COMP

Summary

COMP (cartilage oligomeric matrix protein, HGNC:2227) is a protein-coding gene on chromosome 19p13.11, encoding Cartilage oligomeric matrix protein (P49747). Plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin.

The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Contraction or expansion of a 5 aa aspartate repeat and other mutations can cause pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED).

Source: NCBI Gene 1311 — RefSeq curated summary.

At a glance

• Gene–disease (curated): COMP-related skeletal dysplasia (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 927 total — 54 pathogenic, 88 likely-pathogenic (top 3% of genes corpus-wide)
• GTEx eGene: eQTL in 14 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 93
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.07 (unconstrained)
• MANE Select transcript: NM_000095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2227
Approved symbol	COMP
Name	cartilage oligomeric matrix protein
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	MED, THBS5, TSP5, TSP-5
Ensembl gene	ENSG00000105664
Ensembl biotype	protein_coding
OMIM	600310
Entrez	1311

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000222271

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2

ENST00000222271, ENST00000425807, ENST00000542601, ENST00000612179, ENST00000944187, ENST00000944188, ENST00001037220, ENST00001123668

RefSeq mRNA: 1 — MANE Select: NM_000095 NM_000095

CCDS: CCDS12385

Canonical transcript exons

ENST00000222271 — 19 exons

Exon	Start	End
ENSE00000690352	18790562	18790613
ENSE00000690354	18790850	18790935
ENSE00002410667	18791191	18791305
ENSE00002990811	18789160	18789297
ENSE00002994550	18786532	18786650
ENSE00003077336	18788592	18788750
ENSE00003091449	18788839	18788913
ENSE00003103541	18789942	18790114
ENSE00003111278	18787491	18787650
ENSE00003116721	18788212	18788319
ENSE00003128675	18788410	18788514
ENSE00003143164	18782773	18782961
ENSE00003143260	18785498	18785546
ENSE00003146191	18785673	18785851
ENSE00003159325	18784191	18784363
ENSE00003190692	18783054	18783193
ENSE00003192317	18785965	18786146
ENSE00003218232	18784896	18785092
ENSE00003631787	18786239	18786291

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 99.87.

FANTOM5 (CAGE): breadth broad, TPM avg 50.3105 / max 11530.3989, expressed in 293 samples.

Highest expression (Bgee): tibia, cartilage tissue, calcaneal tendon, tendon of biceps brachii, synovial joint.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COMP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	1.5e-12	+0.72	19:18734866:C:G
Brain Cerebellum	eqtl	4.2e-12	+0.74	19:18770213:T:C
Thyroid	eqtl	1.4e-04	-0.24	19:18794384:C:T
Skin Sun Exposed Lower leg	eqtl	4.2e-04	+0.16	19:18801332:CA:C
Artery Tibial	eqtl	4.3e-04	+0.24	19:18800572:C:T
Lung	eqtl	4.9e-04	-0.26	19:18794384:C:T
Pancreas	eqtl	1.6e-03	-0.29	19:18795844:G:T
Testis	sqtl	2.5e-03	+0.46	19:18762107:A:G
Breast Mammary Tissue	eqtl	1.2e-02	-0.19	19:18795844:G:T
Adipose Visceral Omentum	eqtl	2.0e-02	-0.77	19:18715747:G:T
Colon Sigmoid	eqtl	2.6e-02	+0.44	19:18758177:C:T
Brain Caudate basal ganglia	eqtl	3.8e-02	-0.32	19:19461299:T:G
Nerve Tibial	eqtl	4.0e-02	+0.53	19:18463444:C:T
Adipose Subcutaneous	eqtl	4.1e-02	+0.15	19:18801332:CA:C
Stomach	eqtl	4.4e-02	-1.01	19:19766467:T:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
180094	49.7492	293
180067	0.2615	56
180066	0.1428	41
180064	0.0977	31
180065	0.0403	20
180093	0.0190	8

