MATN3 (matrilin 3)

Gene

• Entrez ID: 4148
• Gene name: Matrilin 3
• Gene symbol: MATN3
• Synonyms (NCBI Gene): DIPOA, EDM5, HOA, OADIP, OS2, SEMDBCD
• Chromosome: 2
• Chromosome location: 2p24.1
• Summary: This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins is thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This protein contains two

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28939677	G>T	Pathogenic	Coding sequence variant, missense variant
rs104893637	G>A	Pathogenic	Coding sequence variant, missense variant
rs104893640	C>T	Pathogenic	Coding sequence variant, missense variant
rs104893641	C>G	Pathogenic	Coding sequence variant, missense variant
rs104893645	A>T	Pathogenic	Coding sequence variant, missense variant
rs201755444	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs397515546	G>A	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019479	hsa-miR-148b-3p	Microarray	17612493
MIRT030037	hsa-miR-26b-5p	Microarray	19088304
MIRT1133736	hsa-miR-186	CLIP-seq
MIRT1133737	hsa-miR-3133	CLIP-seq
MIRT1133738	hsa-miR-633	CLIP-seq
MIRT2038082	hsa-miR-128	CLIP-seq
MIRT2038083	hsa-miR-27a	CLIP-seq
MIRT2038084	hsa-miR-27b	CLIP-seq
MIRT2038085	hsa-miR-374c	CLIP-seq
MIRT2038086	hsa-miR-3924	CLIP-seq
MIRT2038087	hsa-miR-4272	CLIP-seq
MIRT2038088	hsa-miR-4712-5p	CLIP-seq
MIRT2038089	hsa-miR-4797-3p	CLIP-seq
MIRT2038090	hsa-miR-513a-5p	CLIP-seq
MIRT2038091	hsa-miR-655	CLIP-seq
MIRT2038092	hsa-miR-770-5p	CLIP-seq
MIRT2268013	hsa-miR-340	CLIP-seq
MIRT2567699	hsa-miR-3165	CLIP-seq
MIRT2567700	hsa-miR-34c-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	IEA
GO:0001501	Process	Skeletal system development	TAS	9350998
GO:0005201	Function	Extracellular matrix structural constituent	TAS	9350998
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	15075323, 16287128, 23956175, 25416956, 32296183
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0030198	Process	Extracellular matrix organization	IEA
GO:0030198	Process	Extracellular matrix organization	ISO
GO:0030198	Process	Extracellular matrix organization	NAS	10660556
GO:0031012	Component	Extracellular matrix	IBA
GO:0031012	Component	Extracellular matrix	IEA
GO:0031012	Component	Extracellular matrix	TAS	9350998
GO:0051216	Process	Cartilage development	IEA
GO:0120216	Component	Matrilin complex	IEA
GO:0120216	Component	Matrilin complex	ISO

Other IDs

• MIM: 602109
• HGNC: 6909
• e!Ensembl: ENSG00000132031

Protein

• UniProt ID: O15232
• Protein name: Matrilin-3
• Protein function: Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00092	VWA	83 → 257	von Willebrand factor type A domain	Domain
  PF14670	FXa_inhibition	310 → 346		Domain
  PF14670	FXa_inhibition	352 → 388		Domain
  PF10393	Matrilin_ccoil	439 → 483	Trimeric coiled-coil oligomerisation domain of matrilin	Coiled-coil

• Tissue specificity: TISSUE SPECIFICITY: Expressed only in cartilaginous tissues, such as vertebrae, ribs and shoulders.
• Sequence:

