COMP (cartilage oligomeric matrix protein)

Gene

• Entrez ID: 1311
• Gene name: Cartilage oligomeric matrix protein
• Gene symbol: COMP
• Synonyms (NCBI Gene): CTS2, EDM1, EPD1, MED, PSACH, THBS5, TSP-5, TSP5
• Chromosome: 19
• Chromosome location: 19p13.11
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28936368	G>A,T	Benign, pathogenic	Synonymous variant, coding sequence variant, missense variant
rs28936668	T>C	Pathogenic	Coding sequence variant, missense variant
rs28936669	T>C	Pathogenic	Coding sequence variant, missense variant
rs137852650	C>A	Pathogenic	Coding sequence variant, missense variant
rs137852651	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852652	C>A	Pathogenic	Coding sequence variant, missense variant
rs137852653	A>G	Pathogenic	Coding sequence variant, missense variant
rs137852654	G>C,T	Likely-pathogenic	Coding sequence variant, missense variant
rs137852655	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852656	A>G	Pathogenic	Coding sequence variant, missense variant
rs149551600	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs193922900	TCG>-,TCGTCG,TCGTCGTCG	Pathogenic, pathogenic-likely-pathogenic	Inframe insertion, coding sequence variant, inframe deletion
rs312262899	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs312262900	G>A,C,T	Pathogenic	Missense variant, coding sequence variant
rs312262901	T>C	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs312262903	G>A	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs312262904	C>T	Pathogenic	Missense variant, coding sequence variant
rs374063820	A>G	Conflicting-interpretations-of-pathogenicity	Intron variant
rs397515510	TGT>-	Pathogenic	Inframe deletion, coding sequence variant
rs397515511	G>T	Pathogenic	Coding sequence variant, missense variant
rs397515512	C>T	Pathogenic	Coding sequence variant, missense variant
rs397515513	G>C	Pathogenic	Coding sequence variant, missense variant
rs755374221	C>A,T	Likely-pathogenic	Splice donor variant
rs869320730	->G	Pathogenic	Frameshift variant, coding sequence variant
rs878853098	GCATCTCCCACAA>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs886041607	C>A	Pathogenic	Missense variant, coding sequence variant
rs886042932	C>G,T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1057521130	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1064794293	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1064794294	TCGTCC>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs1131691682	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1131691835	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1359984033	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs1555791425	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1555791490	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1555791556	C>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1568554484	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1568554988	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1601053887	CCT>-	Pathogenic	Inframe deletion, coding sequence variant
rs1601053997	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1601054002	C>A,T	Likely-pathogenic	Coding sequence variant, missense variant
rs1601054715	C>A	Pathogenic	Coding sequence variant, missense variant
rs1601055900	GCGCTGGTCTGGGTT>-	Likely-pathogenic	Inframe deletion, coding sequence variant
rs1601055923	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1601057057	T>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1601057167	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1601057491	T>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1601057570	A>G	Likely-pathogenic	Coding sequence variant, missense variant

Transcription factors

Transcription factor	Regulation	Reference
LRF	Unknown	15337766
SP1	Unknown	11223338

