MATN1

Summary

MATN1 (matrilin 1, HGNC:6907) is a protein-coding gene on chromosome 1p35.2, encoding Matrilin-1 (P21941). A major component of the extracellular matrix of non-articular cartilage.

This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. Mutations of this gene have been associated with variety of inherited chondrodysplasias.

Source: NCBI Gene 4146 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_002379

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6907
Approved symbol	MATN1
Name	matrilin 1
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162510
Ensembl biotype	protein_coding
OMIM	115437
Entrez	4146

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000373765, ENST00000477320, ENST00000494561

RefSeq mRNA: 1 — MANE Select: NM_002379 NM_002379

CCDS: CCDS336

Canonical transcript exons

ENST00000373765 — 8 exons

Exon	Start	End
ENSE00001065934	30715909	30716325
ENSE00001150947	30714247	30714327
ENSE00001174040	30718735	30718957
ENSE00001174044	30721405	30721751
ENSE00001461490	30711277	30713631
ENSE00001627704	30723458	30723585
ENSE00003588852	30715157	30715309
ENSE00003677703	30716790	30716915

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 96.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1055 / max 97.7124, expressed in 12 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11385	0.1055	12

Top tissues by expression

259 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	96.56	gold quality
tibia	UBERON:0000979	92.06	gold quality
trachea	UBERON:0003126	83.37	gold quality
tendon of biceps brachii	UBERON:0008188	76.52	gold quality
pancreatic ductal cell	CL:0002079	74.88	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.11	silver quality
oocyte	CL:0000023	71.95	gold quality
cervix squamous epithelium	UBERON:0006922	70.71	gold quality
olfactory bulb	UBERON:0002264	69.89	gold quality
type B pancreatic cell	CL:0000169	69.80	gold quality
secondary oocyte	CL:0000655	69.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	69.67	gold quality
diaphragm	UBERON:0001103	67.23	gold quality
hair follicle	UBERON:0002073	67.06	gold quality
male germ cell	CL:0000015	67.02	gold quality
medial globus pallidus	UBERON:0002477	66.65	silver quality
sperm	CL:0000019	66.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.84	gold quality
globus pallidus	UBERON:0001875	65.32	silver quality
vena cava	UBERON:0004087	63.99	gold quality
orbitofrontal cortex	UBERON:0004167	63.90	gold quality
mucosa of urinary bladder	UBERON:0001259	63.70	gold quality
gingival epithelium	UBERON:0001949	63.66	gold quality
squamous epithelium	UBERON:0006914	63.34	gold quality
saphenous vein	UBERON:0007318	63.11	gold quality
granulocyte	CL:0000094	62.96	gold quality
pericardium	UBERON:0002407	62.75	gold quality
oviduct epithelium	UBERON:0004804	62.48	gold quality
tongue squamous epithelium	UBERON:0006919	62.46	gold quality
thymus	UBERON:0002370	62.10	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HBP1, NFIC, SOX17, SOX5, SOX6, SOX9

miRNA regulators (miRDB)

69 targeting MATN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145

Literature-anchored findings (GeneRIF, showing 14)

