy HP:0007354 \| Amyotrophic lateral sclerosis HP:0003202 \| Neurogenic muscle atrophy, especially in the lower limbs HP:0002314 \| Degeneration of the lateral corticospinal tracts HP:0002380 \| Muscle twitch HP:0003394 \| Muscle cramps HP:0002398 \| Anterior horn cell loss HP:0001257 \| Spasticity HP:0001347 \| Hyperreflexia
Text Mined Phenotype	(Waiting for update.)

Disease ID	1862
Disease	amyotrophic lateral sclerosis 1
Manually Symptom	(Waiting for update.)
Text Mined Symptom	(Waiting for update.)

Manually Genotype(Total Text Mining Genotypes:0)
(Waiting for update.)

All Snps(Total Genotypes:124)
snpId	pubmedId	geneId	geneSymbol	diseaseId	sourceId	sentence	score	Year	geneSymbol_dbSNP	CHROMOSOME	POS	REF	ALT
rs11556620	8592323	6647	SOD1	umls:C1862939	UNIPROT	Familial amyotrophic lateral sclerosis/motor neurone disease (FALS): a review of current developments.	0.52	1995	SOD1	21	31667278	A	G
rs121909329	23349634	7415	VCP	umls:C1862939	BeFree	This stimulatory effect was lost when we used VCP mutants (R155H, R159G, and R191Q) known to cause Inclusion Body Myopathy with Paget's disease of bone and Fronto-temporal Dementia (IBMPFD) and/or familial Amyotrophic Lateral Sclerosis (ALS).	0.003528744	2013	VCP	9	35065363	C	T,G
rs121909334	23349634	7415	VCP	umls:C1862939	BeFree	This stimulatory effect was lost when we used VCP mutants (R155H, R159G, and R191Q) known to cause Inclusion Body Myopathy with Paget's disease of bone and Fronto-temporal Dementia (IBMPFD) and/or familial Amyotrophic Lateral Sclerosis (ALS).	0.003528744	2013	VCP	9	35065255	C	T
rs121909668	24509083	2521	FUS	umls:C1862939	BeFree	Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1).	0.012214884	2013	FUS	16	31191418	C	G,T
rs121909668	22878663	2521	FUS	umls:C1862939	BeFree	FUS/TLS-immunoreactive neuronal and glial cell inclusions increase with disease duration in familial amyotrophic lateral sclerosis with an R521C FUS/TLS mutation.	0.012214884	2012	FUS	16	31191418	C	G,T
rs121909668	24509083	3065	HDAC1	umls:C1862939	BeFree	Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1).	0.000271442	2013	FUS	16	31191418	C	G,T
rs121912431	17316906	6647	SOD1	umls:C1862939	BeFree	These models express G37R mutant Cu/Zn superoxide dismutase (SOD1G37R; fALS), A53T mutant alpha-synuclein (alpha-SynA53T; PD), full-length mutant atrophin-1-65Q, and htt-N171-82Q (huntingtin N-terminal fragment; HD).	0.52	2008	SOD1	21	31663829	G	A
rs121912431	12060716	3315	HSPB1	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.000271442	2002	SOD1	21	31663829	G	A
rs121912431	20485746	6647	SOD1	umls:C1862939	BeFree	The G37R, one of the many SOD1 mutations known to be associated to FALS, is difficult to be reconciled with this model because it is located far from the metal sites and the monomer-monomer interface.	0.52	2010	SOD1	21	31663829	G	A
rs121912431	17683122	6647	SOD1	umls:C1862939	BeFree	The G37R copper-zinc superoxide dismutase (SOD1) is one of the many mutant SOD1 proteins known to cause familial amyotrophic lateral sclerosis by an unknown mechanism.	0.52	2007	SOD1	21	31663829	G	A
rs121912431	12710516	6647	SOD1	umls:C1862939	BeFree	Familial amyotrophic lateral sclerosis with a point mutation (G37R) of the superoxide dismutase 1 gene: a clinicopathological study.	0.52	2002	SOD1	21	31663829	G	A
rs121912431	11181815	6647	SOD1	umls:C1862939	BeFree	Transfection of these cell lines with DNA encoding two mutant SOD1 enzymes (G37R and G85R) associated with familial amyotrophic lateral sclerosis (FALS), produced similar, but more severe changes, i.e.	0.52	2001	SOD1	21	31663829	G	A
rs121912431	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31663829	G	A
rs121912431	12060716	6647	SOD1	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.52	2002	SOD1	21	31663829	G	A
rs121912431	12060716	3308	HSPA4	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.000814326	2002	SOD1	21	31663829	G	A
