PedAM

Pediatric Disease Annotations & Medicines


	fibrodysplasia ossificans progressiva

Disease ID	195
Disease	fibrodysplasia ossificans progressiva
Definition	disease characterized by bony deposits or the ossification of muscle tissue.
Synonym	diffuse progressive ossifying polymyositis fibrodysplasia ossificans congenita fop fop - fibrodysplasia ossificans progressiva muenchmeyer syndrome myositis ossificans progressiva myositis ossificans progressiva (disorder) mÃ¼nchmeyer disease prog myositis ossificans progressive myositis ossificans progressive myositis ossificans (disorder) progressive ossifying myositis
Orphanet	ORPHANET:337
OMIM	OMIM:135100 OMIM:614206
DOID	DOID:13374
UMLS	C0016037
SNOMED-CT	SNOMEDCT_US_2016_09_01:82725007
Comorbidity	UMLS \| Disease \| Sentences' Count(Total Sentences:2) C1145670 \| respiratory failure \| 1 C0029423 \| osteochondromas \| 1
Curated Gene	Entrez_id \| Symbol \| Resource(Total Genes:3) GNAS \| 2778 \| GHR CHTOP \| 26097 \| OMIM ACVR1 \| 90 \| CLINVAR;UNIPROT;ORPHANET;GHR
Inferring Gene	(Waiting for update.)
Text Mined Gene	Entrez_id \| Symbol \| Score \| Resource(Total Genes:66) 8646 \| CHRD \| DISEASES 3956 \| LGALS1 \| DISEASES 657 \| BMPR1A \| DISEASES 2026 \| ENO2 \| DISEASES 4488 \| MSX2 \| DISEASES 92 \| ACVR2A \| DISEASES 1959 \| EGR2 \| DISEASES 130399 \| ACVR1C \| DISEASES 652 \| BMP4 \| DISEASES 2658 \| GDF2 \| DISEASES 4654 \| MYOD1 \| DISEASES 10468 \| FST \| DISEASES 4092 \| SMAD7 \| DISEASES 9135 \| RABEP1 \| DISEASES 2769 \| GNA15 \| DISEASES 443 \| ASPA \| DISEASES 90 \| ACVR1 \| DISEASES 2817 \| GPC1 \| DISEASES 658 \| BMPR1B \| DISEASES 9759 \| HDAC4 \| DISEASES 2588 \| GALNS \| DISEASES 3145 \| HMBS \| DISEASES 4319 \| MMP10 \| DISEASES 1834 \| DSPP \| DISEASES 654 \| BMP6 \| DISEASES 56172 \| ANKH \| DISEASES 4091 \| SMAD6 \| DISEASES 3549 \| IHH \| DISEASES 6469 \| SHH \| DISEASES 26585 \| GREM1 \| DISEASES 121340 \| SP7 \| DISEASES 649 \| BMP1 \| DISEASES 2353 \| FOS \| DISEASES 493829 \| TRIM72 \| DISEASES 28959 \| TMEM176B \| DISEASES 5745 \| PTH1R \| DISEASES 51341 \| ZBTB7A \| DISEASES 9241 \| NOG \| DISEASES 23462 \| HEY1 \| DISEASES 92399 \| MRRF \| DISEASES 23493 \| HEY2 \| DISEASES 2316 \| FLNA \| DISEASES 642489 \| FKBP1C \| DISEASES 653 \| BMP5 \| DISEASES 2778 \| GNAS \| DISEASES 860 \| RUNX2 \| DISEASES 6385 \| SDC4 \| DISEASES 3399 \| ID3 \| DISEASES 659 \| BMPR2 \| DISEASES 4920 \| ROR2 \| DISEASES 3397 \| ID1 \| DISEASES 6520 \| SLC3A2 \| DISEASES 2131 \| EXT1 \| DISEASES 650 \| BMP2 \| DISEASES 4093 \| SMAD9 \| DISEASES 7010 \| TEK \| DISEASES 2280 \| FKBP1A \| DISEASES 4487 \| MSX1 \| DISEASES 94 \| ACVRL1 \| DISEASES 2591 \| GALNT3 \| DISEASES 338773 \| TMEM119 \| DISEASES 5916 \| RARG \| DISEASES 655 \| BMP7 \| DISEASES 2011 \| MARK2 \| DISEASES 4090 \| SMAD5 \| DISEASES 91 \| ACVR1B \| DISEASES
Locus	Symbol \| Locus(Total Locus:1) ACVR1 \| 2q24.1

