eRAM
encyclopedia of Rare Disease Annotation for Precision Medicine
| fibrodysplasia ossificans progressiva | ||||
| Disease ID | 140 |
|---|---|
| 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) münchmeyer disease prog myositis ossificans progressive myositis ossificans progressive myositis ossificans (disorder) progressive ossifying myositis |
| Orphanet | |
| OMIM | |
| DOID | |
| UMLS | C0016037 |
| SNOMED-CT | |
| Comorbidity | UMLS | Disease | Sentences' Count(Total Sentences:3) |
| Curated Gene | Entrez_id | Symbol | Resource(Total Genes:3) |
| Inferring Gene | (Waiting for update.) |
| Text Mined Gene | Entrez_id | Symbol | Score | Resource(Total Genes:31) 91 | ACVR1B | 1.97 | DISEASES 94 | ACVRL1 | 1.784 | DISEASES 650 | BMP2 | 2.124 | DISEASES 653 | BMP5 | 2.25 | DISEASES 655 | BMP7 | 2.295 | DISEASES 659 | BMPR2 | 2.081 | DISEASES 2131 | EXT1 | 1.174 | DISEASES 2280 | FKBP1A | 4.522 | DISEASES 642489 | FKBP1C | 4.618 | DISEASES 2316 | FLNA | 1.487 | DISEASES 2591 | GALNT3 | 1.075 | DISEASES 2778 | GNAS | 4.731 | DISEASES 23462 | HEY1 | 2.423 | DISEASES 23493 | HEY2 | 1.701 | DISEASES 3397 | ID1 | 2.595 | DISEASES 3399 | ID3 | 1.608 | DISEASES 2011 | MARK2 | 1.561 | DISEASES 92399 | MRRF | 2.14 | DISEASES 4487 | MSX1 | 1.458 | DISEASES 9241 | NOG | 4.953 | DISEASES 5745 | PTH1R | 1.219 | DISEASES 5916 | RARG | 1.912 | DISEASES 4920 | ROR2 | 2.233 | DISEASES 860 | RUNX2 | 3.068 | DISEASES 6385 | SDC4 | 1.709 | DISEASES 6520 | SLC3A2 | 1.177 | DISEASES 4090 | SMAD5 | 3.73 | DISEASES 4093 | SMAD9 | 3.274 | DISEASES 7010 | TEK | 2.1 | DISEASES 338773 | TMEM119 | 3.291 | DISEASES 51341 | ZBTB7A | 1.911 | DISEASES |
| Locus | Symbol | Locus(Total Locus:1) ACVR1 | 2q24.1 |
| Disease ID | 140 |
|---|---|
| Disease | fibrodysplasia ossificans progressiva |
| Integrated Phenotype | HPO | Name(Total Integrated Phenotypes:20) HP:0010054 | Abnormality of the first metatarsal bone HP:0001250 | Seizures HP:0003306 | Spinal rigidity HP:0001596 | Alopecia HP:0000501 | Glaucoma HP:0001822 | Hallux valgus HP:0002093 | Respiratory insufficiency HP:0010109 | Short hallux HP:0011987 | Ectopic ossification in muscle tissue HP:0000365 | Hearing impairment HP:0001482 | Subcutaneous nodule HP:0003468 | Abnormality of the vertebrae HP:0001508 | Failure to thrive HP:0011989 | Ectopic ossification in ligament tissue HP:0001376 | Limitation of joint mobility HP:0100240 | Synostosis of joints HP:0004209 | Clinodactyly of the 5th finger HP:0001903 | Anemia HP:0010058 | Aplasia/Hypoplasia of the phalanges of the hallux HP:0001249 | Intellectual disability |
| Text Mined Phenotype | HPO | Name | Sentences' Count(Total Phenotypes:6) |
| Disease ID | 140 |
|---|---|
| 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) |
Manually Genotype(Total Manually Genotypes:1) | |||
|---|---|---|---|
| Gene | Mutation | DOI | Article Title |
| ACVR1 | c.617G>A, p.R206H | doi:10.1038/gim.2015.129 | Comprehensive genetic exploration of skeletal dysplasia using targeted exome sequencing |
Text Mining Genotype(Total 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:5) | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chr | Pos | SNP_Id | RefGene | EnsemblGene | ENCODE_Factor | ENCODE_TFBS | Chromosome_interaction | GTEx_eQTL | SNP_TFBS_affinity_GWAS3D | SNP_miRNA_target_affinity_PolymiRTS | SNP_splicing_effect_Skippy | SNP_splicing_effect_MutPred_Splice | SNP_ns_protein_effect_dbNSFP | SNP_syn_effect_Silva | SNP_phosphorylation_effect_PhosSNP | PhastCons_score | PhyloP_score | GERP++_RS | Segway_state | Ancestral_allele | ESP_AF | ESP_AFR | ESP_AFR | ESP_EUR | TG_ASN | TG_AMR | TG_AFR | TG_EUR | Type | Consequence | bStatistic | EncH3K27Ac | EncH3K4Me1 | EncH3K4Me3 | EncNucleo | OMIM | Clinvar |