rs121912431	9052802	6647	SOD1	umls:C1862939	BeFree	High levels of familial Amyotrophic Lateral Sclerosis (ALS)-linked SOD1 mutants G93A and G37R were previously shown to mediate disease in mice through an acquired toxic property.	0.52	1997	SOD1	21	31663829	G	A
rs121912432	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31663832	C	G
rs121912433	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31663841	G	A
rs121912433	21877919	6647	SOD1	umls:C1862939	BeFree	Recurrent G41S mutation in Cu/Zn superoxide dismutase gene (SOD1) causing familial amyotrophic lateral sclerosis in a large Polish family.	0.52	2012	SOD1	21	31663841	G	A
rs121912434	12060716	6647	SOD1	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.52	2002	SOD1	21	31663842	G	A
rs121912434	12060716	3315	HSPB1	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.000271442	2002	SOD1	21	31663842	G	A
rs121912434	12060716	3308	HSPA4	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.000814326	2002	SOD1	21	31663842	G	A
rs121912434	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31663842	G	A
rs121912435	24369116	6647	SOD1	umls:C1862939	BeFree	In this study, we have carried out a 20 ns molecular dynamics simulation for wild type (WT), H43R and W32F mutated SOD1's dimer and compared their structure and conformational properties by extracting several quantitative properties from the trajectory to understand the pathology of fALS disease.	0.52	2013	SOD1	21	31663848	A	G
rs121912435	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31663848	A	G
rs121912436	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667274	G	C
rs121912436	15738401	6647	SOD1	umls:C1862939	BeFree	In the presence of several of these molecules, A4V and other FALS-linked SOD1 mutants such as G93A and G85R behaved similarly to wild-type SOD1, suggesting that these compounds could be leads toward effective therapeutics against FALS.	0.52	2005	SOD1	21	31667274	G	C
rs121912436	18378676	6647	SOD1	umls:C1862939	BeFree	Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis.	0.52	2008	SOD1	21	31667274	G	C
rs121912436	11045671	6647	SOD1	umls:C1862939	BeFree	Advanced glycation endproduct-modified superoxide dismutase-1 (SOD1)-positive inclusions are common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutations and transgenic mice expressing human SOD1 with a G85R mutation.	0.52	2000	SOD1	21	31667274	G	C
rs121912436	11181815	6647	SOD1	umls:C1862939	BeFree	Transfection of these cell lines with DNA encoding two mutant SOD1 enzymes (G37R and G85R) associated with familial amyotrophic lateral sclerosis (FALS), produced similar, but more severe changes, i.e.	0.52	2001	SOD1	21	31667274	G	C
rs121912436	15050437	6647	SOD1	umls:C1862939	BeFree	Disruption of the structure of the Golgi apparatus and the function of the secretory pathway by mutants G93A and G85R of Cu, Zn superoxide dismutase (SOD1) of familial amyotrophic lateral sclerosis.	0.52	2004	SOD1	21	31667274	G	C
rs121912437	12531528	6647	SOD1	umls:C1862939	BeFree	In this study we have investigated the effects of over-expressing wild-type SOD1 and two mutant forms of SOD1 found in FALS, G93A and G93R, on cell survival using stably transfected neuronal cells.	0.52	2002	SOD1	21	31667298	G	C,T
rs121912437	19805550	6647	SOD1	umls:C1862939	BeFree	The structure and unfolding of metal-free (apo) human wild-type SOD1 and three pathogenic variants of SOD1 (A4V, G93R, and H48Q) that cause familial amyotrophic lateral sclerosis have been studied with amide hydrogen/deuterium exchange and mass spectrometry.	0.52	2009	SOD1	21	31667298	G	C,T
rs121912437	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667298	G	C,T
rs121912438	9382875	6647	SOD1	umls:C1862939	BeFree	Based on the temporal correlation of these impairments with the onset of motor weakness and the appearance of NF inclusions and vacuoles in vulnerable motor neurons, the latter lesions may be the proximal cause of motor neuron dysfunction and degeneration in the G93A mice and in FALS patients with SOD1 mutations.	0.52	1997	SOD1	21	31667299	G	C