Disease ID	195
Disease	fibrodysplasia ossificans progressiva
Integrated Phenotype	HPO \| Name(Total Integrated Phenotypes:20) HP:0001903 \| Anemia HP:0001596 \| Alopecia HP:0100240 \| Synostosis of joints HP:0010109 \| Short hallux HP:0010058 \| Aplasia/Hypoplasia of the phalanges of the hallux HP:0001376 \| Limitation of joint mobility HP:0001249 \| Intellectual disability HP:0000501 \| Glaucoma HP:0003306 \| Spinal rigidity HP:0001250 \| Seizures HP:0001508 \| Failure to thrive HP:0011987 \| Ectopic ossification in muscle tissue HP:0001482 \| Subcutaneous nodule HP:0002093 \| Respiratory insufficiency HP:0004209 \| Clinodactyly of the 5th finger HP:0011989 \| Ectopic ossification in ligament tissue HP:0000365 \| Hearing impairment HP:0003468 \| Abnormality of the vertebrae HP:0001822 \| Hallux valgus HP:0010054 \| Abnormality of the first metatarsal bone
Text Mined Phenotype	HPO \| Name \| Sentences' Count(Total Phenotypes:6) HP:0011986 \| Ectopic bone formation \| 2 HP:0002878 \| Respiratory failure \| 1 HP:0000347 \| Hypoplasia of mandible \| 1 HP:0010531 \| Spinal myoclonus \| 1 HP:0001336 \| Myoclonic jerks \| 1 HP:0030431 \| Osteochondromas \| 1

Disease ID	195
Disease	fibrodysplasia ossificans progressiva
Manually Symptom	UMLS \| Name(Total Manually Symptoms:12) C1704356 \| enchondroma C1642403 \| corneal keloid C1444565 \| cardiorespiratory failure C1281300 \| vascular degeneration C0749108 \| submandibular swelling C0700208 \| scoliosis C0206641 \| multiple osteochondromas C0158369 \| limb swelling C0029423 \| osteochondromas C0027122 \| myositis ossificans C0007114 \| skin cancers C0003090 \| ankylosis
Text Mined Symptom	UMLS \| Name \| Sentences' Count(Total Symptoms:2) C1444565 \| cardiorespiratory failure \| 1 C0029423 \| osteochondromas \| 1