| 6 | 167418111 | rs56101842 | NM_007045,FGFR1OP | NM_194429,FGFR1OP | ENST00000366847,ENSG00000213066 | ENST00000283506,ENSG00000213066 | ENST00000420493,ENSG00000213066 | ENST00000349556,ENSG00000213066 | ENST00000494781,ENSG00000213066 | ENST00000476078,ENSG00000213066 | MCV-1 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 0.014 | 1.262 | 1.19 | GM0 | A | NA | NA | NA | NA | NA | NA | NA | NA | Transcript | INTRONIC | 940 |
| 6 | 167431147 | rs12526548 | NM_007045,FGFR1OP | NM_194429,FGFR1OP | ENST00000366847,ENSG00000213066 | ENST00000283506,ENSG00000213066 | ENST00000420493,ENSG00000213066 | ENST00000349556,ENSG00000213066 | NA | NA | NA | NA | LM31,3.6393 | LM59,1.6173 | LM83,7.5429 | LM132,2.3701 | LM182,2.6754 | NA | NA | NA | NA | NA | NA | 0.036 | 0.530 | 1.6 | F0 | T | NA | NA | NA | NA | NA | NA | NA | NA | Transcript |
| 6 | 167435325 | rs7749278 | NM_007045,FGFR1OP | NM_194429,FGFR1OP | ENST00000366847,ENSG00000213066 | ENST00000283506,ENSG00000213066 | ENST00000420493,ENSG00000213066 | ENST00000349556,ENSG00000213066 | ENST00000496181,ENSG00000213066 | NA | NA | NA | NA | LM130,2.6584 | LM173,2.4177 | Bapx1,2.1691 | CCAAT-box,1.3678 | Tst-1,1.4843 | NA | NA | NA | NA | NA | NA | 0.000 | -4.464 | -5.37 | GE1 | C | NA | NA | NA | NA | NA | NA | NA | NA |
| 6 | 167437988 | rs2301436 | NM_007045,FGFR1OP | NM_194429,FGFR1OP | ENST00000366847,ENSG00000213066 | ENST00000283506,ENSG00000213066 | ENST00000420493,ENSG00000213066 | ENST00000349556,ENSG00000213066 | ENST00000496181,ENSG00000213066 | ENST00000488525,ENSG00000213066 | MCV-3 | NA | NA | NA | LM81,1.3675 | LM158,1.7146 | LM173,2.3154 | LM185,27.2586 | LM201,26.9577 | NA | NA | NA | NA | NA | NA | 0.233 | 0.430 | 1.3 | GE1 | T | NA | NA | NA | NA | NA | NA | NA |
| 6 | 167445139 | rs2282859 | NM_007045,FGFR1OP | NM_194429,FGFR1OP | ENST00000366847,ENSG00000213066 | ENST00000283506,ENSG00000213066 | ENST00000420493,ENSG00000213066 | ENST00000349556,ENSG00000213066 | ENST00000488525,ENSG00000213066 | TFP.GATA2 | TFP.EP300 | TFP.RAD21 | MCV-6 | NA | chr6,167440001,167450000,chr19,2570001,2580000,8,Hi-C | NA | Asg1-DBD-primary,1.3131 | Mbp1-primary,1.8714 | Mbp1-primary,1.3045 | Pknox1_2364,1.4384 | Pknox1_2364,1.9592 | NA | NA | NA | NA | NA | NA | 0.001 | -0.326 | -1.12 | GM0 | T | NA | NA | NA | NA | NA |
GWASdb Snp Trait(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
Mapped by lexical matching(Total Items:9) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0011989 | Ectopic ossification in ligament tissue | MP:0003988 | disorganized embryonic tissue | a lack of the regular arrangement of any embryonic tissues |
| HP:0001376 | Limitation of joint mobility | MP:0010732 | abnormal node of Ranvier morphology | any structural anomaly of the short unmyelinated segments of an axon between myelinated segments, where voltage gated channels accumulate and regenerate an action potential as it is conducted along the axon |
| HP:0100240 | Synostosis of joints | MP:0004686 | decreased length of long bones | reduced end-to-end length of the several elongated bones of the extremities |
| HP:0011987 | Ectopic ossification in muscle tissue | MP:0009415 | skeletal muscle degeneration | pathological deterioration of skeletal muscle tissue, often accompanied by loss of function |
