COMP
Basic information
Region (hg38): 19:18782773-18791305
Previous symbols: [ "PSACH", "EDM1", "EPD1" ]
Links
Phenotypes
GenCC
Source:
- pseudoachondroplasia (Definitive), mode of inheritance: AD
- multiple epiphyseal dysplasia type 1 (Limited), mode of inheritance: AD
- pseudoachondroplasia (Supportive), mode of inheritance: AD
- multiple epiphyseal dysplasia type 1 (Supportive), mode of inheritance: AD
- pseudoachondroplasia (Limited), mode of inheritance: Unknown
- multiple epiphyseal dysplasia type 1 (Strong), mode of inheritance: AD
- pseudoachondroplasia (Strong), mode of inheritance: AD
- multiple epiphyseal dysplasia (Definitive), mode of inheritance: AD
- pseudoachondroplasia (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Carpal tunnel syndrome 2; Epiphyseal dysplasia, multiple, 1; Pseudoachondroplasia | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal | 13633894; 3314506; 7907311; 7670471; 7670472; 8725795; 9021009; 9188668; 9887340; 11968079; 14684695; 15266613; 15551305; 17579668; 20301302; 20830670; 21599986; 21644213; 21922596; 21965141; 22006726; 32686688 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (598 variants)
- Pseudoachondroplastic_spondyloepiphyseal_dysplasia_syndrome (113 variants)
- Multiple_epiphyseal_dysplasia_type_1 (104 variants)
- Inborn_genetic_diseases (87 variants)
- not_specified (29 variants)
- COMP-related_disorder (24 variants)
- Multiple_epiphyseal_dysplasia (14 variants)
- Connective_tissue_disorder (12 variants)
- Carpal_tunnel_syndrome_2 (10 variants)
- Epiphyseal_dysplasia,_multiple,_1,_severe (2 variants)
- Pseudoachondroplasia,_severe (1 variants)
- See_cases (1 variants)
- Abnormality_of_the_skeletal_system (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the COMP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000095.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 13 | 104 | 124 | |||
missense | 48 | 102 | 284 | 16 | 453 | |
nonsense | 7 | |||||
start loss | 1 | 1 | ||||
frameshift | 13 | 19 | ||||
splice donor/acceptor (+/-2bp) | 11 | |||||
Total | 52 | 109 | 324 | 120 | 10 |
Highest pathogenic variant AF is 0.0000376443
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
COMP | protein_coding | protein_coding | ENST00000222271 | 19 | 8541 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.35e-9 | 0.997 | 125684 | 0 | 64 | 125748 | 0.000255 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.78 | 348 | 455 | 0.765 | 0.0000270 | 4976 |
Missense in Polyphen | 174 | 242.51 | 0.71749 | 2696 | ||
Synonymous | 0.559 | 178 | 188 | 0.948 | 0.0000123 | 1408 |
Loss of Function | 2.73 | 21 | 39.5 | 0.531 | 0.00000191 | 411 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000639 | 0.000573 |
Ashkenazi Jewish | 0.000695 | 0.000695 |
East Asian | 0.000232 | 0.000217 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000242 | 0.000237 |
Middle Eastern | 0.000232 | 0.000217 |
South Asian | 0.000425 | 0.000425 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin. Can mediate the interaction of chondrocytes with the cartilage extracellular matrix through interaction with cell surface integrin receptors. Could play a role in the pathogenesis of osteoarthritis. Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins (BIRC3, BIRC2, BIRC5 and XIAP). Essential for maintaining a vascular smooth muscle cells (VSMCs) contractile/differentiated phenotype under physiological and pathological stimuli. Maintains this phenotype of VSMCs by interacting with ITGA7 (By similarity). {ECO:0000250, ECO:0000269|PubMed:16051604, ECO:0000269|PubMed:16542502, ECO:0000269|PubMed:17993464}.;
- Disease
- DISEASE: Multiple epiphyseal dysplasia 1 (EDM1) [MIM:132400]: A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. {ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:11565064, ECO:0000269|PubMed:21922596, ECO:0000269|PubMed:7670472, ECO:0000269|PubMed:9021009, ECO:0000269|PubMed:9184241, ECO:0000269|PubMed:9452026, ECO:0000269|PubMed:9463320, ECO:0000269|PubMed:9921895}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pseudoachondroplasia (PSACH) [MIM:177170]: A skeletal dysplasia usually manifesting in the second year of life and characterized by moderate to severe disproportionate short stature, deformity of the lower limbs, brachydactyly, ligamentous laxity, and degenerative joint disease. {ECO:0000269|PubMed:10852928, ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:11746044, ECO:0000269|PubMed:11746045, ECO:0000269|PubMed:21922596, ECO:0000269|PubMed:7670471, ECO:0000269|PubMed:7670472, ECO:0000269|PubMed:9184241, ECO:0000269|PubMed:9452026, ECO:0000269|PubMed:9452063, ECO:0000269|PubMed:9463320, ECO:0000269|PubMed:9921895}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Phagosome - Homo sapiens (human);Malaria - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Integrin cell surface interactions;Extracellular matrix organization;ECM proteoglycans
(Consensus)
Recessive Scores
- pRec
- 0.722
Intolerance Scores
- loftool
- 0.175
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.65
Haploinsufficiency Scores
- pHI
- 0.696
- hipred
- hipred_score
- ghis
- 0.527
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.380
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Comp
- Phenotype
- growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype;
Gene ontology
- Biological process
- skeletal system development;chondrocyte development;apoptotic process;response to unfolded protein;protein secretion;animal organ morphogenesis;multicellular organism aging;animal organ senescence;vascular smooth muscle contraction;protein processing;extracellular matrix organization;collagen fibril organization;bone mineralization;regulation of bone mineralization;BMP signaling pathway;multicellular organism growth;chondrocyte proliferation;tendon development;negative regulation of apoptotic process;skin development;muscle fiber development;artery morphogenesis;musculoskeletal movement;neuromuscular process;limb development;platelet aggregation;vascular smooth muscle cell development;negative regulation of hemostasis;positive regulation of chondrocyte proliferation
- Cellular component
- extracellular region;extracellular space;extracellular matrix;protein-containing complex;collagen-containing extracellular matrix;extracellular exosome
- Molecular function
- protease binding;integrin binding;extracellular matrix structural constituent;calcium ion binding;protein binding;collagen binding;heparin binding;BMP binding;proteoglycan binding;heparan sulfate proteoglycan binding