• Pseudoachondroplasia is associated with mutations in the cartilage oligomatrix protein gene. (PMID:15552564)
• the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in adolescent idiopathic scoliosis . (PMID:18985072)
• The tagSNP rs1149048 polymorphism in the MATN1 promoter region is associated with both susceptibility and disease severity in adolescent idiopathic scoliosis. (PMID:20092731)
• There is an association between matrilin-1 levels and curve progression in adolescent idiopathic scoliosis. (PMID:20137399)
• Genotype GG of matrilin-1 gene is indicative of less bracing effectiveness in adolescent idiopathic scoliosis. (PMID:20137728)
• Matrilin-1 A-domains have a role in cartilage ECM assembly (PMID:20729554)
• Genotyping results showed Matrilin-1 polymorphism haplotype TGC (ht4; 158T, 7987G, and 8572C alleles) had pronounced risk effect for mandibular prognathism compared with controls. (PMID:20739701)
• we concluded that MATN1 SNP is not associated with either adolescent idiopathic scoliosis predisposition or curve severity in Japanese. (PMID:21308753)
• The A allele of single nucleotide polymorphism rs1065755 in the MATN1 gene is associated with adolescent idiopathic scoliosis. (PMID:22193623)
• no significant difference in single nucleotide polymorphism between adolescent idiopathic scoliosis cases and controls (PMID:22278929)
• this meta-analysis found an overall significant association of rs1149048 polymorphism with risk of AIS, especially in Asian population. (PMID:24469715)
• Matrilin-1 is an inhibitor of neovascularization (PMID:24692560)
• polymorphisms associated with mandibular retrognathism (PMID:29407503)
• We identified two candidate mutations in COL1A2 and MATN1, which might be affected by the main known mutation in B3GALT6. Our finding replicated a previously identified mutation in KIF22 to be potentially associated with spondyloepimetaphyseal dysplasia with joint laxity. We also show that our identified candidate mutation genes, COL1A2, MATN1 and KIF22, are in a direct biological interaction with B3GALT6. (PMID:30358852)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	matn1	ENSDARG00000030215
mus_musculus	Matn1	ENSMUSG00000040533
rattus_norvegicus	Matn1	ENSRNOG00000010932

Paralogs (12): COCH (ENSG00000100473), COL12A1 (ENSG00000111799), MATN4 (ENSG00000124159), MATN3 (ENSG00000132031), MATN2 (ENSG00000132561), COL6A3 (ENSG00000163359), VWA2 (ENSG00000165816), COL6A5 (ENSG00000172752), VWA1 (ENSG00000179403), COL14A1 (ENSG00000187955), VIT (ENSG00000205221), COL6A6 (ENSG00000206384)

Protein

Protein identifiers

Matrilin-1 — P21941 (reviewed: P21941)

Alternative names: Cartilage matrix protein

All UniProt accessions (1): P21941

UniProt curated annotations — full annotation on UniProt →

Function. A major component of the extracellular matrix of non-articular cartilage. Binds to type 2 collagens and forms long concatenated protein networks as part of the extracellular matrix. Required for the network-like organization and bundling of collagen fibrils surrounding chondrocytes in the zones of maturation and hypertrophy. Required for mechanotransduction and adaption to mechanical loading in cartilage chondrocytes, resulting in an increase in expression of the extracellular matrix components ACAN and COL2A1. Acts as a moderator of angiogenesis in response to injury.

Subunit / interactions. Homotrimer. Part of a complex composed of MATN1 (via VWFA1 domain), type 2 collagens and type 6 collagens. Forms a complex (via covalent bonds) with ACAN; the interaction increases in abundance with increasing age of the organism via an increase in occupancy of MATN1 binding sites. Interacts with COMP.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. N-glycosylated; reduces binding affinity for type 2 collagens.

RefSeq proteins (1): NP_002370* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002035	VWF_A	Domain
IPR019466	Matrilin_CC_trimer	Domain
IPR036337	Matrilin_CC_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR050525	ECM_Assembly_Org	Family

Pfam: PF00092, PF10393, PF14670

UniProt features (14 total): disulfide bond 3, domain 3, mutagenesis site 2, glycosylation site 2, signal peptide 1, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21941-F1	83.72	0.50

Functional residue map

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

Disulfide bonds (3): 249–262, 227–238, 234–247

Glycosylation sites (2): 76, 344

Mutagenesis-validated functional residues (2):

Position	Phenotype
76	abolishes n-glycosylation; no effect on protein secretion and increases interaction with type 2 collagens.
344	abolishes n-glycosylation; no effect on protein secretion and increases interaction with type 2 collagens.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3000178	ECM proteoglycans
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 120 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, FISCHER_G1_S_CELL_CYCLE, GOBP_GROWTH, RACCACAR_AML_Q6, GOBP_CHONDROCYTE_DEVELOPMENT, GGGTGGRR_PAX4_03, GOBP_CARTILAGE_MORPHOGENESIS, GOBP_BONE_GROWTH, CAGCTG_AP4_Q5, SHIPP_DLBCL_CURED_VS_FATAL_DN, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, GOBP_BONE_MINERALIZATION