rs121912438	11701756	6647	SOD1	umls:C1862939	BeFree	In a recent work, we have observed that calcineurin activity is depressed in two models for familial amyotrophic lateral sclerosis (FALS) associated with mutations of the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1), namely in neuroblastoma cells expressing either SOD1 mutant G93A or mutant H46R and in brain areas from G93A transgenic mice.	0.52	2001	SOD1	21	31667299	G	C
rs121912438	12060716	6647	SOD1	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.52	2002	SOD1	21	31667299	G	C
rs121912438	15050437	6647	SOD1	umls:C1862939	BeFree	Disruption of the structure of the Golgi apparatus and the function of the secretory pathway by mutants G93A and G85R of Cu, Zn superoxide dismutase (SOD1) of familial amyotrophic lateral sclerosis.	0.52	2004	SOD1	21	31667299	G	C
rs121912438	12384220	6647	SOD1	umls:C1862939	BeFree	Degeneration of corticospinal and bulbospinal systems in the superoxide dismutase 1(G93A G1H) transgenic mouse model of familial amyotrophic lateral sclerosis.	0.52	2002	SOD1	21	31667299	G	C
rs121912438	12060716	3308	HSPA4	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.000814326	2002	SOD1	21	31667299	G	C
rs121912438	8610185	6647	SOD1	umls:C1862939	BeFree	Transgenic mice (line G1H) expressing a human SOD1 containing a mutation of Gly-93 --> Ala (G93A) develop a motor neuron disease similar to familial amyotrophic lateral sclerosis, but transgenic mice (line N1029) expressing a wild-type human SOD1 transgene do not.	0.52	1996	SOD1	21	31667299	G	C
rs121912438	19267424	6647	SOD1	umls:C1862939	BeFree	In the present study, we injected MSCs into the cerebrospinal fluid of symptomatic hSOD1(G93A) rats, a transgenic animal model of familial amyotrophic lateral sclerosis (ALS) expressing a mutated form of the human superoxide dismutase.	0.52	2009	SOD1	21	31667299	G	C
rs121912438	11730713	3976	LIF	umls:C1862939	BeFree	Leukemia inhibitory factor by systemic administration rescues spinal motor neurons in the SOD1 G93A murine model of familial amyotrophic lateral sclerosis.	0.000542884	2001	SOD1	21	31667299	G	C
rs121912438	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667299	G	C
rs121912438	15738401	6647	SOD1	umls:C1862939	BeFree	In the presence of several of these molecules, A4V and other FALS-linked SOD1 mutants such as G93A and G85R behaved similarly to wild-type SOD1, suggesting that these compounds could be leads toward effective therapeutics against FALS.	0.52	2005	SOD1	21	31667299	G	C
rs121912438	19655787	6647	SOD1	umls:C1862939	BeFree	Using 1H-15N HSQC NMR spectroscopy, we have analyzed hydrogen exchange at the amide groups of wild-type (wt) CuZnSOD and the fALS-associated G93A SOD variant in their fully metalated states.	0.52	2009	SOD1	21	31667299	G	C
rs121912438	12915243	3976	LIF	umls:C1862939	BeFree	Behavioural and anatomical effects of systemically administered leukemia inhibitory factor in the SOD1(G93A G1H) mouse model of familial amyotrophic lateral sclerosis.	0.000542884	2003	SOD1	21	31667299	G	C
rs121912438	20816908	100506742	CASP12	umls:C1862939	BeFree	Although up-regulation of caspase-12 has been reported in G93A SOD1 transgenic mice, it is controversial whether similar mechanisms operate in human FALS.	0.000271442	2010	SOD1	21	31667299	G	C
rs121912438	12901835	6647	SOD1	umls:C1862939	BeFree	We report that the expression of mutant G93A copper/zinc superoxide dismutase (SOD1), associated with familial amyotrophic lateral sclerosis, specifically causes a decrease in MTT reduction rate and ATP levels and an increase in both cytosolic and mitochondrial reactive oxygen species (ROS) production in human neuroblastoma SH-SY5Y cells compared to cells overexpressing wild-type SOD1 and untransfected cells.	0.52	2003	SOD1	21	31667299	G	C