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	IEA
GO:0001501	Process	Skeletal system development	TAS	7670472
GO:0001503	Process	Ossification	IEA
GO:0002020	Function	Protease binding	IEA
GO:0002020	Function	Protease binding	IPI	18485748
GO:0002063	Process	Chondrocyte development	IEA
GO:0003416	Process	Endochondral bone growth	IEA
GO:0003417	Process	Growth plate cartilage development	IEA
GO:0005178	Function	Integrin binding	IEA
GO:0005201	Function	Extracellular matrix structural constituent	RCA	20551380
GO:0005201	Function	Extracellular matrix structural constituent	TAS	7713493
GO:0005509	Function	Calcium ion binding	IDA	10852928, 11084047
GO:0005509	Function	Calcium ion binding	IEA
GO:0005509	Function	Calcium ion binding	TAS	7670472
GO:0005515	Function	Protein binding	IPI	12225811, 15075323, 16051604, 16611630, 17588949, 18485748, 25416956, 31515488, 32296183
GO:0005518	Function	Collagen binding	IDA	11084047
GO:0005576	Component	Extracellular region	HDA	27068509
GO:0005576	Component	Extracellular region	IDA	32747625
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	HDA	20551380
GO:0005615	Component	Extracellular space	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0006986	Process	Response to unfolded protein	IEA
GO:0007155	Process	Cell adhesion	IEA
GO:0007596	Process	Blood coagulation	IEA
GO:0008201	Function	Heparin binding	IDA	17588949
GO:0008201	Function	Heparin binding	IEA
GO:0009306	Process	Protein secretion	IEA
GO:0009887	Process	Animal organ morphogenesis	TAS	7713493
GO:0010468	Process	Regulation of gene expression	IEA
GO:0014829	Process	Vascular associated smooth muscle contraction	IEA
GO:0016485	Process	Protein processing	IEA
GO:0030199	Process	Collagen fibril organization	IEA
GO:0030282	Process	Bone mineralization	IEA
GO:0030500	Process	Regulation of bone mineralization	IEA
GO:0030509	Process	BMP signaling pathway	IEA
GO:0031012	Component	Extracellular matrix	HDA	20551380
GO:0031012	Component	Extracellular matrix	IBA
GO:0031012	Component	Extracellular matrix	IDA	18285447
GO:0031012	Component	Extracellular matrix	TAS	7713493
GO:0032991	Component	Protein-containing complex	IEA
GO:0035264	Process	Multicellular organism growth	IEA
GO:0035988	Process	Chondrocyte proliferation	IEA
GO:0035989	Process	Tendon development	IEA
GO:0036122	Function	BMP binding	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IDA	17993464
GO:0043394	Function	Proteoglycan binding	IDA	29030641
GO:0043395	Function	Heparan sulfate proteoglycan binding	IDA	17588949
GO:0043588	Process	Skin development	IEA
GO:0048844	Process	Artery morphogenesis	IEA
GO:0050881	Process	Musculoskeletal movement	IEA
GO:0050905	Process	Neuromuscular process	IEA
GO:0051216	Process	Cartilage development	IEA
GO:0051260	Process	Protein homooligomerization	IDA	32747625
GO:0051260	Process	Protein homooligomerization	IEA
GO:0055001	Process	Muscle cell development	IEA
GO:0060173	Process	Limb development	IDA	16542502
GO:0060173	Process	Limb development	IEA
GO:0060349	Process	Bone morphogenesis	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0070527	Process	Platelet aggregation	IEA
GO:0090398	Process	Cellular senescence	IEA
GO:0097084	Process	Vascular associated smooth muscle cell development	IEA
GO:0098868	Process	Bone growth	IEA
GO:1900047	Process	Negative regulation of hemostasis	IEA
GO:1902732	Process	Positive regulation of chondrocyte proliferation	IEA
GO:1990079	Process	Cartilage homeostasis	IDA	32747625
GO:1990079	Process	Cartilage homeostasis	IEA

Other IDs

• MIM: 600310
• HGNC: 2227
• e!Ensembl: ENSG00000105664

Protein

• UniProt ID: P49747
• Protein name: Cartilage oligomeric matrix protein (COMP) (Thrombospondin-5) (TSP5)
• Protein 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
• PDB: 3FBY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF11598	COMP	29 → 73	Cartilage oligomeric matrix protein	Family
  PF07645	EGF_CA	127 → 178	Calcium-binding EGF domain	Domain
  PF07645	EGF_CA	180 → 221	Calcium-binding EGF domain	Domain
  PF02412	TSP_3	301 → 336	Thrombospondin type 3 repeat	Repeat
  PF02412	TSP_3	360 → 395	Thrombospondin type 3 repeat	Repeat
  PF02412	TSP_3	395 → 418	Thrombospondin type 3 repeat	Repeat
  PF02412	TSP_3	419 → 456	Thrombospondin type 3 repeat	Repeat
  PF02412	TSP_3	457 → 492	Thrombospondin type 3 repeat	Repeat
  PF02412	TSP_3	493 → 528	Thrombospondin type 3 repeat	Repeat
  PF05735	TSP_C	546 → 743	Thrombospondin C-terminal region	Family

• Tissue specificity: 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 m
• Sequence:

  MVPDTACVLLLTLAALGASGQGQSPLGSDLGPQMLRELQETNAALQDVRELLRQQVREIT
  FLKNTVMECDACGMQQSVRTGLPSVRPLLHCAPGFCFPGVACIQTESGARCGPCPAGFTG
  NGSHCTDVNECNAHPCFPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAFAKANKQVCTD
  INECETGQHNCVPNSVCINTRGSFQCGPCQPGFVGDQASGCQRRAQRFCPDGSPSECHEH
  ADCVLERDGSRSCVCAVGWAGNGILCGRDTDLDGFPDEKLRCPERQCRKDNCVTVPNSGQ
  EDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQK
  DTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQAD
  VDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDGVPDS
  RDNCRLVPNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLD
  PEGDAQIDPNWVVLNQGREIVQTMNSDPGLAVGYTAFNGVDFEGTFHVNTVTDDDYAGFI
  FGYQDSSSFYVVMWKQMEQTYWQANPFRAVAEPGIQLKAVKSSTGPGEQLRNALWHTGDT
  ESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPELVADSNVVLDTTMRGG
  RLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQA

• Sequence length: 757

Pathways

KEGG:

Phagosome
PI3K-Akt signaling pathway
Focal adhesion
ECM-receptor interaction
Cytoskeleton in muscle cells
Malaria
Human papillomavirus infection

Reactome:

Integrin cell surface interactions
ECM proteoglycans

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the skeletal system	Pathogenic	rs137852651	RCV001814443	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Carpal tunnel syndrome 2	Likely pathogenic; Pathogenic	rs28936368, rs1555791490, rs312262900, rs1601054715, rs2055205599	RCV001289465 RCV004796224 RCV002496507 RCV002504388 RCV001289466	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
COMP-related disorder	Likely pathogenic; Pathogenic	rs2145902345, rs2145902131, rs2145900919, rs368273443, rs28933699, rs312262900, rs1601059597	RCV005868370 RCV004754819 RCV004754813 RCV003404620 RCV003894158 RCV004754281 RCV004545810	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Epiphyseal dysplasia, multiple, 1, severe	Pathogenic	rs137852652, rs28936668	RCV000009765 RCV000009768	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Multiple epiphyseal dysplasia	Likely pathogenic; Pathogenic	rs2145900523, rs137852654, rs193922900, rs28936368, rs312262900, rs149551600, rs1601054715	RCV001787703 RCV002054430 RCV002054431 RCV002054432 RCV002054552 RCV002054553 RCV002054897 RCV002069395	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple epiphyseal dysplasia type 1	Likely pathogenic; Pathogenic	rs368273443, rs2145901302, rs2145900523, rs2145902345, rs2055169002, rs1198060288, rs1555791556, rs2145897697, rs2145900873, rs2145903160, rs397515511, rs1601057491, rs137852654, rs193922900, rs137852655, rs869320730, rs28936368, rs312262903, rs2512847828, rs1555791490, rs312262900, rs1568554988, rs1601054002, rs1601057167, rs1601054715, rs2055184939, rs137852651	RCV003232336 RCV001730047 RCV002236174 RCV001806396 RCV001823667 RCV002290796 RCV002221407 RCV002238714 RCV002238718 RCV002249014 RCV002288301 RCV002790043 RCV000009767 RCV000009771 RCV003989283 RCV000009775 RCV000009776 RCV003990350 RCV004006238 RCV000505823 RCV004796224 RCV001332185 RCV002496507 RCV000761229 RCV000853301 RCV000853323 RCV000995526 RCV001805971 RCV001810013 RCV001270873	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pseudoachondroplasia, severe	Likely pathogenic; Pathogenic	rs137852655	RCV000009772	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome	Likely pathogenic; Pathogenic	rs2145903203, rs2145902336, rs1198060288, rs2145903433, rs2145903238, rs2145900849, rs2145903266, rs2145903243, rs2145902239, rs2055165476, rs2145900494, rs2055161717, rs2145902248, rs2512847668, rs137852650, rs2145900868, rs137852653, rs28936669, rs193922900, rs137852655, rs137852656, rs2145902395, rs2512847519, rs1555791556, rs1555791490, rs312262900, rs312262901, rs312262904, rs1359984033, rs1601054002, rs1601057491, rs1601053887, rs2055164276, rs2055164523, rs2055169002, rs2055184939, rs1601054715, rs2055168912	RCV001806405 RCV001806420 RCV002259406 RCV005868440 RCV005253917 RCV002227890 RCV002227954 RCV002238715 RCV002240139 RCV002240141 RCV002238716 RCV002306428 RCV002306432 RCV003153166 RCV000009761 RCV000009763 RCV000009766 RCV000009769 RCV000033881 RCV000033890 RCV000009773 RCV000009774 RCV003234856 RCV000505823 RCV004796224 RCV000033880 RCV000033886 RCV000033887 RCV000033888 RCV000033889 RCV000990188 RCV000990189 RCV000990191 RCV000995525 RCV001250922 RCV001250926 RCV001250924 RCV001250925 RCV002504388 RCV001293718	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMP-RELATED SKELETAL DYSPLASIA	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ANOMALY OF CARTILAGE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONNECTIVE TISSUE DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Connective tissue disorder	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPIPHYSEAL DYSPLASIA, MULTIPLE, 1	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple Epiphyseal Dysplasia, Dominant	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS OF HIP	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, HIP	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOCHONDRODYSPLASIAS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult Medulloblastoma	Medulloblastoma	BEFREE	15367707, 21720807, 24756834, 2478022		★☆☆☆☆ Found in Text Mining only
Alkaptonuria	Alkaptonuria	BEFREE	28028161		★☆☆☆☆ Found in Text Mining only
alpha-Thalassemia	alpha Thalassemia	BEFREE	10973135, 11378664, 12028055, 1520607, 22924376		★☆☆☆☆ Found in Text Mining only
alpha^+^ Thalassemia	alpha Thalassemia	BEFREE	10973135, 11378664, 12028055, 1520607, 22924376		★☆☆☆☆ Found in Text Mining only
Anaplasia	Anaplasia	BEFREE	12678339		★☆☆☆☆ Found in Text Mining only
Androgen-Insensitivity Syndrome	Androgen-Insensitivity Syndrome	BEFREE	28951969		★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm	Aortic Aneurysm	BEFREE	28849199		★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm	Aortic aneurysm	Pubtator	28849199	Inhibit	★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	23415669, 28155614, 28849199, 31495329		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	18576344, 20506400, 26696755, 29030641, 29921387, 9844060		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	Pubtator	34680093	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Psoriatic	Psoriatic arthritis	Pubtator	18485748	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	15345499, 16761970, 34458379, 9714346	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis, Psoriatic	Psoriatic Arthritis	BEFREE	30910989		★☆☆☆☆ Found in Text Mining only