  MPRPAPARRLPGLLLLLWPLLLLPSAAPDPVARPGFRRLETRGPGGSPGRRPSPAAPDGA
  PASGTSEPGRARGAGVCKSRPLDLVFIIDSSRSVRPLEFTKVKTFVSRIIDTLDIGPADT
  RVAVVNYASTVKIEFQLQAYTDKQSLKQAVGRITPLSTGTMSGLAIQTAMDEAFTVEAGA
  REPSSNIPKVAIIVTDGRPQDQVNEVAARAQASGIELYAVGVDRADMASLKMMASEPLEE
  HVFYVETYGVIEKLSSRFQETFCALDPCVLGTHQCQHVCISDGEGKHHCECSQGYTLNAD
  KKTCSALDRCALNTHGCEHICVNDRSGSYHCECYEGYTLNEDRKTCSAQDKCALGTHGCQ
  HICVNDRTGSHHCECYEGYTLNADKKTCSVRDKCALGSHGCQHICVSDGAASYHCDCYPG
  YTLNEDKKTCSATEEARRLVSTEDACGCEATLAFQDKVSSYLQRLNTKLDDILEKLKINE
  YGQIHR

• Sequence length: 486

Pathways

Reactome:

ECM proteoglycans
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Post-translational protein phosphorylation

