COMP

cartilage oligomeric matrix protein, the group of Thrombospondin family

Basic information

Region (hg38): 19:18782773-18791305

Previous symbols: [ "PSACH", "EDM1", "EPD1" ]

Links

ENSG00000105664NCBI:1311OMIM:600310HGNC:2227Uniprot:P49747AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Carpal tunnel syndrome 2; Epiphyseal dysplasia, multiple, 1; PseudoachondroplasiaADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal13633894; 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 ClinVar and linked to the COMP gene.

  • 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.

EffectPLPVUSLBBSum
synonymous
13
clinvar
104
clinvar
7
clinvar
124
missense
48
clinvar
102
clinvar
284
clinvar
16
clinvar
3
clinvar
453
nonsense
7
clinvar
7
start loss
1
1
frameshift
3
clinvar
3
clinvar
13
clinvar
19
splice donor/acceptor (+/-2bp)
1
clinvar
4
clinvar
6
clinvar
11
Total 52 109 324 120 10

Highest pathogenic variant AF is 0.0000376443

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
COMPprotein_codingprotein_codingENST00000222271 198541
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.35e-90.9971256840641257480.000255
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.783484550.7650.00002704976
Missense in Polyphen174242.510.717492696
Synonymous0.5591781880.9480.00001231408
Loss of Function2.732139.50.5310.00000191411

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006390.000573
Ashkenazi Jewish0.0006950.000695
East Asian0.0002320.000217
Finnish0.000.00
European (Non-Finnish)0.0002420.000237
Middle Eastern0.0002320.000217
South Asian0.0004250.000425
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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