Top tissues by expression

showing 100 of 280 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.87	gold quality
cartilage tissue	UBERON:0002418	99.65	gold quality
calcaneal tendon	UBERON:0003701	99.59	gold quality
tendon of biceps brachii	UBERON:0008188	99.46	gold quality
synovial joint	UBERON:0002217	99.08	gold quality
tendon	UBERON:0000043	98.44	gold quality
popliteal artery	UBERON:0002250	98.37	gold quality
tibial artery	UBERON:0007610	98.36	gold quality
saphenous vein	UBERON:0007318	98.22	gold quality
aorta	UBERON:0000947	95.87	gold quality
urethra	UBERON:0000057	94.74	gold quality
ascending aorta	UBERON:0001496	92.97	gold quality
skin of leg	UBERON:0001511	92.93	gold quality
thoracic aorta	UBERON:0001515	92.91	gold quality
descending thoracic aorta	UBERON:0002345	92.29	gold quality
layer of synovial tissue	UBERON:0007616	92.16	gold quality
pericardium	UBERON:0002407	90.34	gold quality
left coronary artery	UBERON:0001626	89.76	gold quality
right coronary artery	UBERON:0001625	89.74	gold quality
trabecular bone tissue	UBERON:0002483	89.24	gold quality
coronary artery	UBERON:0001621	88.73	gold quality
tibial nerve	UBERON:0001323	87.95	gold quality
zone of skin	UBERON:0000014	87.08	gold quality
skin of abdomen	UBERON:0001416	85.76	gold quality
right atrium auricular region	UBERON:0006631	83.77	gold quality
gall bladder	UBERON:0002110	83.54	gold quality
hair follicle	UBERON:0002073	83.10	gold quality
periodontal ligament	UBERON:0008266	82.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	81.67	gold quality
cardiac atrium	UBERON:0002081	81.43	gold quality
blood vessel layer	UBERON:0004797	81.28	gold quality
right testis	UBERON:0004534	80.82	gold quality
minor salivary gland	UBERON:0001830	79.69	gold quality
left testis	UBERON:0004533	79.59	gold quality
mouth mucosa	UBERON:0003729	78.80	gold quality
amniotic fluid	UBERON:0000173	77.91	gold quality
penis	UBERON:0000989	77.87	gold quality
visceral pleura	UBERON:0002401	77.86	gold quality
testis	UBERON:0000473	77.80	gold quality
seminal vesicle	UBERON:0000998	77.19	gold quality
vagina	UBERON:0000996	77.11	gold quality
triceps brachii	UBERON:0001509	76.11	gold quality
gingiva	UBERON:0001828	75.74	gold quality
tongue squamous epithelium	UBERON:0006919	75.69	gold quality
lower esophagus mucosa	UBERON:0035834	75.56	gold quality
omental fat pad	UBERON:0010414	75.42	gold quality
peritoneum	UBERON:0002358	75.37	gold quality
paraflocculus	UBERON:0005351	75.36	gold quality
saliva-secreting gland	UBERON:0001044	75.13	gold quality
right lobe of thyroid gland	UBERON:0001119	75.03	gold quality
connective tissue	UBERON:0002384	74.92	gold quality
frontal pole	UBERON:0002795	74.84	gold quality
middle frontal gyrus	UBERON:0002702	74.56	gold quality
esophagus mucosa	UBERON:0002469	74.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	74.25	gold quality
adipose tissue	UBERON:0001013	73.91	gold quality
right lung	UBERON:0002167	73.67	gold quality
trachea	UBERON:0003126	73.67	gold quality
ectocervix	UBERON:0012249	73.40	gold quality
corpus epididymis	UBERON:0004359	72.73	gold quality
caput epididymis	UBERON:0004358	72.05	gold quality
mammalian vulva	UBERON:0000997	71.87	gold quality
gingival epithelium	UBERON:0001949	71.62	silver quality
vena cava	UBERON:0004087	71.56	silver quality
smooth muscle tissue	UBERON:0001135	71.45	gold quality
upper lobe of left lung	UBERON:0008952	70.84	gold quality
heart	UBERON:0000948	70.71	gold quality
nipple	UBERON:0002030	70.51	gold quality