rs121912438	11922659	6647	SOD1	umls:C1862939	BeFree	Long-term (10-11 weeks) transplantation of hNT Neurons into the L(4)-L(5) segments of the ventral horn spinal cord of FALS(G93A) mice at 7 weeks of age (before onset of overt behavioral symptoms of disease) delayed the onset of motor dysfunction for at least 3 weeks.	0.52	2002	SOD1	21	31667299	G	C
rs121912438	16624679	6647	SOD1	umls:C1862939	BeFree	G93A Cu/Zn superoxide dismutase (SOD1), a human mutant SOD1 associated with familial amyotrophic lateral sclerosis, increased the toxicity of the mitochondrial toxin rotenone in the NSC-34 motoneuronal cell line.	0.52	2006	SOD1	21	31667299	G	C
rs121912438	9083002	6445	SGCG	umls:C1862939	BeFree	We reported that Cu,Zn-SOD can catalyze free radical generation and a FALS mutant, G93A, exhibits an enhanced free radical-generating activity, while its dismutation activity is identical to that of the wild-type enzyme (Yim, M. B., Kang, J.-H., Yim, H.-S., Kwak, H.-S., Chock, P. B., and Stadtman, E. R. (1996) Proc.	0.001900093	1997	SOD1	21	31667299	G	C
rs121912438	12531528	6647	SOD1	umls:C1862939	BeFree	In this study we have investigated the effects of over-expressing wild-type SOD1 and two mutant forms of SOD1 found in FALS, G93A and G93R, on cell survival using stably transfected neuronal cells.	0.52	2002	SOD1	21	31667299	G	C
rs121912438	11730713	6647	SOD1	umls:C1862939	BeFree	Leukemia inhibitory factor by systemic administration rescues spinal motor neurons in the SOD1 G93A murine model of familial amyotrophic lateral sclerosis.	0.52	2001	SOD1	21	31667299	G	C
rs121912438	12421599	6647	SOD1	umls:C1862939	BeFree	In transgenic mice carrying the G93A human mutation of Cu/Zn superoxide dismutase (SOD1), which provide a model of familial amyotrophic lateral sclerosis, we investigated, before the onset of symptoms, two parameters of the response of facial motoneurons to nerve transection, i.e.	0.52	2002	SOD1	21	31667299	G	C
rs121912438	19495690	6647	SOD1	umls:C1862939	BeFree	Lentivirus and adeno-associated virus have been used to knockdown levels of mutated superoxide dismutase 1 (SOD1) in the G93A SOD1 mouse model of familial amyotrophic lateral sclerosis (fALS) to result in beneficial therapeutic outcomes.	0.52	2009	SOD1	21	31667299	G	C
rs121912438	18539273	6647	SOD1	umls:C1862939	BeFree	In parallel, MSCs derived from the bone marrow of a transgenic rat model of familial ALS (hSOD1(G93A)) were also characterised.	0.52	2008	SOD1	21	31667299	G	C
rs121912438	16045483	6647	SOD1	umls:C1862939	BeFree	Point mutations such as G93A and A4V in the human Cu/Zn-superoxide dismutase gene (hSOD1) cause familial amyotrophic lateral sclerosis (fALS).	0.52	2005	SOD1	21	31667299	G	C
rs121912438	14648077	2876	GPX1	umls:C1862939	BeFree	To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.	0.000271442	2004	SOD1	21	31667299	G	C
rs121912438	14648077	6647	SOD1	umls:C1862939	BeFree	To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.	0.52	2004	SOD1	21	31667299	G	C
rs121912438	17603925	6647	SOD1	umls:C1862939	BeFree	The paper by Butterfield and colleagues reporting the use of redox proteomics to identify oxidatively modified proteins in the spinal cord in the G93A-SOD1 mouse model of familial amyotrophic lateral sclerosis was identified by the SCOPUS science literature information system to be one of the top 20 downloaded papers for 2005-2006 in Free Radical Biology and Medicine.	0.52	2007	SOD1	21	31667299	G	C
rs121912438	12060716	3315	HSPB1	umls:C1862939	BeFree	Herein, we demonstrate that the entry of SOD1 into mitochondria depends on demetallation and that heat shock proteins (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1 (G37R, G41D, or G93A), while having no effect on wild-type SOD1.	0.000271442	2002	SOD1	21	31667299	G	C
rs121912438	12915243	6647	SOD1	umls:C1862939	BeFree	Behavioural and anatomical effects of systemically administered leukemia inhibitory factor in the SOD1(G93A G1H) mouse model of familial amyotrophic lateral sclerosis.	0.52	2003	SOD1	21	31667299	G	C
