COMP

cartilage oligomeric matrix protein, the group of Thrombospondin family

Basic information

Region (hg38): 19:18782772-18791305

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

Links

ENSG00000105664 ∙ NCBI:1311 ∙ OMIM:600310 ∙ HGNC:2227 ∙ Uniprot:P49747 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pseudoachondroplasia (Definitive), mode of inheritance: AD
• 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

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 ClinVar and linked to the COMP gene.

• not provided (423 variants)
• Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome (100 variants)
• Multiple epiphyseal dysplasia type 1 (93 variants)
• not specified (26 variants)
• Inborn genetic diseases (26 variants)
• Multiple epiphyseal dysplasia (14 variants)
• Connective tissue disorder (13 variants)
• COMP-related disorders (3 variants)
• Carpal tunnel syndrome 2 (2 variants)
• COMP-related condition (2 variants)
• Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome;Multiple epiphyseal dysplasia type 1 (1 variants)
• Multiple epiphyseal dysplasia type 1;Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome (1 variants)
• Multiple epiphyseal dysplasia type 1;Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome;Carpal tunnel syndrome 2 (1 variants)
• Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome;Carpal tunnel syndrome 2;Multiple epiphyseal dysplasia type 1 (1 variants)
• Carpal tunnel syndrome 2;Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome;Multiple epiphyseal dysplasia type 1 (1 variants)
• Abnormality of the skeletal system (1 variants)
• See cases (1 variants)
• Pseudoachondroplasia, severe (1 variants)
• Carpal tunnel syndrome 2;Multiple epiphyseal dysplasia type 1;Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			11	60	8	79
missense	38	77	153	8	3	279
nonsense			7			7
start loss			1			1
frameshift		2	8			10
inframe indel	2	9	4			15
splice donor/acceptor (+/-2bp)		3	4			7
splice region			10	10	1	21
non coding			11	37	29	77
Total	40	91	199	105	40

Highest pathogenic variant AF is 0.00000658

Variants in COMP

This is a list of pathogenic ClinVar variants found in the COMP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-18782804-T-C		Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome • Multiple epiphyseal dysplasia type 1	Uncertain significance (Jan 12, 2018)
19-18782823-C-T		Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome • Multiple epiphyseal dysplasia type 1	Benign/Likely benign (Nov 10, 2018)
19-18782854-C-T			Benign (Mar 03, 2015)
19-18782900-T-C		Multiple epiphyseal dysplasia type 1 • Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome	Benign (Jan 12, 2018)
19-18782914-C-G		not specified • Multiple epiphyseal dysplasia type 1 • Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome	Benign (Aug 20, 2018)
19-18782917-A-G		COMP-related disorder	Uncertain significance (Apr 28, 2017)
19-18782922-T-C		not specified • Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome • Multiple epiphyseal dysplasia type 1	Benign (Jan 25, 2024)
19-18782925-C-T			Uncertain significance (Jul 28, 2023)
19-18782926-G-A			Likely benign (Sep 01, 2023)
19-18782927-C-T		not specified	Benign/Likely benign (Nov 01, 2023)
19-18782944-A-G			Uncertain significance (Jun 13, 2022)
19-18782947-C-T			Uncertain significance (Oct 05, 2022)
19-18782957-G-T			Likely benign (May 31, 2022)
19-18782959-T-A			Uncertain significance (Oct 29, 2022)
19-18782964-G-A			Uncertain significance (Feb 29, 2020)
19-18782973-G-A			Likely benign (Oct 30, 2022)
19-18782980-C-T			Benign (Dec 13, 2023)
19-18782981-G-A			Likely benign (Feb 10, 2022)
19-18783001-A-G		not specified	Benign (Mar 03, 2015)
19-18783036-C-T			Benign (Jul 07, 2023)
19-18783041-G-A			Uncertain significance (Feb 08, 2022)
19-18783046-C-T		Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome • Multiple epiphyseal dysplasia type 1 • Connective tissue disorder	Benign/Likely benign (Jan 24, 2024)
19-18783047-G-A			Likely benign (Mar 15, 2023)
19-18783055-A-G			Uncertain significance (Feb 21, 2017)
19-18783057-T-TG		Multiple epiphyseal dysplasia type 1	Pathogenic (Jan 01, 2003)

GnomAD

Source: gnomAD

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: 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
• 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