upper arm skin	UBERON:0004263	70.42	silver quality
gastrocnemius	UBERON:0001388	70.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.04	gold quality
skin of hip	UBERON:0001554	69.78	gold quality
tibialis anterior	UBERON:0001385	69.74	silver quality
upper lobe of lung	UBERON:0008948	69.73	gold quality
cerebellar hemisphere	UBERON:0002245	69.64	gold quality
cerebellar cortex	UBERON:0002129	69.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	69.03	gold quality
left lobe of thyroid gland	UBERON:0001120	68.88	gold quality
gluteal muscle	UBERON:0002000	68.75	gold quality
prostate gland	UBERON:0002367	68.13	gold quality
cerebellum	UBERON:0002037	67.80	gold quality
thyroid gland	UBERON:0002046	67.48	gold quality
muscle of leg	UBERON:0001383	67.15	gold quality
apex of heart	UBERON:0002098	66.54	gold quality
esophagus	UBERON:0001043	66.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	66.36	gold quality
body of tongue	UBERON:0011876	65.81	gold quality
superficial temporal artery	UBERON:0001614	65.69	gold quality
muscle organ	UBERON:0001630	65.26	gold quality
endometrium epithelium	UBERON:0004811	64.90	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.67	gold quality
bone element	UBERON:0001474	64.49	gold quality
tongue	UBERON:0001723	64.30	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	64.27	gold quality
placenta	UBERON:0001987	64.24	gold quality
stromal cell of endometrium	CL:0002255	64.13	gold quality
myometrium	UBERON:0001296	64.01	gold quality
heart left ventricle	UBERON:0002084	63.64	gold quality
cardiac ventricle	UBERON:0002082	63.28	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 63 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Vagina	tissue	22.1
Gallbladder	tissue	15.1
Smooth muscle	tissue	11.3
Heart muscle	tissue	8.2
Placenta	tissue	7.7
Epididymis	tissue	7.2
Seminal vesicle	tissue	6.3
Urinary bladder	tissue	6.1
Adipose tissue	tissue	5.8
Testis	tissue	5.7
Prostate	tissue	3.9
Skin 1	tissue	3.5
Lymph node	tissue	3.4
Esophagus	tissue	2.5
Parathyroid gland	tissue	2.1
Endometrium 1	tissue	1.8
Lung	tissue	1.7
Salivary gland	tissue	1.6
Cerebellum	tissue	1.1
Appendix	tissue	1.1
Cervix	tissue	1.0
Breast	tissue	0.9
Olfactory bulb	tissue	0.9
Superior colliculi	tissue	0.7
Pancreas	tissue	0.6
Tongue	tissue	0.5
Spinal cord	tissue	0.5
Hippocampal formation	tissue	0.5
Entorhinal cortex	tissue	0.5
Pituitary gland	tissue	0.3
Cerebral cortex	tissue	0.3
Substantia nigra	tissue	0.3
Thyroid gland	tissue	0.3
Tonsil	tissue	0.3
Somatosensory cortex	tissue	0.3
Temporal cortex	tissue	0.3
Prefrontal cortex	tissue	0.2
Skeletal muscle	tissue	0.2
Colon	tissue	0.2
Motor cortex	tissue	0.2
Frontal cortex	tissue	0.2
Medulla oblongata	tissue	0.2
Kidney	tissue	0.2
Adrenal gland	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Retrosplenial cortex	tissue	0.2
Occipital cortex	tissue	0.2
Insular cortex	tissue	0.2
Stomach 1	tissue	0.1
Basal ganglia	tissue	0.1
Amygdala	tissue	0.1
Choroid plexus	tissue	0.1
Midbrain	tissue	0.1
Thalamus	tissue	0.1
Hypothalamus	tissue	0.1
Liver	tissue	0.1
Locus coeruleus	tissue	0.1
Thymus	tissue	0.1
Ventral forebrain	tissue	0.1
Periaqueductal gray	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 66; highest nTPM — Blood vessel (333.9), Flocculonodular lobe (2.8), Vermis (1.9), Cerebellar cortex (1.7), Cervical spinal cord, ventral horn (0.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREBRF, GLI3, SON, SOX17, SOX5, SOX6, SOX9, SP1, TBXT, TCF3, ZBTB7A