rs121912438	9052802	6647	SOD1	umls:C1862939	BeFree	High levels of familial Amyotrophic Lateral Sclerosis (ALS)-linked SOD1 mutants G93A and G37R were previously shown to mediate disease in mice through an acquired toxic property.	0.52	1997	SOD1	21	31667299	G	C
rs121912439	9008494	6647	SOD1	umls:C1862939	BeFree	Prognosis in familial amyotrophic lateral sclerosis: progression and survival in patients with glu100gly and ala4val mutations in Cu,Zn superoxide dismutase.	0.52	1997	SOD1	21	31667320	A	G
rs121912439	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667320	A	G
rs121912440	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667337	C	G
rs121912440	22647583	6647	SOD1	umls:C1862939	BeFree	Neurogenic bladder, sensory impairment, and degeneration of the hypothalamus and thalamus might be specific features in patients with familial amyotrophic lateral sclerosis with L106V mutation in the SOD1 gene.	0.52	2012	SOD1	21	31667337	C	G
rs121912441	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667359	T	C
rs121912442	9008494	6647	SOD1	umls:C1862939	BeFree	Prognosis in familial amyotrophic lateral sclerosis: progression and survival in patients with glu100gly and ala4val mutations in Cu,Zn superoxide dismutase.	0.52	1997	SOD1;LOC102724449	21	31659783	C	T
rs121912442	7951249	6647	SOD1	umls:C1862939	BeFree	A frequent ala 4 to val superoxide dismutase-1 mutation is associated with a rapidly progressive familial amyotrophic lateral sclerosis.	0.52	1994	SOD1;LOC102724449	21	31659783	C	T
rs121912442	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1;LOC102724449	21	31659783	C	T
rs121912443	10461909	6647	SOD1	umls:C1862939	BeFree	We have investigated the response to oxidative stress in a model system obtained by stable transfection of the human neuroblastoma cell line SH-SY5Y with plasmids directing constitutive expression of either wild-type human Cu,Zn superoxide dismutase or a mutant of this enzyme (H46R) associated with familial amyotrophic lateral sclerosis.	0.52	1999	SOD1	21	31663857	A	G
rs121912443	15465081	6647	SOD1	umls:C1862939	BeFree	Familial amyotrophic lateral sclerosis with His46Arg mutation in Cu/Zn superoxide dismutase presenting characteristic clinical features and Lewy body-like hyaline inclusions.	0.52	2004	SOD1	21	31663857	A	G
rs121912443	11997070	6647	SOD1	umls:C1862939	BeFree	Clinical features and neuropathological findings of familial amyotrophic lateral sclerosis with a His46Arg mutation in Cu/Zn superoxide dismutase.	0.52	2002	SOD1	21	31663857	A	G
rs121912443	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31663857	A	G
rs121912443	14648077	6647	SOD1	umls:C1862939	BeFree	To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.	0.52	2004	SOD1	21	31663857	A	G
rs121912443	7836951	6647	SOD1	umls:C1862939	BeFree	Familial amyotrophic lateral sclerosis (ALS) in Japan associated with H46R mutation in Cu/Zn superoxide dismutase gene: a possible new subtype of familial ALS.	0.52	1994	SOD1	21	31663857	A	G
rs121912443	14517684	6647	SOD1	umls:C1862939	BeFree	Clinical and pathological studies of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R mutation in large Japanese families.	0.52	2003	SOD1	21	31663857	A	G
rs121912443	16563356	6647	SOD1	umls:C1862939	BeFree	To identify the conversion of SOD1 from a normally soluble form to insoluble aggregates, we investigated the change of SOD1 solubility with aging in fALS-linked H46R SOD1 transgenic mice.	0.52	2006	SOD1	21	31663857	A	G
rs121912443	14648077	2876	GPX1	umls:C1862939	BeFree	To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.	0.000271442	2004	SOD1	21	31663857	A	G
rs121912443	15840828	6647	SOD1	umls:C1862939	BeFree	Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46Arg.	0.52	2005	SOD1	21	31663857	A	G
rs121912443	11701756	6647	SOD1	umls:C1862939	BeFree	In a recent work, we have observed that calcineurin activity is depressed in two models for familial amyotrophic lateral sclerosis (FALS) associated with mutations of the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1), namely in neuroblastoma cells expressing either SOD1 mutant G93A or mutant H46R and in brain areas from G93A transgenic mice.	0.52	2001	SOD1	21	31663857	A	G