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

All Snps(Total Genotypes:29)
snpId	pubmedId	geneId	geneSymbol	diseaseId	sourceId	sentence	score	Year	geneSymbol_dbSNP	CHROMOSOME	POS	REF	ALT
rs121912678	22508565	90	ACVR1	umls:C0016037	BeFree	An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva.	0.45302921	2012	ACVR1	2	157774114	C	T,G
rs121912678	22174087	90	ACVR1	umls:C0016037	BeFree	Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva.	0.45302921	2012	ACVR1	2	157774114	C	T,G
rs121912678	17351709	83729	INHBE	umls:C0016037	BeFree	The 617G>A (R206H) mutation in the activin receptor type IA (ACVR1) gene has been identified in all examined individuals with FOP of various ethnic groups, including Caucasian and Chinese descents.	0.001357209	2007	ACVR1	2	157774114	C	T,G
rs121912678	21460849	90	ACVR1	umls:C0016037	BeFree	In addition, an RAR-γ agonist blocked heterotopic ossification in transgenic mice expressing activin receptor-like kinase-2 (ALK2) Q207D, a constitutively active form of the receptor that is related to ALK2 R206H found in individuals with fibrodysplasia ossificans progressiva.	0.45302921	2011	ACVR1	2	157774114	C	T,G
rs121912678	19929436	4086	SMAD1	umls:C0016037	BeFree	Expression of the mutant ALK2-R206H receptor (FOP-ALK2) results in increased phosphorylation of the downstream Smad1 effector proteins and elevated basal BMP-dependent transcriptional reporter activity, indicating that FOP-ALK2 is constitutively active.	0.000542884	2010	ACVR1	2	157774114	C	T,G
rs121912678	21377447	90	ACVR1	umls:C0016037	BeFree	The activities of ALK2(L196P) were higher than those of ALK2(G356D), another mutant ALK2 allele found in patients with FOP and were equivalent to those of ALK2(R206H), a typical mutation found in patients with FOP.	0.45302921	2011	ACVR1	2	157774114	C	T,G
rs121912678	22408652	90	ACVR1	umls:C0016037	BeFree	Nearly all cases of FOP are caused by the identical mutation in the ACVR1 gene that causes a single amino acid substitution, R206H, in the bone morphogenetic protein (BMP) type I receptor ACVR1 (formerly known as ALK2).	0.45302921	2014	ACVR1	2	157774114	C	T,G
rs121912678	18203193	90	ACVR1	umls:C0016037	BeFree	A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H).	0.45302921	2008	ACVR1	2	157774114	C	T,G
rs121912678	20577760	90	ACVR1	umls:C0016037	BeFree	Genetic analysis confirmed the presence of the classic FOP mutation (ACVR1 c.617G>A; R206H).	0.45302921	2010	ACVR1	2	157774114	C	T,G
rs121912678	19929436	2617	GARS	umls:C0016037	BeFree	Expression of the mutant ALK2-R206H receptor (FOP-ALK2) results in increased phosphorylation of the downstream Smad1 effector proteins and elevated basal BMP-dependent transcriptional reporter activity, indicating that FOP-ALK2 is constitutively active.	0.000542884	2010	ACVR1	2	157774114	C	T,G
rs121912678	22133093	90	ACVR1	umls:C0016037	BeFree	Classic FOP is caused by a recurrent activating mutation (617G>A; R206H) in the gene ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor.	0.45302921	2011	ACVR1	2	157774114	C	T,G
rs121912678	19929436	90	ACVR1	umls:C0016037	BeFree	ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation.	0.45302921	2010	ACVR1	2	157774114	C	T,G
rs121912678	18684712	4092	SMAD7	umls:C0016037	BeFree	Gene transfer of Smad7 or inhibition of type I receptors with dorsomorphin may represent strategies for blocking the activity induced by ALK2(R206H) in FOP.	0.000271442	2009	ACVR1	2	157774114	C	T,G
rs121912678	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157774114	C	T,G
rs121912678	24798338	90	ACVR1	umls:C0016037	BeFree	Fibrodysplasia ossificans progressiva is characterized by extensive ossification within muscle tissues, and its molecular pathogenesis is responsible for the constitutively activating mutation (R206H) of the bone morphogenetic protein type 1 receptor, activin-like kinase 2 (ALK2).	0.45302921	2014	ACVR1	2	157774114	C	T,G
rs121912678	22130450	90	ACVR1	umls:C0016037	BeFree	Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva.	0.45302921	2012	ACVR1	2	157774114	C	T,G
rs121912678	22174087	2651	GCNT2	umls:C0016037	BeFree	Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva.	0.000271442	2012	ACVR1	2	157774114	C	T,G
rs121912679	18952055	90	ACVR1	umls:C0016037	BeFree	A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor.	0.45302921	2008	ACVR1	2	157761077	C	T
rs121912679	18203193	90	ACVR1	umls:C0016037	BeFree	A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H).	0.45302921	2008	ACVR1	2	157761077	C	T
rs121912679	22130450	90	ACVR1	umls:C0016037	BeFree	Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva.	0.45302921	2012	ACVR1	2	157761077	C	T
rs121912679	21377447	90	ACVR1	umls:C0016037	BeFree	The activities of ALK2(L196P) were higher than those of ALK2(G356D), another mutant ALK2 allele found in patients with FOP and were equivalent to those of ALK2(R206H), a typical mutation found in patients with FOP.	0.45302921	2011	ACVR1	2	157761077	C	T
rs121912679	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157761077	C	T
rs121912680	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157770384	C	T,G
rs199566527	22529972	9241	NOG	umls:C0016037	BeFree	We conclude that p.G92E represents a rare polymorphism of the NOGGIN gene-- causing neither brachydactyly nor fibrodysplasia ossificans progressiva.	0.002171535	2012	NOG	17	56594498	G	A
rs387906588	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157766005	C	A
rs387906589	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157766004	C	T
rs387906590	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157761020	C	G
rs387906591	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157774126	C	A
rs797045135	NA	90	ACVR1	umls:C0016037	CLINVAR	NA	0.45302921	NA	ACVR1	2	157774144	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)
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Mapped by homologous gene(Total Items:0)
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Chemical(Total Drugs:0)
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FDA approved drug and dosage information(Total Drugs:0)
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FDA labeling changes(Total Drugs:0)
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