Arthropathy	Arthropathy	BEFREE	28473207		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	29805540		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	23415669, 28155614, 28849199, 31495329		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	30643080		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	20859669		★☆☆☆☆ Found in Text Mining only
Avascular necrosis of the capital femoral epiphysis	Avascular Necrosis Of The Capital Femoral Epiphysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Barrett Esophagus	Barrett esophagus	Pubtator	34505128	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases Developmental	Bone disease	Pubtator	11087755	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases, Developmental	Bone Disease	BEFREE	18546327, 26377240		★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	20511364, 27065333, 29228690, 30231922, 30502484, 31737569		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	37229458	Stimulate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	40141111	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	30999932	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Basal Cell	Carcinoma	BEFREE	23507196		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	29530484		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Restrictive	Restrictive cardiomyopathy	Pubtator	24376648	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	BEFREE	28155614		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	27693578		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	31590967		★☆☆☆☆ Found in Text Mining only
Cartilage Diseases	Cartilage Diseases	BEFREE	17307347		★☆☆☆☆ Found in Text Mining only
Cartilage Diseases	Cartilage disease	Pubtator	22241609, 30721648	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar medulloblastoma	Cerebellar medulloblastoma	BEFREE	9420431		★☆☆☆☆ Found in Text Mining only
Cerebrovascular Disorders	Cerebrovascular disorder	Pubtator	28849199	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	15367707, 21720807, 24756834, 2478022		★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	37838792	Associate	★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	BEFREE	17570134, 18576344		★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	BEFREE	28038565		★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	BEFREE	28100410		★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	29610929		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	29560517, 30502262, 30995524, 31617091		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	BEFREE	31617091		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	36551305	Stimulate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	36671447, 37207219	Associate	★☆☆☆☆ Found in Text Mining only
Congenital genu recurvatum	Congenital genu recurvatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	28491082		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	Pubtator	23415669	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	28491082		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	28491082		★☆☆☆☆ Found in Text Mining only
Coronary Stenosis	Coronary Stenosis	BEFREE	28491082		★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	BEFREE	28114331, 30213581		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	10376735, 11238672, 11501943, 11691584, 16542502, 16802351, 17195216, 18291686, 20077500, 20187133, 21834907, 25057126, 25111190, 26162802, 26696755, 26818776, 28319091, 28373131, 28473207, 28507472, 28846474, 29030641, 29067461, 29530484, 30001809, 30208927, 30903650, 30910989, 31342791, 31352363, 31413818, 31575035, 9920012		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	LHGDN	16542502, 16802351		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	CTD_human_DG	7670472		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	30664617		★☆☆☆☆ Found in Text Mining only
Dermatitis	Dermatitis	BEFREE	29349514		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	30526057		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	25893345, 30526057		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	34813359	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	30526057, 31590967		★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic Retinopathy	BEFREE	26340930		★☆☆☆☆ Found in Text Mining only
Diastrophic dysplasia	Diastrophic dysplasia	Pubtator	10465113	Associate	★☆☆☆☆ Found in Text Mining only
Diastrophic dysplasia	Diastrophic Dysplasia	BEFREE	18553123, 8791509, 8879993		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	11691584, 12792737, 15472220, 20830670, 26377240		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism Pituitary	Pituitary dwarfism	Pubtator	33030144	Associate	★☆☆☆☆ Found in Text Mining only
Dysplastic Nevus	Dysplastic Nevus	BEFREE	8752657		★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	34686725, 37187159	Associate	★☆☆☆☆ Found in Text Mining only