rs121912443	17549011	6647	SOD1	umls:C1862939	BeFree	Human familial amyotrophic lateral sclerosis with an H46R mutant Cu/Zn superoxide dismutase (SOD1) gene is characterized by initial muscle weakness and atrophy in the legs and a very long-term clinical course (approximately 15 years).	0.52	2007	SOD1	21	31663857	A	G
rs121912444	8830861	6647	SOD1	umls:C1862939	BeFree	Instability of mutant Cu/Zn superoxide dismutase (Ala4Thr) associated with familial amyotrophic lateral sclerosis.	0.52	1996	SOD1;LOC102724449	21	31659782	G	A
rs121912444	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1;LOC102724449	21	31659782	G	A
rs121912446	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31668547	T	C
rs121912447	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31668549	G	A
rs121912448	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1;LOC102724449	21	31659789	G	T
rs121912449	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31668568	T	C
rs121912450	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1;LOC102724449	21	31659833	G	A
rs121912451	16105836	6647	SOD1	umls:C1862939	BeFree	S134N copper-zinc superoxide dismutase (SOD1) is one of the many mutant SOD1 proteins known to cause familial amyotrophic lateral sclerosis.	0.52	2005	SOD1	21	31668517	G	A
rs121912451	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31668517	G	A
rs121912452	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667271	T	C,G
rs121912453	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1;LOC102724449	21	31659818	G	A
rs121912454	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31668493	T	A
rs121912455	21084099	6647	SOD1	umls:C1862939	BeFree	Involvement of Onuf's nucleus may be a characteristic pathological feature in FALS with Gly72Ser mutation in the SOD1 gene.	0.52	2011	SOD1	21	31666496	G	A
rs121912455	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31666496	G	A
rs121912456	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1;LOC102724449	21	31659806	G	C
rs121912457	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31663854	T	G
rs121912458	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667260	A	G
rs140591214	14648077	6647	SOD1	umls:C1862939	BeFree	To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.	0.52	2004	PRRX2;PRRX2-AS1	9	129720663	C	G
rs140591214	14648077	2876	GPX1	umls:C1862939	BeFree	To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations.	0.000271442	2004	PRRX2;PRRX2-AS1	9	129720663	C	G
rs373584770	15208263	836	CASP3	umls:C1862939	BeFree	Activation of caspase-1 and caspase-3 is observed also in neuroblastoma lines expressing other fALS-SOD1s (G37R, G85R, and I113T) cocultured with glioblastoma lines expressing the corresponding mutant enzymes.	0.000542884	2004	CASP1	11	105030337	G	A
rs373584770	15208263	834	CASP1	umls:C1862939	BeFree	Activation of caspase-1 and caspase-3 is observed also in neuroblastoma lines expressing other fALS-SOD1s (G37R, G85R, and I113T) cocultured with glioblastoma lines expressing the corresponding mutant enzymes.	0.120542884	2004	CASP1	11	105030337	G	A
rs376557198	21752789	80818	ZNF436	umls:C1862939	BeFree	To better mimic human amyotrophic lateral sclerosis, we generated transgenic mice that exhibit moderate and ubiquitous expression of transactive response DNA-binding protein 43 species using genomic fragments that encode wild-type human transactive response DNA-binding protein 43 or familial amyotrophic lateral sclerosis-linked mutant transactive response DNA-binding protein 43 (G348C) and (A315T).	0.000542884	2011	ZNF436	1	23363034	G	C
rs387906789	23349634	7415	VCP	umls:C1862939	BeFree	This stimulatory effect was lost when we used VCP mutants (R155H, R159G, and R191Q) known to cause Inclusion Body Myopathy with Paget's disease of bone and Fronto-temporal Dementia (IBMPFD) and/or familial Amyotrophic Lateral Sclerosis (ALS).	0.003528744	2013	VCP	9	35065352	G	C,A
