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	acute intermittent porphyria

Disease ID	15
Disease	acute intermittent porphyria
Definition	An autosomal dominant porphyria that is due to a deficiency of HYDROXYMETHYLBILANE SYNTHASE in the LIVER, the third enzyme in the 8-enzyme biosynthetic pathway of HEME. Clinical features are recurrent and life-threatening neurologic disturbances, ABDOMINAL PAIN, and elevated level of AMINOLEVULINIC ACID and PORPHOBILINOGEN in the urine.
Synonym	acute intermittent porphyria (disorder) acute intermittent porphyria (disorder) [ambiguous] acute intermittent porphyrias acute porphyria acute porphyrias aip aip - acute intermittent porphyria intermittent acute porphyria intermittent acute porphyria syndrome intermittent porphyria, acute intermittent porphyrias, acute porphyria acute porphyria acute intermittent porphyria intermittent acute porphyria, acute porphyria, acute intermittent porphyria, acute intermittent [disease/finding] porphyrias, acute porphyrias, acute intermittent pyrroloporphyria swedish porphyria
Orphanet	ORPHANET:79276
OMIM	OMIM:176000 OMIM:609183
DOID	DOID:3890 DOID:3133 DOID:2800
UMLS	C0162565
MeSH	D017118
SNOMED-CT	SNOMEDCT_US_2016_09_01:234422006
Comorbidity	UMLS \| Disease \| Sentences' Count(Total Sentences:14) C0162565 \| acute intermittent porphyria \| 8 C0032708 \| porphyria \| 2 C0155320 \| cortical blindness \| 1 C0022658 \| kidney disease \| 1 C0026769 \| multiple sclerosis \| 1 C0162565 \| acute porphyria \| 1 C0442874 \| neuropathy \| 1 C0598608 \| hyperhomocysteinemia \| 1 C1145670 \| respiratory failure \| 1 C0014130 \| hormonal imbalance \| 1 C0497327 \| dementia \| 1 C0022661 \| chronic kidney disease \| 1 C0162565 \| acute porphyrias \| 1 C0032708 \| porphyrias \| 1
Curated Gene	Entrez_id \| Symbol \| Resource(Total Genes:2) 3145 \| HMBS \| CLINVAR;CTD_human;ORPHANET;UNIPROT 54998 \| AURKAIP1 \| OMIM
Inferring Gene	Entrez_id \| Symbol \| Resource(Total Genes:1) 3145 \| HMBS \| CIPHER;CTD_human
Text Mined Gene	Entrez_id \| Symbol \| Score \| Resource(Total Genes:83) 23456 \| ABCB10 \| 1.535 \| DISEASES 210 \| ALAD \| 5.376 \| DISEASES 210 \| ALAD \| 5.324 \| DISEASES 212 \| ALAS2 \| 5.694 \| DISEASES 212 \| ALAS2 \| 2.602 \| DISEASES 537 \| ATP6AP1 \| 2.579 \| DISEASES 537 \| ATP6AP1 \| 1.878 \| DISEASES 551 \| AVP \| 3.838 \| DISEASES 551 \| AVP \| 3.494 \| DISEASES 631 \| BFSP1 \| 1.835 \| DISEASES 641 \| BLM \| 1.521 \| DISEASES 1369 \| CPN1 \| 1.372 \| DISEASES 1504 \| CTRB1 \| 2.194 \| DISEASES 1543 \| CYP1A1 \| 1.001 \| DISEASES 1544 \| CYP1A2 \| 4.031 \| DISEASES 1553 \| CYP2A13 \| 1.317 \| DISEASES 1555 \| CYP2B6 \| 3.6 \| DISEASES 1576 \| CYP3A4 \| 1.44 \| DISEASES 1798 \| DPAGT1 \| 1.314 \| DISEASES 57119 \| EPPIN \| 2.185 \| DISEASES 2235 \| FECH \| 7.639 \| DISEASES 2235 \| FECH \| 3.719 \| DISEASES 8443 \| GNPAT \| 1.563 \| DISEASES 2880 \| GPX5 \| 1.778 \| DISEASES 257202 \| GPX6 \| 1.79 \| DISEASES 23426 \| GRIP1 \| 1.634 \| DISEASES 3030 \| HADHA \| 1.676 \| DISEASES 3077 \| HFE \| 5.646 \| DISEASES 3077 \| HFE \| 1.004 \| DISEASES 148738 \| HFE2 \| 2.064 \| DISEASES 3105 \| HLA-A \| 1.291 \| DISEASES 3240 \| HP \| 1.827 \| DISEASES 338376 \| IFNE \| 1.789 \| DISEASES 387755 \| INSC \| 2.266 \| DISEASES 387755 \| INSC \| 2.01 \| DISEASES 55656 \| INTS8 \| 2.996 \| DISEASES 55656 \| INTS8 \| 2.294 \| DISEASES 102723508 \| KANTR \| 1.576 \| DISEASES 102723508 \| KANTR \| 1.174 \| DISEASES 3980 \| LIG3 \| 1.107 \| DISEASES 4094 \| MAF \| 1.091 \| DISEASES 4157 \| MC1R \| 2.482 \| DISEASES 4540 \| MT-ND5 \| 1.442 \| DISEASES 8131 \| NPRL3 \| 2.35 \| DISEASES 54681 \| P4HTM \| 1.342 \| DISEASES 5091 \| PC \| 1.712 \| DISEASES 10611 \| PDLIM5 \| 1.684 \| DISEASES 5178 \| PEG3 \| 1.253 \| DISEASES 5313 \| PKLR \| 1.042 \| DISEASES 5447 \| POR \| 1.162 \| DISEASES 5498 \| PPOX \| 7.056 \| DISEASES 5498 \| PPOX \| 5.842 \| DISEASES 80324 \| PUS1 \| 1.88 \| DISEASES 6014 \| RIT2 \| 1.522 \| DISEASES 6906 \| SERPINA7 \| 2.059 \| DISEASES 6906 \| SERPINA7 \| 1.357 \| DISEASES 5272 \| SERPINB9 \| 1.15 \| DISEASES 23410 \| SIRT3 \| 1.171 \| DISEASES 23408 \| SIRT5 \| 1.569 \| DISEASES 23408 \| SIRT5 \| 1.313 \| DISEASES 6565 \| SLC15A2 \| 2.453 \| DISEASES 6565 \| SLC15A2 \| 1.752 \| DISEASES 51312 \| SLC25A37 \| 3.454 \| DISEASES 8803 \| SUCLA2 \| 1.568 \| DISEASES 6999 \| TDO2 \| 3.238 \| DISEASES 6999 \| TDO2 \| 2.675 \| DISEASES 26136 \| TES \| 1.396 \| DISEASES 54790 \| TET2 \| 1.719 \| DISEASES 7018 \| TF \| 3.658 \| DISEASES 7019 \| TFAM \| 1.083 \| DISEASES 7037 \| TFRC \| 1.98 \| DISEASES 51337 \| THEM6 \| 2.074 \| DISEASES 51337 \| THEM6 \| 1.373 \| DISEASES 51643 \| TMBIM4 \| 1.234 \| DISEASES 84000 \| TMPRSS13 \| 2.355 \| DISEASES 84000 \| TMPRSS13 \| 1.653 \| DISEASES 7225 \| TRPC6 \| 1.179 \| DISEASES 10194 \| TSHZ1 \| 1.98 \| DISEASES 10194 \| TSHZ1 \| 1.279 \| DISEASES 7360 \| UGP2 \| 1.707 \| DISEASES 7390 \| UROS \| 6.583 \| DISEASES 7390 \| UROS \| 6.354 \| DISEASES 23038 \| WDTC1 \| 1.457 \| DISEASES
Locus	Symbol \| Locus(Total Locus:1) HMBS \| 11q23.3