miRNA regulators (miRDB)

Targeting COMP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

3 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-3909	97.55	66.78	887

Functional genomics

gnomAD constraint: pLI 1.64e-24, LOEUF 1.07, missense Z 1.51 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000222271 — one region, missense o/e 0.84. ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Disease-causing mutations in cartilage oligomeric matrix protein cause an unstructured Ca2+ binding domain (PMID:11782471)
• Mutations effect the matrix around chondrocytes, causing osteochondrodysplasias (PMID:11891674)
• Matrix-matrix interaction of cartilage oligomeric matrix protein and fibronectin. (PMID:12225811)
• COMP gene mutations have been identified in patients with pseudochondrodysplasia and multiple epiphyseal dysplasia. (PMID:12768438)
• Mutations of the cartilage oligomeric matrix protein gene is associated with pseudoachondroplasia (PMID:12792737)
• Data show that mutated cartilage oligomeric matrix protein accumulated in the rough endoplasmic reticulum, and the affected cells were more likely to undergo apoptosis. (PMID:12819015)
• COMP expression is up-regulated by both GH and IGF-I in primary cultured human chondrocytes (PMID:15472220)
• COMP, type IX collagen and MATN3 play important roles in matrix assembly (PMID:15694129)
• COMP secretion is affected by the signal peptide (PMID:15749701)
• Mapping of all known COMP C-terminal domain (CTD) mutations on a three-dimensional model shows that the CTD mutations cluster in two distinct regions. (PMID:15880723)
• COMP/TSP5 can mediate chondrocyte attachment through interactions with integrins (PMID:16051604)
• expression pattern of both promoters recapitulates endogenous cartilage COMP expression in mice (PMID:16214313)
• COMP encodes a noncollagenous extracellular matrix protein in various musculoskeletal tissues {review} (PMID:16340129)
• COMP is overexpressed in scleroderma skin and cultured fibroblasts possibly due to autocrine TGFbeta stimulation, and COMP overexpression is sufficient to stimulate excess matrix deposition (PMID:16520029)
• COMP might be involved in human limb development, is upregulated in osteoarthritis (OA), and could play a role in the pathogenesis of OA as a factor secreted by chondrocytes to ameliorate the matrix breakdown. (PMID:16542502)
• This study showed that heritable factors influence serum levels of the cartilage matrix biomarker cartilage oligomeric matrix protein (COMP) in osteoarthritis. (PMID:16802351)
• May play an important role in an attempted repair of either traumatized or degenerated cartilage. (PMID:17033713)
• The results demonstrate that different COMP mutations in the T3 repeat domain have variable effects on intracellular transport, which correlate with clinical severity (PMID:17570134)
• DNA sequencing-based genetic diagnosis of pseudoachondroplasia revealed a heterozygous mutation for the nucleotide change 1532A>G in exon 14 of the COMP gene, resulting in a substitution of amino acid 511 from aspartic acid to glycine. (PMID:17579668)
• COMP/TSP5 may function to support matrix interactions with aggrecan in cartilage extracellular matrix (PMID:17588949)
• the authors consider serum COMP levels in different diseases…and discuss…whether COMP is able to predict a rapid and sustained clinical response to anti-TNF-alpha drugs. (PMID:17894003)
• Data show COMP protects cells against death by elevating members of the IAP family of survival proteins. (PMID:17993464)
• COMP mutations are associated with skeletal dysplasias (PMID:18193163)
• Recent studies highlighted in this review have identified molecular functions of cartilage oligomeric matrix protein that may contribute to its role in skeletal disease. (PMID:18855621)
• there is an inverse relationship between hypermobility and hand and knee osteoarthritis, and that hypermobility is associated with lower serum COMP levels (PMID:19035482)
• COMP, CXCL9 and KRT19 play an important role in the pathopoiesis of oral submucosal fibrosis. (PMID:19087608)
• Serum COMP was increased 1.6-fold at 10 km during a marathon race and declined to the pre-race level after 2 days recovery. (PMID:19125286)
• The crystal packing reveals an exposed potential metal-ion-dependent adhesion site on one edge of the beta-sandwich that is common to all TSPs and may serve as a binding site for collagens and other ligands. (PMID:19276170)
• Elevation of COMP may reflect joint damage that is dependent on the synovial inflammatory process in early-stage rheumatoid arthritis. (PMID:19447929)
• We found reduced COMP levels in children with juvenile idiopathic arthritis compared with healthy children (PMID:19605679)
• The structure of the mutant COMP growth plate recapitulated the findings of human pseudoachondroplasia growth plate morphology. (PMID:19762713)
• Serum COMP levels correlated with total-body joint disease severity as determined by bone scintigraphy, supporting the idea that whole-body bone scintigraphy quantifies the total-body burden of osteoarthritis for systemic biomarker validation. (PMID:19877068)
• Data show that cartilage oligomeric matrix protein (COMP) promotes cell attachment via independent mechanisms involving cell surface CD47 and alphaVbeta3 integrin and that cell attachment to COMP induces formation of fascin-stabilized actin microspikes. (PMID:20033473)
• Elevation of COMP serum concentration seems to depend on the loading mode of the physical activity and to reflect the extrusion of COMP fragments from the impact loaded articular cartilage or synovial fluid. (PMID:20544356)
• Mutations in COMP gene are responsible for the pseudoachondroplasia. Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of pseudoachondroplasia. (PMID:20819661)
• Data revealed a strong induction of several genes encoding components of the extracellular matrix, such as collagens, COMP, IGFBP5 and biglycan. (PMID:21029365)
• We report an 81% mutation detection rate for pseudoachondroplasia, of which COMP+Col9A3 mutations were more prevalent (61%) than COMP mutations alone (30%). (PMID:21042783)
• The results suggest that uCTX-I, uCTX-II and sCOMP could identify patients with focal cartilage lesions from an early stage of osteoarthritis of the knee. (PMID:21221577)
• a c. 1352_1353ins TGTCCCTGG is a novel mutation in COMP responsible for severe familial pseudoachondroplasia (PMID:21599986)
• In vivo exercise interventions differentially regulate serum COMP concentrations and knee cartilage deformations. The relation between changes in COMP and in cartilage volume seems to depend on both mechanical and biochemical factors. (PMID:21616158)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	comp	ENSDARG00000098431
mus_musculus	Comp	ENSMUSG00000031849
rattus_norvegicus	Comp	ENSRNOG00000048472
drosophila_melanogaster	Tsp	FBGN0031850

Paralogs (5): ISM1 (ENSG00000101230), THBS4 (ENSG00000113296), THBS1 (ENSG00000137801), THBS3 (ENSG00000169231), THBS2 (ENSG00000186340)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88469) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal chondrocyte morphology	2
decreased body weight	2
disproportionate dwarf	2
short tibia	2
abnormal long bone epiphyseal plate proliferative zone	2
abnormal pelvic girdle bone morphology	2
abnormal hip joint morphology	2
abnormal cartilage morphology	1
short limbs	1
myopathy	1
abnormal long bone epiphyseal plate morphology	1
decreased tendon stiffness	1
short femur	1
osteoarthritis	1
increased muscle fatigability	1
abnormal ischium morphology	1
abnormal vascular wound healing	1
abnormal tendon morphology	1
centrally nucleated skeletal muscle fibers	1
abnormal chondrocyte physiology	1
decreased grip strength	1
decreased chondrocyte proliferation	1
increased chondrocyte apoptosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q7YQD7	98.0%	Diamond
Bos taurus	Q28178	97.1%	Diamond
Xenopus laevis	P35448	80.9%	Diamond
Gallus gallus	P35440	80.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
COPE	protein-coding	11316
GDF1	protein-coding	2657
DDX49	protein-coding	54555
UPF1	protein-coding	5976
CRTC1	protein-coding	23373
TMEM59L	protein-coding	25789
KLHL26	protein-coding	55295
CERS1	protein-coding	10715