rs74315431	20377183	4477	MSMB	umls:C1862939	BeFree	The Pro56Ser mutation in the human VAPB MSP domain causes a familial amyotrophic lateral sclerosis.	0.000542884	2010	VAPB	20	58418318	C	T
rs74315431	20377183	9217	VAPB	umls:C1862939	BeFree	The Pro56Ser mutation in the human VAPB MSP domain causes a familial amyotrophic lateral sclerosis.	0.000814326	2010	VAPB	20	58418318	C	T
rs74315431	20377183	89782	LMLN	umls:C1862939	BeFree	The Pro56Ser mutation in the human VAPB MSP domain causes a familial amyotrophic lateral sclerosis.	0.000542884	2010	VAPB	20	58418318	C	T
rs74315431	19183264	9217	VAPB	umls:C1862939	BeFree	A point mutation (P56S) in the vapb gene encoding an endoplasmic reticulum (ER)-integrated membrane protein [vesicle-associated membrane protein-associated protein B (VAPB)] causes autosomal-dominant amyotrophic lateral sclerosis.	0.000814326	2009	VAPB	20	58418318	C	T
rs74315431	20377183	84000	TMPRSS13	umls:C1862939	BeFree	The Pro56Ser mutation in the human VAPB MSP domain causes a familial amyotrophic lateral sclerosis.	0.000542884	2010	VAPB	20	58418318	C	T
rs74315431	20377183	4485	MST1	umls:C1862939	BeFree	The Pro56Ser mutation in the human VAPB MSP domain causes a familial amyotrophic lateral sclerosis.	0.000542884	2010	VAPB	20	58418318	C	T
rs74315452	10567054	6647	SOD1	umls:C1862939	BeFree	These data suggest that this case might have been different from an example of fALS with Ile 113 Thr mutation in the SOD1 gene.	0.52	1999	SOD1	21	31667356	T	C
rs74315452	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667356	T	C
rs74315452	10593307	6647	SOD1	umls:C1862939	BeFree	Accumulation of neurofilaments and SOD1-immunoreactive products in a patient with familial amyotrophic lateral sclerosis with I113T SOD1 mutation.	0.52	1999	SOD1	21	31667356	T	C
rs80265967	12710511	6647	SOD1	umls:C1862939	BeFree	The Aspartate-90-Alanine (D90A) mutation on SOD-1 gene, the only known change causing recessive familial amyotrophic lateral sclerosis (FALS), is associated with a uniform phenotype characterized by slowly ascending paresis and long survival.	0.52	2002	SOD1	21	31667290	A	C
rs80265967	9749537	6647	SOD1	umls:C1862939	BeFree	Expression, purification, and characterization of a familial amyotrophic lateral sclerosis-associated D90A Cu,Zn-superoxide dismutase mutant.	0.52	1998	SOD1	21	31667290	A	C
rs80265967	9891852	6647	SOD1	umls:C1862939	BeFree	The free radical-generating function of a familial amyotrophic lateral sclerosis-associated D90A Cu,Zn-superoxide dismutase mutant.	0.52	1998	SOD1	21	31667290	A	C
rs80265967	10809943	6647	SOD1	umls:C1862939	BeFree	Coexistence of dominant and recessive familial amyotrophic lateral sclerosis with the D90A Cu,Zn superoxide dismutase mutation within the same country.	0.52	2000	SOD1	21	31667290	A	C
rs80265967	NA	6647	SOD1	umls:C1862939	CLINVAR	NA	0.52	NA	SOD1	21	31667290	A	C
rs80265967	18301754	6647	SOD1	umls:C1862939	UNIPROT	SOD1 and amyotrophic lateral sclerosis: mutations and oligomerization.	0.52	2008	SOD1	21	31667290	A	C
rs80356730	20154440	23435	TARDBP	umls:C1862939	BeFree	TDP-43 M337V mutation in familial amyotrophic lateral sclerosis in Japan.	0.087600372	2010	TARDBP	1	11022418	A	G
rs80356730	24466128	23435	TARDBP	umls:C1862939	BeFree	To examine the contribution of these potentially toxic mechanisms in vivo, we generated transgenic mice expressing human TDP-43 containing the familial amyotrophic lateral sclerosis-linked M337V mutation and identified two lines that developed neurological phenotypes of differing severity and progression.	0.087600372	2013	TARDBP	1	11022418	A	G

GWASdb Annotation(Total Genotypes:0)
(Waiting for update.)

GWASdb Snp Trait(Total Genotypes:0)
(Waiting for update.)

Mapped by lexical matching(Total Items:0)
(Waiting for update.)

Mapped by homologous gene(Total Items:0)
(Waiting for update.)