Disease ID	15
Disease	acute intermittent porphyria
Integrated Phenotype	HPO \| Name(Total Integrated Phenotypes:29) HP:0012086 \| Abnormal urinary color HP:0002385 \| Paraparesis HP:0002019 \| Constipation HP:0002027 \| Abdominal pain HP:0001824 \| Weight loss HP:0000083 \| Renal insufficiency HP:0002829 \| Arthralgia HP:0003401 \| Paresthesia HP:0003326 \| Myalgia HP:0000016 \| Urinary retention HP:0001254 \| Lethargy HP:0002902 \| Hyponatremia HP:0000822 \| Hypertension HP:0002017 \| Nausea and vomiting HP:0100735 \| Hypertensive crisis HP:0000739 \| Anxiety HP:0000708 \| Behavioral abnormality HP:0001250 \| Seizures HP:0000975 \| Hyperhidrosis HP:0001402 \| Hepatocellular carcinoma HP:0011675 \| Arrhythmia HP:0003077 \| Hyperlipidemia HP:0006597 \| Diaphragmatic paralysis HP:0001324 \| Muscle weakness HP:0000738 \| Hallucinations HP:0000716 \| Depression HP:0100785 \| Insomnia HP:0006824 \| Cranial nerve paralysis HP:0002039 \| Anorexia
Text Mined Phenotype	HPO \| Name \| Sentences' Count(Total Phenotypes:7) HP:0001298 \| Encephalopathy \| 3 HP:0012622 \| Chronic kidney disease \| 1 HP:0002878 \| Respiratory failure \| 1 HP:0002308 \| Chiari malformation \| 1 HP:0100704 \| Cortical visual impairment \| 1 HP:0030756 \| Erythrodontia \| 1 HP:0000726 \| Dementia \| 1