Protein

Protein identifiers

Cartilage oligomeric matrix protein — P49747 (reviewed: P49747)

Alternative names: Thrombospondin-5

All UniProt accessions (2): G3XAP6, P49747

UniProt curated annotations — full annotation on UniProt →

Function. Plays 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.

Subunit / interactions. Pentamer; disulfide-linked. Exists in a more compact conformation in the presence of calcium and shows a more extended conformation in the absence of calcium. Interacts with ITGB3, ITGA5 and FN1. Binding to FN1 requires the presence of divalent cations (Ca(2+), Mg(2+) or Mn(2+)). The greatest amount of binding is seen in the presence of Mn(2+). Interacts with MATN1, MATN3, MATN4 and ACAN. Binds heparin, heparan sulfate and chondroitin sulfate. EDTA dimishes significantly its binding to ACAN and abolishes its binding to MATN3, MATN4 and chondroitin sulfate. Interacts with collagen I, II and IX, and interaction with these collagens is dependent on the presence of zinc ions. Interacts with ADAMTS12. Interacts with ITGA7.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Abundantly expressed in the chondrocyte extracellular matrix, and is also found in bone, tendon, ligament and synovium and blood vessels. Increased amounts are produced during late stages of osteoarthritis in the area adjacent to the main defect.

Post-translational modifications. Proteolytically cleaved by metalloproteases ADAMTS4 and ADAMTS1 with ADAMTS4 showing more potent activity.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. Carpal tunnel syndrome 2 (CTS2) [MIM:619161] An autosomal dominant form of carpal tunnel syndrome, a condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 11-14 calcium ions per subunit.

Domain organisation. The cell attachment motif mediates the attachment to chondrocytes. It mediates the induction of both the IAP family of survival proteins and the antiapoptotic response. The TSP C-terminal domain mediates interaction with FN1 and ACAN. Each of the eight TSP type-3 repeats binds two calcium ions. The TSP C-terminal domain binds three calcium ions.

Similarity. Belongs to the thrombospondin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49747-1	1	yes
P49747-2	2

RefSeq proteins (1): NP_000086* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR003367	Thrombospondin_3-like_rpt	Repeat
IPR008859	Thrombospondin_C	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017897	Thrombospondin_3_rpt	Repeat
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR024665	TSP/COMP_CC	Domain
IPR028974	TSP_type-3_rpt	Homologous_superfamily
IPR039081	TSP-5_CC	Domain
IPR046970	TSP/COMP_CC_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain

Pfam: PF02412, PF05735, PF07645, PF11598

UniProt features (184 total): sequence variant 81, strand 34, disulfide bond 23, helix 12, repeat 8, turn 6, domain 5, region of interest 3, compositionally biased region 3, sequence conflict 2, glycosylation site 2, signal peptide 1, chain 1, short sequence motif 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
3FBY	The crystal structure of the signature domain of cartilage oligomeric matrix protein.	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49747-F1	88.60	0.67

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the musculoskeletal system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
77–78	cleavage; by adamts4

Disulfide bonds (23)

Type	Positions
Interchain	69, 72
Disulfide bond	91–102, 96–111, 114–125, 131–142, 136–151, 154–178, 184–197, 191–206, 209–221, 229–243, 237–253, 255–266, 282–287, 292–312, 328–348, 351–371, 387–407, 410–430, 448–468, 484–504, 520–741

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	121, 742

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-3000178	ECM proteoglycans	curated
R-HSA-216083	Integrin cell surface interactions	curated
R-HSA-1474244	Extracellular matrix organization	—

MSigDB gene sets: 388 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_PLATELET_ACTIVATION, MODULE_45, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GOBP_ARTERY_DEVELOPMENT, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT

GO Biological Process (9): skeletal system development (GO:0001501), apoptotic process (GO:0006915), cell adhesion (GO:0007155), animal organ morphogenesis (GO:0009887), negative regulation of apoptotic process (GO:0043066), protein homooligomerization (GO:0051260), limb development (GO:0060173), cartilage homeostasis (GO:1990079), collagen fibril organization (GO:0030199)

GO Molecular Function (10): protease binding (GO:0002020), integrin binding (GO:0005178), extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), collagen binding (GO:0005518), heparin binding (GO:0008201), BMP binding (GO:0036122), proteoglycan binding (GO:0043394), heparan sulfate proteoglycan binding (GO:0043395), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), thrombospondin complex (GO:1990341), protein-containing complex (GO:0032991)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Extracellular matrix organization	2