Epiphyseal dysplasia	Epiphyseal dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epiphyseal dysplasia multiple 1	Epiphyseal dysplasia	Pubtator	9756911	Associate	★☆☆☆☆ Found in Text Mining only
Epiphyseal dysplasia, multiple, 1	Epiphyseal dysplasia	BEFREE	10405447, 11782471, 12819015, 9923655		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epiphyseal dysplasia, multiple, 1	Epiphyseal dysplasia	UNIPROT_DG	11084047, 11565064, 21922596, 7670472, 9021009, 9184241, 9452026, 9463320, 9921895		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epiphyseal dysplasia, multiple, 1	Epiphyseal dysplasia	CLINVAR_DG	15523498, 27330822, 7670472		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epiphyseal dysplasia, multiple, 1	Epiphyseal dysplasia	GENOMICS_ENGLAND_DG	17133256, 9021009		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epiphyseal dysplasia, multiple, 1	Epiphyseal dysplasia	CTD_human_DG	7670472, 9887340		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Erectile dysfunction	Erectile Dysfunction	BEFREE	29551532		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	28100410		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	9788574		★☆☆☆☆ Found in Text Mining only
Hamartomatous polyposis	Hamartomatous polyposis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hemoglobin H Disease	Hemoglobin H Disease	BEFREE	1642095		★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia, Familial	Hypercholesterolemia	BEFREE	17347910, 8828968, 8882879		★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	30526057, 31415078		★☆☆☆☆ Found in Text Mining only
Hyperlipoproteinemia Type IIa	Hyperlipoproteinemia	BEFREE	8828968, 8882879		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	30194545		★☆☆☆☆ Found in Text Mining only
Hyperuricemia	Hyperuricemia	BEFREE	25276832		★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Pulmonary Fibrosis	BEFREE	24376648, 29530484		★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis	Pubtator	24376648	Stimulate	★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	29228690		★☆☆☆☆ Found in Text Mining only
Intestinal Polyposis	Intestinal Polyposis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Juvenile arthritis	Arthritis	BEFREE	27385219, 31694747		★☆☆☆☆ Found in Text Mining only
Legg-Calve-Perthes Disease	Legg-Calve-Perthes Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lipoma	Lipoma	BEFREE	31640774		★☆☆☆☆ Found in Text Mining only
Lipomatosis, Multiple	Lipomatosis	BEFREE	31640774		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28100410, 30231922, 30999932		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	28100410		★☆☆☆☆ Found in Text Mining only
Localized scleroderma	Scleroderma	BEFREE	23507196		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	20511364, 27065333, 29228690, 30231922, 30502484, 31737569		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	12678339		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	29228690, 29530484, 31413818		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28345259, 30502484, 30999932		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	29560517, 30502262, 30995524, 31617091		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	15367707, 21720807, 24756834, 2478022, 9788574		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	30021673		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	30664617		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	17347910		★☆☆☆☆ Found in Text Mining only
Micromelia	Micromelia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mucopolysaccharidosis IV	Mucopolysaccharidosis	BEFREE	17579668, 20819661		★☆☆☆☆ Found in Text Mining only
Multiple Epiphyseal Dysplasia	Multiple Epiphyseal Dysplasia	BEFREE	10364514, 10405447, 10655510, 11084047, 11200990, 11479597, 11501943, 11528506, 11565064, 11782471, 11891674, 11968079, 12479386, 12483304, 12483437, 12768438, 12792737, 12819015, 15183431, 15266613, 15337766, 15503005, 15694129, 15756302, 15880723, 16440132, 16514635, 17133256, 17200202, 17570134, 18193163, 18682400, 20578249, 20830670, 20936634, 21834907, 21922596, 21965141, 23506586, 24595329, 24997222, 28685811, 29530484, 30541462, 7670472, 9184241, 9463320, 9921895, 9923655		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple epiphyseal dysplasia type 1	Multiple Epiphyseal Dysplasia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple epiphyseal dysplasia type 1	Multiple Epiphyseal Dysplasia	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Myocardial Infarction	Myocardial Infarction	BEFREE	28429960		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	27065333, 28938620, 29228690, 29560517, 30231922, 30502484, 31617091		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	21868677		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	31746390	Associate	★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29549054, 30100245		★☆☆☆☆ Found in Text Mining only