Disease ID	15
Disease	acute intermittent porphyria
Manually Symptom	UMLS \| Name(Total Manually Symptoms:56) C2712322 \| tachycardia C2127436 \| ascending paralysis C1963138 \| hypertension C1521736 \| parkinson's disease C1512411 \| hepatocellular carcinoma C1456784 \| paranoid psychosis C1403038 \| lipoproteinemia C1384514 \| primary aldosteronism C1145670 \| respiratory failure C0878544 \| cardiomyopathy C0752303 \| urological manifestations C0599750 \| hormone deficiency C0518988 \| dental abscess C0442874 \| neuropathy C0345904 \| liver cancer C0341697 \| renal impairment C0311292 \| porphobilinogen deaminase deficiency C0271728 \| secondary hyperaldosteronism C0270795 \| monoparesis C0259749 \| autonomic neuropathy C0235031 \| neurologic symptoms C0233777 \| hallucinosis C0233401 \| psychiatric symptoms C0221773 \| hyperamylasemia C0221505 \| brain lesions C0206620 \| cystic lymphangioma C0155320 \| cortical blindness C0152025 \| polyneuropathy C0086132 \| depressive symptoms C0041349 \| tubulointerstitial nephritis C0038220 \| status epilepticus C0036572 \| seizures C0035258 \| restless legs syndrome C0035229 \| respiratory insufficiency C0035204 \| respiratory disorders C0032587 \| polyradiculoneuropathy C0030312 \| bone marrow failure C0029124 \| optic atrophy C0027765 \| neurologic disorders C0024141 \| systemic lupus erythematosus C0023467 \| acute myelogenous leukemia C0022661 \| chronic renal failure C0022658 \| renal disease C0021141 \| inappropriate adh syndrome C0020625 \| hyponatremia C0020550 \| hyperthyroidism C0020514 \| hyperprolactinemia C0020459 \| hyperinsulinemia C0020437 \| hypercalcaemia C0014548 \| generalized seizure disorders C0014544 \| epileptic seizures C0014544 \| epilepsy C0013363 \| dysautonomia C0004936 \| mental disorders C0001339 \| acute pancreatitis C0000737 \| abdominal pain
Text Mined Symptom	UMLS \| Name \| Sentences' Count(Total Symptoms:3) C0155320 \| cortical blindness \| 1 C1145670 \| respiratory failure \| 1 C0442874 \| neuropathy \| 1

Manually Genotype(Total Manually Genotypes:1)
Gene	Mutation	DOI	Article Title
HMBS	NM_000190, c.427G>A (p.V143M)	doi:10.1038/gim.2015.186	Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy

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

All Snps(Total Genotypes:32)
snpId	pubmedId	geneId	geneSymbol	diseaseId	sourceId	sentence	score	Year	geneSymbol_dbSNP	CHROMOSOME	POS	REF	ALT
rs118204094	19656453	3145	HMBS	umls:C0162565	BeFree	Evidence for an ancestral founder of the common R116W mutation in the hydroxymethylbilane synthase gene in acute intermittent porphyria in The Netherlands.	0.632518213	2009	HMBS	11	119089991	C	T
rs118204094	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119089991	C	T
rs118204095	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119091414	G	A,T
rs118204096	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119091432	G	A
rs118204097	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119090230	C	T
rs118204098	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119090213	G	A
rs118204099	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092486	T	G
rs118204100	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119091507	G	A
rs118204100	11202057	3145	HMBS	umls:C0162565	BeFree	The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population-based study.	0.632518213	2000	HMBS	11	119091507	G	A
rs118204101	11202057	3145	HMBS	umls:C0162565	BeFree	The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population-based study.	0.632518213	2000	HMBS	11	119091413	C	T
rs118204101	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119091413	C	T
rs118204103	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119088298	G	A
rs118204104	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119088638	G	A
rs118204105	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119088647	C	A
rs118204106	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119089084	G	T
rs118204107	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119089747	G	A
rs118204107	10494093	3145	HMBS	umls:C0162565	BeFree	Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation.	0.632518213	1999	HMBS	11	119089747	G	A
rs118204108	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119091444	T	G
rs118204109	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119091515	C	T
rs118204110	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092419	G	A
rs118204111	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092491	T	C
rs118204112	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092500	G	A
rs118204113	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092506	G	A
rs118204114	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092507	C	T
rs118204115	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092518	C	A
rs118204116	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092159	G	A
rs118204117	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119092958	G	A
rs118204117	10782018	3145	HMBS	umls:C0162565	BeFree	Identification of a prevalent nonsense mutation (W283X) and two novel mutations in the porphobilinogen deaminase gene of Swiss patients with acute intermittent porphyria.	0.632518213	2000	HMBS	11	119092958	G	A
rs118204119	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119089248	T	C
rs118204120	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119090212	C	T
rs34413634	NA	3145	HMBS	umls:C0162565	CLINVAR	NA	0.632518213	NA	HMBS	11	119091497	C	T
rs34413634	16211556	3145	HMBS	umls:C0162565	UNIPROT	Direct sequencing of genomic DNA samples of 11 unrelated Russian AIP patients, 32 of their relatives and 50 healthy controls from northwestern Russia including Saint Petersburg revealed nine mutations in the HMBS gene.	0.632518213	2005	HMBS	11	119091497	C	T

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

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

Mapped by lexical matching(Total Items:7)
HP ID	HP Name	MP ID	MP Name	Annotation
HP:0001402	Hepatocellular carcinoma	MP:0010367	increased spindle cell carcinoma incidence	greater than the expected number of a highly malignant variant of squamous cell carcinoma, occurring in a specific population in a given time period; spindle cell carcinoma shows biphasic proliferation of conventional SCC component and malignant spindle s
HP:0000083	Renal insufficiency	MP:0003335	exocrine pancreatic insufficiency	inadequate synthesis and/or secretion of digestive enzymes by the exocrine portion of the pancreas, usually due to loss of acinar tissue from idiopathic atrophy or acute or chronic inflammation, causing maldigestion and malabsorption of nutrients
HP:0001324	Muscle weakness	MP:0000746	weakness	state of being infirm or less strong than normal
HP:0006824	Cranial nerve paralysis	MP:0006303	abnormal retinal nerve fiber layer morphology	any structural anomaly of the layer of the retina formed by expansion of the fibers of the optic nerve
HP:0002017	Nausea and vomiting	MP:0010426	abnormal heart and great artery attachment	any anomaly in the in the position or pattern of the connection site of the heart to any of the great arteries, including the pulmonary artery and aorta
HP:0006597	Diaphragmatic paralysis	MP:0000755	hindlimb paralysis	loss of power of voluntary movement in the muscles of the hindlimb through injury or disease of it or its nerve supply
HP:0001824	Weight loss	MP:0005114	premature hair loss	release of fur at an earlier than expected time