GO top-level categories

35 GO namespaces:

Category	Terms
protein-containing complex binding	2
system development	1
animal gross anatomical part developmental process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
anatomical structure morphogenesis	1
animal organ development	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
protein complex oligomerization	1
appendage development	1
tissue homeostasis	1
extracellular matrix organization	1
enzyme binding	1
signaling receptor binding	1
cell adhesion molecule binding	1
structural molecule activity	1
extracellular matrix	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
cytokine binding	1
protein binding	1
carbohydrate derivative binding	1
proteoglycan binding	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1
extracellular vesicle	1
non-collagenous component of interstitial matrix	1
extracellular protein-containing complex	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
cartilage homeostasis	BP	direct assay
limb development	BP	direct assay
negative regulation of apoptotic process	BP	direct assay
protein homooligomerization	BP	direct assay
extracellular exosome	CC	high-throughput assay
extracellular matrix	CC	direct assay
extracellular region	CC	direct assay
calcium ion binding	MF	direct assay
collagen binding	MF	direct assay
heparan sulfate proteoglycan binding	MF	direct assay
heparin binding	MF	direct assay
protease binding	MF	physical interaction
proteoglycan binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,296 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COMP	ACAN	P16112	823
COMP	MATN3	O15232	767
COMP	COL2A1	P02458	687
COMP	FMOD	Q06828	687
COMP	COL9A3	Q14050	681
COMP	ADAMTS7	Q9UKP4	677
COMP	DCN	P07585	676
COMP	COL9A2	Q14055	672
COMP	HAPLN1	P10915	659
COMP	MMP13	P45452	639
COMP	MTX1	Q13505	613
COMP	PRG4	Q92954	604
COMP	CRP	P02741	598
COMP	MMP3	P08254	598
COMP	BGN	P13247	597

IntAct

Human interaction partners of COMP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
OTX1	physical association	0.780	7
ADAMTS12	physical association	0.680	3
AQP1	physical association	0.560	3
ATOX1	physical association	0.560	3
CYSRT1	physical association	0.560	3
MEOX2	physical association	0.560	3
NUFIP2	physical association	0.560	3
SGTB	physical association	0.560	3
ACAN	direct interaction	0.440	2
ADAMTS7	protein cleavage	0.440	1
MATN3	direct interaction	0.440	1
VHL	physical association	0.400	1
P4HB	association	0.350	2
STAT3	association	0.350	1

BioGRID (15 interactions; top human partners by supporting records): OTX1 (Two-hybrid; 2 records), AQP1 (Two-hybrid), ATOX1 (Two-hybrid), C12orf49 (Negative Genetic), CYSRT1 (Two-hybrid), MATN2 (Affinity Capture-MS), MEOX2 (Two-hybrid), NUFIP2 (Two-hybrid), SGTB (Two-hybrid), SOX2 (Affinity Capture-MS), STAT3 (Affinity Capture-MS), UBE2H (Affinity Capture-MS), VHL (Affinity Capture-MS), XIAP (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for COMP: 927 ClinVar records (142 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

927 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	88
Uncertain significance	421
Likely benign	212
Benign	37

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 142 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
40988	NM_000095.3(COMP):c.1405GAC[4] (p.Asp473del)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
40995	NM_000095.3(COMP):c.1754C>T (p.Thr585Met)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
988295	NM_000095.3(COMP):c.1201G>A (p.Asp401Asn)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1180714	NM_000095.3(COMP):c.1403G>T (p.Cys468Phe)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1723871	NM_000095.3(COMP):c.1045G>C (p.Asp349His)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2138263	NM_000095.3(COMP):c.1423G>A (p.Asp475Asn)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
449474	NM_000095.3(COMP):c.1195G>A (p.Asp399Asn)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
818216	NM_000095.3(COMP):c.1309G>A (p.Asp437Asn)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1327423	NM_000095.3(COMP):c.1501G>A (p.Gly501Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
618040	NM_000095.3(COMP):c.1675G>A (p.Glu559Lys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
803550	NM_000095.3(COMP):c.818A>T (p.Asp273Val)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1510817	NM_000095.3(COMP):c.1153_1155del (p.Asp385del)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2138264	NM_000095.3(COMP):c.1372G>T (p.Asp458Tyr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2444368	NM_000095.3(COMP):c.1316A>G (p.Asp439Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3723496	NM_000095.3(COMP):c.1450T>G (p.Cys484Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore COMP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 1,264):

Position(s)	Effect	Δscore	Sites
19:18783052–18783053	donor_loss	1.0000	5
19:18784887	donor_gain	1.0000
19:18784894–18784895	donor_loss	1.0000	4
19:18784943	donor_gain	1.0000
19:18785093	acceptor_loss	1.0000
19:18785099	acceptor_gain	1.0000
19:18785671–18785672	donor_loss	1.0000	5
19:18786147–18786148	acceptor_loss	1.0000	5
19:18787651	acceptor_gain	1.0000
19:18787651–18787652	acceptor_loss	1.0000	3