Oral Submucous Fibrosis	Oral Submucous Fibrosis	BEFREE	18768491		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	16542502, 16802351, 18291686, 18485748, 20187133, 20305824, 22561860, 29741735, 30903650, 31696983, 33787363, 34680093	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis	Osteoarthritis	Pubtator	9920012	Stimulate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis Hip	Osteoarthritis	Pubtator	22179616, 31352363	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis Knee	Osteoarthritis	Pubtator	26848781	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis of hip	Osteoarthritis Of Hip	BEFREE	25057126, 28319091, 30388026, 30391538		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis of hip	Osteoarthritis Of Hip	CTD_human_DG	28319091		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis of hip	Osteoarthritis Of Hip	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis, Knee	Knee osteoarthritis	LHGDN	19035482		★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	BEFREE	27546883, 28261974, 28910372, 29351749, 29673544, 30317002, 30340615, 30526057, 31665048, 31696983		★☆☆☆☆ Found in Text Mining only
Osteoarthrosis Deformans	Osteoarthrosis Deformans	CTD_human_DG	7670472		★☆☆☆☆ Found in Text Mining only
Osteochondrodysplasias	Osteochondrodysplasias	Pubtator	10364514, 10465113, 10655510, 10852928, 11084047, 11565064, 11782471, 15183431, 16514635, 17133256, 20936634, 21843649, 21922596, 24595329, 33030144, 34680093, 39596690, 9388247, 9463320, 9756911	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteochondrodysplasias	Osteochondrodysplasia	LHGDN	11891674, 12768438		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteochondrodysplasias	Osteochondrodysplasia	BEFREE	17579668, 20819661, 31177591		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoporosis	Osteoporosis	BEFREE	29067460		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	24101134		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	12678339		★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	31072097		★☆☆☆☆ Found in Text Mining only
Pancreatitis, Chronic	Pancreatitis	BEFREE	12678339		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	29228690, 31413818		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	23716368, 36124532	Associate	★☆☆☆☆ Found in Text Mining only
Pseudoachondroplasia	Pseudoachondroplasia	BEFREE	10405447, 10753957, 11084047, 11691584, 11745002, 11746044, 11746045, 11782471, 11891674, 11968079, 12479386, 12483304, 12483437, 12768438, 12792737, 12819015, 14580238, 15094116, 15183431, 15266613, 15337766, 15551305, 15579310, 15694129, 15756302, 15880723, 16199550, 16514635, 16520029, 17200202, 17307347, 17394206, 17570134, 17579668, 18193163, 18546327, 19762713, 20578249, 20819661, 20830670, 20936634, 21042783, 21599986, 21644213, 21922596, 23562786, 24194321, 24595329, 24892720, 24997222, 27299778, 27432013, 28162960, 28685811, 28924040, 29104872, 29309831, 29530484, 30553437, 31177591, 7670471, 7670472, 9021009, 9184241, 9188668, 9388247, 9463320, 9632164, 9749943, 9880218, 9887340, 9921895, 9923655		★☆☆☆☆ Found in Text Mining only
Pseudoachondroplasia	Pseudoachondroplasia	UNIPROT_DG	10852928, 11084047, 11746044, 11746045, 21922596, 7670471, 7670472, 9184241, 9452026, 9452063, 9463320, 9921895		★☆☆☆☆ Found in Text Mining only
Pseudoachondroplasia	Pseudoachondroplasia	Orphanet			★☆☆☆☆ Found in Text Mining only
Pseudoachondroplasia	Pseudoachondroplasia	CTD_human_DG	7670471, 7670472, 9887340		★☆☆☆☆ Found in Text Mining only
Pseudoachondroplasia	Pseudoachondroplasia	GENOMICS_ENGLAND_DG	9021009		★☆☆☆☆ Found in Text Mining only
Pseudoachondroplasia	Pseudoachondroplasia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
PSEUDOACHONDROPLASIA, SEVERE	Pseudoachondroplasia	BEFREE	11746044		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PSEUDOACHONDROPLASIA, SEVERE	Pseudoachondroplasia	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Respiratory Failure	Respiratory Failure	BEFREE	19217887		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	10376735, 11238672, 18576344, 28373131, 28473207, 28889184, 29105312, 9291852, 9714346		★☆☆☆☆ Found in Text Mining only
Sarcoma	Sarcoma	BEFREE	20212452		★☆☆☆☆ Found in Text Mining only
Scleroderma	Scleroderma	BEFREE	16520029		★☆☆☆☆ Found in Text Mining only
Scleroderma Systemic	Systemic sclerosis	Pubtator	24330664	Stimulate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensory neuropathy	Sensory neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	7626385		★☆☆☆☆ Found in Text Mining only
Skeletal dysplasia	Skeletal Dysplasia	BEFREE	31177591		★☆☆☆☆ Found in Text Mining only
Skin Erosion	Skin Erosion	BEFREE	15183431, 29437628		★☆☆☆☆ Found in Text Mining only
Spinal Muscular Atrophy	Spinal Muscular Atrophy	BEFREE	30188931		★☆☆☆☆ Found in Text Mining only
Spondyloepimetaphyseal disorder	Spondyloepimetaphyseal dysplasia	BEFREE	9258750		★☆☆☆☆ Found in Text Mining only
Spondyloepiphyseal dysplasia, congenita	Spondyloepiphyseal dysplasia congenita	BEFREE	11746045		★☆☆☆☆ Found in Text Mining only
Synovitis	Synovitis	BEFREE	29549054		★☆☆☆☆ Found in Text Mining only
Systemic Scleroderma	Scleroderma	BEFREE	16520029, 18408251		★☆☆☆☆ Found in Text Mining only
Teratozoospermia	Teratozoospermia	BEFREE	16362321		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	37229458	Stimulate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	28938620		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	33910854	Associate	★☆☆☆☆ Found in Text Mining only
Vascular Diseases	Vascular Diseases	BEFREE	28849199		★☆☆☆☆ Found in Text Mining only