| HP:0003468 | Abnormality of the vertebrae | MP:0009657 | failure of chorioallantoic fusion | failure to initiate and/or complete the formation of a highly vascularized extra-embryonic fetal membrane by fusion of the chorion and allantois |
| HP:0004209 | Clinodactyly of the 5th finger | MP:0011665 | d-loop transposition of the great arteries | complete transposition of the great arteries; the d- refers to the dextroposition of the bulboventricular loop (ie, the position of the right ventricle, which is on the right side); in addition, the aorta also tends to be on the right and anterior, and th |
| HP:0001508 | Failure to thrive | MP:0013294 | prenatal lethality prior to heart atrial septation | death prior to the completion of heart atrial septation (Mus: E14.5-15.5) |
| HP:0010054 | Abnormality of the first metatarsal bone | MP:0014167 | ectopic bone | the appearance of an extra bone structure at an atypical location |
| HP:0010109 | Short hallux | MP:0009001 | absent hallux | absence of the first or primary digit of the foot |
Mapped by homologous gene(Total Items:19) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0011987 | Ectopic ossification in muscle tissue | MP:0014167 | ectopic bone | the appearance of an extra bone structure at an atypical location |
| HP:0011989 | Ectopic ossification in ligament tissue | MP:0014167 | ectopic bone | the appearance of an extra bone structure at an atypical location |
| HP:0002093 | Respiratory insufficiency | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0001822 | Hallux valgus | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0004209 | Clinodactyly of the 5th finger | MP:0020157 | abnormal behavioral response to alcohol | any anomaly in the behavioral response induced by alcohol, such as induced hyperactivity or stereotypic behavior |
| HP:0100240 | Synostosis of joints | MP:0014178 | increased brain apoptosis | increase in the number of cells of the brain undergoing programmed cell death |
| HP:0001508 | Failure to thrive | 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:0003306 | Spinal rigidity | 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:0001249 | Intellectual disability | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| 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:0003468 | Abnormality of the vertebrae | MP:0014198 | absent pituitary infundibular stalk | absence of the apical portion of the tubular structure extending from the hypothalamus to the posterior lobe of the pituitary gland |
| HP:0000365 | Hearing impairment | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0010054 | Abnormality of the first metatarsal bone | MP:0014167 | ectopic bone | the appearance of an extra bone structure at an atypical location |
| HP:0001482 | Subcutaneous nodule | MP:0013542 | abnormal submandibular gland branching morphogenesis | |
| HP:0001376 | Limitation of joint mobility | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0010109 | Short hallux | MP:0020040 | decreased bone ossification | decrease in the formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance |
| HP:0000501 | Glaucoma | 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:0001903 | Anemia | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| HP:0001596 | Alopecia | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| Disease ID | 140 |
|---|---|
| Disease | fibrodysplasia ossificans progressiva |
| Case | (Waiting for update.) |