AlphaMissense

2,362 missense substitutions predicted likely pathogenic (of 5,062 scored), across 478 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M613	9	0.837	0.981
D595	8	0.996	0.999
D593	8	0.994	0.998
F727	8	0.993	1.000
D290	8	0.992	0.998
D567	8	0.992	0.997
D269	8	0.991	0.997
D271	8	0.991	0.995
D273	8	0.990	0.996
D437	8	0.989	0.997
D446	8	0.988	0.997
D518	8	0.988	0.994
D540	8	0.988	0.995
D439	8	0.986	0.996
D435	8	0.985	0.996
D349	8	0.982	0.996
D326	8	0.981	0.996
D482	8	0.981	0.995
D509	8	0.981	0.991
D317	8	0.976	0.989

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Pancreatic Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000341

Disease associations

OMIM: gene MIM:600310 | disease phenotypes: MIM:132400, MIM:177170, MIM:619161

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
pseudoachondroplasia	Definitive	Autosomal dominant	4
COMP-related skeletal dysplasia	Definitive	Autosomal dominant
multiple epiphyseal dysplasia type 1	Strong	Autosomal dominant	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
COMP-related skeletal dysplasia	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Fetal anomalies	green
Multiple Epiphyseal Dysplasia	green
Paediatric disorders	green
Skeletal dysplasia	green

Mondo (5): multiple epiphyseal dysplasia type 1 (MONDO:0007561), pseudoachondroplasia (MONDO:0008322), multiple epiphyseal dysplasia (MONDO:0016648), carpal tunnel syndrome 2 (MONDO:0030883), COMP-related skeletal dysplasia (MONDO:0100593)

Orphanet (3): Multiple epiphyseal dysplasia type 1 (Orphanet:93308), Pseudoachondroplasia (Orphanet:750), Multiple epiphyseal dysplasia (Orphanet:251)

HPO phenotypes

showing 60 of 93 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000763	Sensory neuropathy
HP:0000926	Platyspondyly
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001288	Gait disturbance
HP:0001376	Limitation of joint mobility
HP:0001377	Limited elbow extension
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001387	Joint stiffness
HP:0001498	Carpal bone hypoplasia
HP:0001763	Pes planus
HP:0002341	Cervical cord compression
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002656	Epiphyseal dysplasia
HP:0002663	Delayed epiphyseal ossification
HP:0002758	Osteoarthritis
HP:0002761	Generalized joint hypermobility
HP:0002808	Kyphosis
HP:0002812	Coxa vara
HP:0002816	Genu recurvatum
HP:0002829	Arthralgia
HP:0002834	Flared femoral metaphysis
HP:0002857	Genu valgum
HP:0002938	Lumbar hyperlordosis
HP:0002970	Genu varum
HP:0003015	Flared metaphysis
HP:0003016	Metaphyseal widening
HP:0003025	Metaphyseal irregularity
HP:0003026	Short long bone
HP:0003049	Ulnar deviation of the wrist
HP:0003090	Hypoplasia of the capital femoral epiphysis
HP:0003093	Limited hip extension
HP:0003170	Abnormal acetabulum morphology
HP:0003180	Flat acetabular roof
HP:0003300	Ovoid vertebral bodies
HP:0003301	Irregular vertebral endplates
HP:0003311	Hypoplasia of the odontoid process
HP:0003312	Abnormal vertebral body morphology
HP:0003365	Arthralgia of the hip
HP:0003393	Thenar muscle atrophy
HP:0003414	Atlantoaxial dislocation
HP:0003498	Disproportionate short stature
HP:0003502	Mild short stature
HP:0003510	Severe short stature
HP:0003756	Skeletal myopathy
HP:0004019	Radial metaphyseal irregularity
HP:0004042	Ulnar metaphyseal irregularity
HP:0004236	Irregular carpal bones
HP:0004568	Beaking of vertebral bodies
HP:0005063	Fragmented, irregular epiphyses
HP:0005720	Shortening of all metacarpals
HP:0005743	Avascular necrosis of the capital femoral epiphysis
HP:0006094	Finger joint hypermobility
HP:0006149	Increased laxity of fingers
HP:0006429	Broad femoral neck
HP:0006460	Ankle hypermobility
HP:0006467	Limited shoulder movement

GWAS associations

3 associations:

Study	Trait	p-value
GCST004199_2	Osteoarthritis (with total hip replacement)	4e-12
GCST005171_40	QT interval	3e-6
GCST002540_3	Osteoarthritis biomarkers	7e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0005890	osteoarthritis biomarker measurement
EFO:0007942	hip osteoarthritis symptom severity measurement
EFO:0004682	QT interval