Mapped by homologous gene(Total Items:28)
HP ID	HP Name	MP ID	MP Name	Annotation
HP:0003077	Hyperlipidemia	MP:0020216	decreased circulating complement protein level	less than normal levels of the serum proteins that act sequentially to allow for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes
HP:0000739	Anxiety	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0011675	Arrhythmia	MP:0020309	increased creatine kinase activity	increased ability of to catalyze the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+).
HP:0001250	Seizures	MP:3000003	abnormal Ebner's gland morphology	any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l
HP:0000708	Behavioral abnormality	MP:0020316	decreased vascular endothelial cell proliferation	decrease in the expansion rate of any vascular endothelial cell population by cell division
HP:0002385	Paraparesis	MP:0013781	abnormal mammary gland luminal epithelium morphology	any structural anomaly of the inner cell layer of the mammary epithelium bilayer that lines the luminal surface of mammary gland ducts and alveoli; luminal cells have only limited contact with the underlying basement membrane and surrounding connective ti
HP:0003401	Paresthesia	MP:0014185	cerebellum atrophy	acquired diminution of the size of the cerebellum associated with wasting as from death and reabsorption of cells, diminished cellular proliferation, decreased cellular volume, pressure, ischemia, malnutrition, reduced function or malfunction, or hormonal
HP:0100735	Hypertensive crisis	MP:0011414	erythruria	passage of red colored urine
HP:0000822	Hypertension	MP:0020216	decreased circulating complement protein level	less than normal levels of the serum proteins that act sequentially to allow for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes
HP:0006597	Diaphragmatic paralysis	MP:0014074	increased brain glycogen level	greater than the normal concentration of a readily converted carbohydrate reserve in brain
HP:0002017	Nausea and vomiting	MP:0020220	decreased tear production	decreased production of the amount of fluid produced in the eye
HP:0001324	Muscle weakness	MP:0020309	increased creatine kinase activity	increased ability of to catalyze the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+).
HP:0002039	Anorexia	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone
HP:0000975	Hyperhidrosis	MP:0020187	altered susceptibility to prion infection	altered likelihood that an organism will develop ill effects from the small proteinaceous infectious particles which are resistant to inactivation by procedures that modify nucleic acids and which contain an abnormal isoform of a cellular protein that is
HP:0001824	Weight loss	MP:0020220	decreased tear production	decreased production of the amount of fluid produced in the eye
HP:0002829	Arthralgia	MP:0020154	impaired humoral immune response	impaired response of the immune system that mediates secreted antibodies produced in B cells
HP:0000083	Renal insufficiency	MP:0020316	decreased vascular endothelial cell proliferation	decrease in the expansion rate of any vascular endothelial cell population by cell division
HP:0002027	Abdominal pain	MP:0020220	decreased tear production	decreased production of the amount of fluid produced in the eye
HP:0001254	Lethargy	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone
HP:0003326	Myalgia	MP:0020309	increased creatine kinase activity	increased ability of to catalyze the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+).
HP:0100785	Insomnia	MP:0020187	altered susceptibility to prion infection	altered likelihood that an organism will develop ill effects from the small proteinaceous infectious particles which are resistant to inactivation by procedures that modify nucleic acids and which contain an abnormal isoform of a cellular protein that is
HP:0000738	Hallucinations	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0000716	Depression	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0002019	Constipation	MP:0020234	decreased basal metabolism	decrease in heat production of an organism at the lowest level of cell chemistry in an inactive, awake, and fasting state
HP:0002902	Hyponatremia	MP:0020215	impaired blood coagulation	impaired ability of the blood to clot
HP:0001402	Hepatocellular carcinoma	MP:0013745	abnormal eyelid margin morphology	any structural anomaly of the confluence of the mucosal surface of the conjunctiva, the edge of the orbicularis, and the cutaneous epithelium
HP:0000016	Urinary retention	MP:0020187	altered susceptibility to prion infection	altered likelihood that an organism will develop ill effects from the small proteinaceous infectious particles which are resistant to inactivation by procedures that modify nucleic acids and which contain an abnormal isoform of a cellular protein that is
HP:0006824	Cranial nerve paralysis	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone

Disease ID	15
Disease	acute intermittent porphyria
Case	(Waiting for update.)