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
Multiple epiphyseal dysplasia	Likely pathogenic; Pathogenic	rs2103484088, rs104893645, rs104893637, rs28939677, rs397515546	RCV002210945 RCV002054422 RCV002054423 RCV002054424 RCV002054898	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple epiphyseal dysplasia type 5	Likely pathogenic; Pathogenic	rs1673102663, rs104893645, rs104893637, rs28939677, rs104893641, rs397515546	RCV002238723 RCV000007976 RCV000007977 RCV000007979 RCV000007982 RCV000055878	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Osteoarthritis susceptibility 2	Likely pathogenic	rs749515743	RCV001198723	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spondyloepimetaphyseal dysplasia, matrilin-3 type	Likely pathogenic; Pathogenic	rs104893637, rs104893639, rs397515546	RCV004566694 RCV000055879 RCV001375669	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ 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; Benign; Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPIPHYSEAL DYSPLASIA, MULTIPLE, 5	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MATN3-related disorder	Likely benign; Benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple Epiphyseal Dysplasia, Dominant	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOCHONDRODYSPLASIAS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPONDYLOEPIMETAPHYSEAL DYSPLASIA, BOROCHOWITZ-CORMIER-DAIRE TYPE	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPONDYLOEPIMETAPHYSEAL DYSPLASIA, MATRILIN-3 RELATED	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthropathy	Arthropathy	BEFREE	27533128		★☆☆☆☆ Found in Text Mining only
Bone Diseases	Bone Disease	BEFREE	17881354		★☆☆☆☆ Found in Text Mining only
Bone Diseases	Bone disease	Pubtator	17881354	Associate	★☆☆☆☆ Found in Text Mining only
Cartilage Diseases	Cartilage disease	Pubtator	18759284, 29483929	Associate	★☆☆☆☆ Found in Text Mining only
Chondroma	Chordoma	Pubtator	18759284	Stimulate	★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	BEFREE	18759284		★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	Pubtator	18759284	Associate	★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	11950247, 16396979, 17881354, 18759284, 19840795, 20077500, 20971668, 28139355, 28846474, 29483929, 30001809		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	LHGDN	12736871		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Enchondroma	Enchondroma	BEFREE	18759284		★☆☆☆☆ Found in Text Mining only
Epiphyseal dysplasia	Epiphyseal dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epiphyseal dysplasia multiple 1	Epiphyseal dysplasia	Pubtator	29483929	Associate	★☆☆☆☆ Found in Text Mining only
EPIPHYSEAL DYSPLASIA, MULTIPLE, 5	Epiphyseal dysplasia	UNIPROT_DG	11479597, 12884427, 14729835, 15459972, 15948199, 16287128, 21922596		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPIPHYSEAL DYSPLASIA, MULTIPLE, 5	Epiphyseal dysplasia	GENOMICS_ENGLAND_DG	14729835, 16287128, 20358595		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPIPHYSEAL DYSPLASIA, MULTIPLE, 5	Epiphyseal dysplasia	BEFREE	31260448		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPIPHYSEAL DYSPLASIA, MULTIPLE, 5	Epiphyseal dysplasia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPIPHYSEAL DYSPLASIA, MULTIPLE, 5	Epiphyseal dysplasia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fuchs' Endothelial Dystrophy	Fuchs endothelial dystrophy	Pubtator	35239706	Associate	★☆☆☆☆ Found in Text Mining only
Gastric Adenocarcinoma	Gastric Cancer	BEFREE	29343680		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	17881354, 39293509	Associate	★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	16396979		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	16396979, 32495856	Associate	★☆☆☆☆ Found in Text Mining only
Jeune thoracic dystrophy	Jeune Thoracic Dystrophy	BEFREE	30080953		★☆☆☆☆ Found in Text Mining only
Micromelia	Micromelia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Motor Neuron Disease	Motor neuron disease	Pubtator	39293509	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Epiphyseal Dysplasia	Multiple Epiphyseal Dysplasia	BEFREE	11479597, 11891674, 12884427, 14994237, 15459972, 15503005, 16287128, 17881354, 18205203, 21922596, 21965141, 23956175, 26499313, 30080953, 31260448		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple Epiphyseal Dysplasia	Multiple Epiphyseal Dysplasia	GENOMICS_ENGLAND_DG	16287128, 20358595		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple Epiphyseal Dysplasia	Multiple Epiphyseal Dysplasia	HPO_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple epiphyseal dysplasia type 5	Multiple Epiphyseal Dysplasia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Multiple epiphyseal dysplasia type 5	Multiple Epiphyseal Dysplasia	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neoplasms	Neoplasms	BEFREE	18759284, 28576067, 3304817		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	11950247, 12736871, 16396979, 17881354, 18759284, 22973175, 24716474, 29483929, 33166667	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis	Osteoarthritis	Pubtator	19840795, 30307059	Stimulate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoarthritis Knee	Osteoarthritis	Pubtator	22973175	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthrosis Deformans	Osteoarthrosis Deformans	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Osteoarthrosis of the carpometacarpal joint of the thumb	Osteoarthrosis Of Joints Of Thumb	BEFREE	16396979		★☆☆☆☆ Found in Text Mining only
Osteochondrodysplasias	Osteochondrodysplasias	Pubtator	11565064, 17881354, 21922596, 24629099, 30740902, 32264862, 39293509	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteochondrodysplasias	Osteochondrodysplasia	LHGDN	14729835, 14994237, 15459972, 16287128		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosarcoma	Osteosarcoma	Pubtator	33308057	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	29571090		★☆☆☆☆ Found in Text Mining only
Periostitis	Periostitis	BEFREE	3304817		★☆☆☆☆ Found in Text Mining only
Premature osteoarthritis	Premature osteoarthritis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pseudoachondroplasia	Pseudoachondroplasia	BEFREE	15694129, 18193163, 21922596		★☆☆☆☆ Found in Text Mining only
Pterygium	Pterygium	BEFREE	28501948		★☆☆☆☆ Found in Text Mining only
Regular astigmatism - corneal	Corneal astigmatism	BEFREE	28501948		★☆☆☆☆ Found in Text Mining only
Spondyloepimetaphyseal disorder	Spondyloepimetaphyseal dysplasia	BEFREE	23956136, 26499313		★☆☆☆☆ Found in Text Mining only
Spondyloepimetaphyseal disorder	Spondyloepimetaphyseal dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spondyloepimetaphyseal Dysplasia, Matrilin-3 Related	Spondyloenchondrodysplasia	UNIPROT_DG	15121775		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spondyloepimetaphyseal Dysplasia, Matrilin-3 Related	Spondyloenchondrodysplasia	ORPHANET_DG	15121775		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spondyloepimetaphyseal Dysplasia, Matrilin-3 Related	Spondyloenchondrodysplasia	GENOMICS_ENGLAND_DG	16287128		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spondyloepimetaphyseal Dysplasia, Matrilin-3 Related	Spondyloenchondrodysplasia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spondyloepimetaphyseal dysplasia, matrilin-3 type	Spondyloepiphyseal dysplasia	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Stomach Neoplasms	Stomach neoplasms	Pubtator	34281542, 34746312	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	34900024	Stimulate	★☆☆☆☆ Found in Text Mining only
Thoracic hypoplasia	Thoracic hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only