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C535819	Pseudoachondroplasia *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression, affects expression	4
Valproic Acid	affects expression, increases expression	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Estradiol	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
N-((3,5-difluorophenyl)acetyl)alanyl-2-phenylglycine-1,1-dimethylethyl ester	increases expression	1
2,4,6-tribromophenol	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
HT-2 toxin	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
corosolic acid	increases expression	1
abrine	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
incobotulinumtoxinA	increases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Aluminum Oxide	increases expression	1
Calcitriol	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Ivermectin	decreases expression	1
Urethane	increases expression	1
Zinc	increases expression	1
Cyclosporine	increases expression	1
Asbestos, Crocidolite	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 84 trials:

NCT	Phase	Status	Title
NCT01042158	Phase 4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	Phase 4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	Phase 4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	Phase 4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	Phase 4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	Phase 4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	Phase 4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00864201	Phase 3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	Phase 3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	Phase 3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	Phase 3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	Phase 3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT06716606	Phase 3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	Phase 3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT03866200	Phase 2	TERMINATED	Resveratrol Trial for Relief of Pain in Pseudoachondroplasia
NCT00004357	Phase 2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	Phase 2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	Phase 2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	Phase 2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	Phase 2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	Phase 2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	Phase 2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	Phase 2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01093911	Phase 1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	Phase 1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	Phase 1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	Phase 1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	Phase 1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT01424033	Phase 2/3	TERMINATED	A Clinical Trial for CTD-ILD Treatment
NCT04915482	Phase 2/3	UNKNOWN	TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT06574581	Phase 1/2	RECRUITING	ADSCs Therapy in Patients With CTD-ILD
NCT00001330	Not specified	COMPLETED	Study of Silicone-Associated Connective Tissue Diseases
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00001978	Not specified	TERMINATED	Determination of Kidney Function
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease
NCT00341679	Not specified	COMPLETED	Studies of the Natural History and Pathogenesis of Autoimmune/Connective Tissue Diseases
NCT00470327	Not specified	RECRUITING	A Study of the Natural Progression of Interstitial Lung Disease (ILD)
NCT00491309	Not specified	UNKNOWN	Exercise and Respiratory Therapy in Patients With Rheumatoid Arthritis / Collagenosis and Pulmonary Hypertension
NCT00522002	Not specified	COMPLETED	CLUE Study: Connective Tissue Disease Leg Ulcer Etiology Study
NCT00802607	Not specified	TERMINATED	Collection of Tissue Specimens for Analysis and Establishment of Cell Cultures
NCT01208792	Not specified	COMPLETED	Auto-immunity and Pulmonary Arterial Hypertension
NCT01379118	Not specified	COMPLETED	Comparison of Clinical Outcomes and Performance of Total Knee Replacement Patients Before and After Surgery
NCT01387035	Not specified	UNKNOWN	Early Diagnosis of Pulmonary Hypertension in Patients With Inflammatory Rheumatic Connective Tissue Diseases
NCT01656278	Not specified	COMPLETED	An MRI-guided Treatment Strategy to Prevent Disease Progression in Patients With Rheumatoid Arthritis
NCT01809574	Not specified	UNKNOWN	The Role of Rheumatological Evaluation in the Management of Patients With Interstitial Lung Disease
NCT02768259	Not specified	UNKNOWN	Prevalence of Pulmonary Arterial Hypertension in Patients With Connective Tissue Diseases in Egyptian Patients
NCT03214263	Not specified	UNKNOWN	Identification of New Biomarkers to Promote Personalized Treatment of Patients With Inflammatory Rheumatic Diseases
NCT03446339	Not specified	UNKNOWN	Pulmonary Hypertension Screening for Rheumatology Patients (SOPHIE)
NCT03494036	Not specified	COMPLETED	Effect of Synbiotic on Immune Response, Gut Permeability and Microbiota in Patient With Connective Tissue Disease
NCT03565601	Not specified	UNKNOWN	Prognostic Value of Anti-Ro52 Antibodies in Connective Tissue Diseases (a-Ro52)
NCT03847753	Not specified	COMPLETED	Exploring the Comorbidity Between Mental Disorders and General Medical Conditions
NCT04095351	Not specified	RECRUITING	Connective Tissue Diseases and Lung Manifestations
NCT04171362	Not specified	COMPLETED	The Effect of Connective Tissue Massage in Patients With Migraine
NCT04297371	Not specified	COMPLETED	Early Detection of Cardiac Impairment and Prediction of RV Hypertrophy in Patients With CTD
NCT04398628	Not specified	RECRUITING	ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
NCT04428957	Not specified	UNKNOWN	Telemonitoring of Treatment Effects in Connective Tissue Disease-associated Interstitial Lung Disease (TEL-CTD-ILD)
NCT04582292	Not specified	UNKNOWN	Laryngeal Manifestations of Connective Tissue Diseases
NCT04664478	Not specified	COMPLETED	Gene First Approach to Connective Tissue Disease