GO Biological Process (5): growth plate cartilage chondrocyte morphogenesis (GO:0003429), extracellular matrix organization (GO:0030198), regulation of bone mineralization (GO:0030500), protein-containing complex assembly (GO:0065003), chondrocyte differentiation (GO:0002062)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), extracellular matrix (GO:0031012), matrilin complex (GO:0120216)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
growth plate cartilage chondrocyte differentiation	1
growth plate cartilage morphogenesis	1
chondrocyte morphogenesis	1
extracellular structure organization	1
external encapsulating structure organization	1
regulation of ossification	1
bone mineralization	1
regulation of biomineral tissue development	1
cellular component assembly	1
protein-containing complex organization	1
cell differentiation	1
cartilage development	1
structural molecule activity	1
extracellular matrix	1
metal ion binding	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1
non-collagenous component of interstitial matrix	1
extracellular protein-containing complex	1

Protein interactions and networks

STRING

933 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MATN1	ACAN	P16112	751
MATN1	COL2A1	P02458	705
MATN1	SOX9	P48436	643
MATN1	CHAD	O15335	575
MATN1	MIA	Q16674	570
MATN1	DCN	P07585	553
MATN1	BGN	P13247	548
MATN1	PRKG2	Q13237	527
MATN1	MYO1H	Q8N1T3	509
MATN1	HAPLN1	P10915	507
MATN1	COMP	P49747	505
MATN1	PTHLH	P12272	485
MATN1	COL9A3	Q14050	481
MATN1	COL9A1	P20849	479
MATN1	COL1A1	P02452	467

IntAct

9 interactions, top by confidence:

A	B	Type	Score
COL2A1	MATN1	psi-mi:“MI:0407”(direct interaction)	0.560
COL9A1	MATN1	psi-mi:“MI:0407”(direct interaction)	0.440
MATN1	H2BC14	psi-mi:“MI:0915”(physical association)	0.400
MATN4	MATN1	psi-mi:“MI:0914”(association)	0.350
MATN4	HSPA5	psi-mi:“MI:0914”(association)	0.350
MATN1	POR	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): MATN1 (Affinity Capture-MS), HIST1H2BM (Proximity Label-MS), GHITM (Affinity Capture-MS), POR (Affinity Capture-MS), STIM1 (Affinity Capture-MS), MATN1 (Affinity Capture-MS), MATN1 (Reconstituted Complex), MATN2 (Reconstituted Complex), MATN3 (Reconstituted Complex), MATN4 (Reconstituted Complex)

ESM2 similar proteins: A2AX52, A6H584, A6NMZ7, A6X935, A8TX70, E1BMV3, E7FF10, O00339, O02668, O08746, O55123, O89029, P05099, P06681, P12111, P15989, P19823, P19827, P21180, P21941, P51942, P79263, P97278, P97279, Q0IIH7, Q0V8T0, Q0V8T5, Q0V8T6, Q0V8T7, Q0VCM5, Q14624, Q21540, Q29052, Q3SYW2, Q3T052, Q5GFL6, Q61702, Q61703, Q6DCQ6, Q70UZ7

Diamond homologs: A2AX52, A6QLN9, E1BMV3, E7FF10, O00339, O08746, O15232, O35701, O42163, O42401, O43405, O75578, O89029, O95460, P05099, P12111, P13944, P15989, P17301, P18614, P21941, P24063, P32018, P51942, P53710, P56199, P84552, Q02388, Q21540, Q3V3R4, Q5EA64, Q5GFL6, Q60847, Q62507, Q63870, Q642A6, Q6DCQ6, Q6PCB0, Q6UXI7, Q70UZ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1499 predictions. Top by Δscore:

Variant	Effect	Δscore
1:30715185:G:A	donor_gain	1.0000
1:30716272:C:CT	acceptor_gain	1.0000
1:30716272:C:T	acceptor_gain	1.0000
1:30716322:CAGA:C	acceptor_gain	1.0000
1:30716326:C:CC	acceptor_gain	1.0000
1:30716911:CACCA:C	acceptor_gain	1.0000
1:30716913:CCA:C	acceptor_gain	1.0000
1:30716914:CA:C	acceptor_gain	1.0000
1:30716914:CAC:C	acceptor_gain	1.0000
1:30716915:AC:A	acceptor_loss	1.0000
1:30716916:C:CC	acceptor_gain	1.0000
1:30716916:CTG:C	acceptor_loss	1.0000
1:30718746:T:TA	donor_gain	1.0000
1:30718756:T:TA	donor_gain	1.0000
1:30718757:C:A	donor_gain	1.0000
1:30721400:CGTA:C	donor_loss	1.0000
1:30721401:GTAC:G	donor_loss	1.0000
1:30721402:TACC:T	donor_loss	1.0000
1:30721404:C:CG	donor_loss	1.0000
1:30721404:CCTTG:C	donor_gain	1.0000
1:30714250:T:A	donor_gain	0.9900
1:30714328:C:CC	acceptor_gain	0.9900
1:30715151:A:AC	donor_gain	0.9900
1:30715151:ACTC:A	donor_loss	0.9900
1:30715152:C:CC	donor_gain	0.9900
1:30715153:TCA:T	donor_loss	0.9900
1:30715154:C:CC	donor_loss	0.9900
1:30715155:A:AC	donor_gain	0.9900
1:30715155:AC:A	donor_gain	0.9900
1:30715156:C:CC	donor_gain	0.9900

AlphaMissense

3247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:30715249:G:T	A423D	1.000
1:30715261:A:G	L419P	1.000
1:30715294:G:T	A408D	1.000
1:30715971:A:T	V382D	1.000
1:30716043:A:G	L358P	1.000
1:30716169:A:G	L316P	1.000
1:30715250:C:G	A423P	0.999
1:30715252:A:C	I422R	0.999
1:30715252:A:T	I422K	0.999
1:30715288:C:T	G410D	0.999
1:30715952:G:C	S388R	0.999
1:30715952:G:T	S388R	0.999
1:30715954:T:G	S388R	0.999
1:30715959:C:T	G386D	0.999
1:30715960:C:A	G386C	0.999
1:30716043:A:T	L358H	0.999
1:30716046:G:T	A357D	0.999
1:30716158:A:G	S320P	0.999
1:30716173:C:A	G315W	0.999
1:30716268:G:A	S283F	0.999
1:30716268:G:T	S283Y	0.999
1:30716269:A:G	S283P	0.999
1:30716274:T:A	D281V	0.999
1:30716280:A:G	L279P	0.999
1:30716283:A:G	F278S	0.999
1:30716289:A:G	L276P	0.999
1:30715289:C:G	G410R	0.998
1:30715291:A:T	V409E	0.998
1:30715948:C:G	D390H	0.998
1:30715961:A:C	D385E	0.998

dbSNP variants (sampled 300 via entrez): RS1000109348 (1:30720489 G>C), RS1000258559 (1:30715747 T>C), RS1000978765 (1:30719249 C>G,T), RS1001180956 (1:30717542 G>A), RS1001262870 (1:30717247 A>T), RS1001285891 (1:30725157 T>C), RS1001322631 (1:30720753 T>C), RS1001333918 (1:30721118 A>G), RS1001419462 (1:30711485 A>G), RS1001701005 (1:30722683 G>A,T), RS1001870433 (1:30711774 C>G,T), RS1002474877 (1:30712760 G>A), RS1003002702 (1:30722090 A>T), RS1003328163 (1:30723302 T>C), RS1003337998 (1:30723543 G>A)

Disease associations

OMIM: gene MIM:115437 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003391_1	Low high density lipoprotein cholesterol levels	3.000000e-09
GCST004946_45	Schizophrenia	3.000000e-10
GCST005352_30	Paclitaxel disposition in epithelial ovarian cancer	4.000000e-06
GCST007201_246	Schizophrenia	1.000000e-09
GCST007201_46	Schizophrenia	6.000000e-11
GCST007257_1	Broad depression or schizophrenia	2.000000e-08
GCST011353_34	Serum alkaline phosphatase levels	3.000000e-11
GCST90002393_121	Monocyte count	8.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
tebuconazole	decreases expression	1
monoisoamyl-2,3-dimercaptosuccinate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenates	affects cotreatment, increases expression	1
Atrazine	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.