Chemical(Total Drugs:3)
CUI	ChemicalName	ChemicalID	CasRN	DiseaseName	DiseaseID	DirectEvidence	PubMedIDs
C1862939	gabapentin	C040029	60142-96-3	amyotrophic lateral sclerosis 1	MESH:C531617	therapeutic	8967745
C1862939	riluzole	D019782	1744-22-5	amyotrophic lateral sclerosis 1	MESH:C531617	therapeutic	8967745
C1862939	vitamin e	D014810	1406-18-4	amyotrophic lateral sclerosis 1	MESH:C531617	therapeutic	8967745

FDA approved drug and dosage information(Total Drugs:7)
DiseaseID	Drug_name	active_ingredients	strength	Dosage Form/Route	Marketing Status	TE code	RLD	RS
MESH:C531617	neurontin	gabapentin	100MG	CAPSULE;ORAL	Prescription	AB	Yes	No
MESH:C531617	neurontin	gabapentin	600MG	TABLET;ORAL	Prescription	AB	Yes	No
MESH:C531617	neurontin	gabapentin	250MG/5ML	SOLUTION;ORAL	Prescription	AA	Yes	Yes
MESH:C531617	neurontin	gabapentin	0	SOLUTION; ORAL	Prescription	None	No	No
MESH:C531617	neurontin	gabapentin	600MG	TABLET; ORAL	Prescription	None	No	No
MESH:C531617	neurontin	gabapentin	800MG	CAPSULE; ORAL	Prescription	None	No	No
MESH:C531617	neurontin	gabapentin	250MG/5ML	SOLUTION; ORAL	Prescription	None	No	No

FDA labeling changes(Total Drugs:7)
DiseaseID	Pediatric_Labeling_Date	Trade_Name	Generic_Name_or_Proper_Name	Indications Studied	Label Changes Summary	Product Labeling	BPCA(B)	PREA(P)	BPCA(B) and PREA(P)	Pediatric Rule (R)	Sponsor	Pediatric Exclusivity Granted Date	NNPS
MESH:C531617	12/10/2000	neurontin	gabapentin	Adjunctive therapy in the treatment of partial seizures	Safety and effectiveness established down to 3 years Neuropsychiatric AE's identified in 3-12 year olds Oral clearance normalized per body weight increased in children	Labeling	B	-	-	-	Parke-Davis	2/2/2000	FALSE'
MESH:C531617	12/10/2000	neurontin	gabapentin	Adjunctive therapy in the treatment of partial seizures	Safety and effectiveness established down to 3 years Neuropsychiatric AE's identified in 3-12 year olds Oral clearance normalized per body weight increased in children	Labeling	B	-	-	-	Parke-Davis	2/2/2000	FALSE'
MESH:C531617	12/10/2000	neurontin	gabapentin	Adjunctive therapy in the treatment of partial seizures	Safety and effectiveness established down to 3 years Neuropsychiatric AE's identified in 3-12 year olds Oral clearance normalized per body weight increased in children	Labeling	B	-	-	-	Parke-Davis	2/2/2000	FALSE'
MESH:C531617	12/10/2000	neurontin	gabapentin	Adjunctive therapy in the treatment of partial seizures	Safety and effectiveness established down to 3 years Neuropsychiatric AE's identified in 3-12 year olds Oral clearance normalized per body weight increased in children	Labeling	B	-	-	-	Parke-Davis	2/2/2000	FALSE'
MESH:C531617	12/10/2000	neurontin	gabapentin	Adjunctive therapy in the treatment of partial seizures	Safety and effectiveness established down to 3 years Neuropsychiatric AE's identified in 3-12 year olds Oral clearance normalized per body weight increased in children	Labeling	B	-	-	-	Parke-Davis	2/2/2000	FALSE'
MESH:C531617	12/10/2000	neurontin	gabapentin	Adjunctive therapy in the treatment of partial seizures	Safety and effectiveness established down to 3 years Neuropsychiatric AE's identified in 3-12 year olds Oral clearance normalized per body weight increased in children	Labeling	B	-	-	-	Parke-Davis	2/2/2000	FALSE'
MESH:C531617	12/10/2000	neurontin	gabapentin	Adjunctive therapy in the treatment of partial seizures	Safety and effectiveness established down to 3 years Neuropsychiatric AE's identified in 3-12 year olds Oral clearance normalized per body weight increased in children	Labeling	B	-	-	-	Parke-Davis	2/2/2000	FALSE'