MATN3

matrilin 3, the group of Matrilins

Basic information

Region (hg38): 2:19992052-20012668

Links

ENSG00000132031 ∙ NCBI:4148 ∙ OMIM:602109 ∙ HGNC:6909 ∙ Uniprot:O15232 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple epiphyseal dysplasia type 5 (Definitive), mode of inheritance: AD
• multiple epiphyseal dysplasia type 5 (Supportive), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia, matrilin-3 type (Supportive), mode of inheritance: AR
• multiple epiphyseal dysplasia type 5 (Strong), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia, matrilin-3 type (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epiphyseal dysplasia, multiple, 5; Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	13849708; 11479597; 11528506; 12884427; 15121775; 14729835; 15948199; 18205203; 20301302; 21922596; 21965141

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MATN3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MATN3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	39	5	50
missense		4	120	10	4	138
nonsense			3			3
start loss						0
frameshift			8			8
inframe indel		1				1
splice donor/acceptor (+/-2bp)			3			3
splice region			5	3		8
non coding		1	10	11	18	40
Total	0	6	150	60	27

Variants in MATN3

This is a list of pathogenic ClinVar variants found in the MATN3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-19992067-T-G		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 12, 2018)
2-19992115-T-C		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 13, 2018)
2-19992122-G-C		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 12, 2018)
2-19992156-C-T		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 13, 2018)
2-19992352-G-A		Multiple epiphyseal dysplasia type 5	Benign (Jan 12, 2018)
2-19992362-A-C		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 13, 2018)
2-19992451-C-T		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 12, 2018)
2-19992799-A-T		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 12, 2018)
2-19992900-T-G		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 12, 2018)
2-19992935-G-A		Cranioectodermal dysplasia • Multiple Epiphyseal Dysplasia, Dominant • Short rib-polydactyly syndrome • Multiple epiphyseal dysplasia type 5	Benign (Nov 12, 2018)
2-19992959-T-A		Multiple epiphyseal dysplasia type 5	Uncertain significance (Apr 27, 2017)
2-19993037-C-T		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 13, 2018)
2-19993067-G-C		Multiple epiphyseal dysplasia type 5	Uncertain significance (Jan 12, 2018)
2-19993116-G-A		Inborn genetic diseases	Uncertain significance (Jun 04, 2024)
2-19993133-T-A			Uncertain significance (May 08, 2019)
2-19993160-T-G			Likely benign (Oct 16, 2022)
2-19993170-G-A		not specified • Cranioectodermal dysplasia • Multiple Epiphyseal Dysplasia, Dominant • Short rib-polydactyly syndrome • Multiple epiphyseal dysplasia type 5	Benign/Likely benign (Jan 31, 2024)
2-19993173-AGTT-A			Likely benign (Aug 23, 2023)
2-19993174-G-A		Multiple epiphyseal dysplasia type 5	Uncertain significance (Mar 30, 2018)
2-19994065-A-G			Benign (May 13, 2021)
2-19994275-G-C		not specified	Benign (Nov 12, 2018)
2-19994286-C-T			Likely benign (Jan 12, 2024)
2-19994297-A-G			Uncertain significance (Dec 09, 2022)
2-19994310-A-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
2-19994324-C-T			Benign (Oct 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MATN3	protein_coding	protein_coding	ENST00000407540	8	20584

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.35e-8	0.366	124599	0	47	124646	0.000189

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.771	201	234	0.858	0.0000129	3125
Missense in Polyphen		84	106.12	0.79156		1237
Synonymous	1.10	76	89.2	0.852	0.00000509	986
Loss of Function	0.779	14	17.5	0.799	9.63e-7	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000640	0.000633
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000169	0.000168
Middle Eastern	0.00	0.00
South Asian	0.000534	0.000523
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.
• Disease: DISEASE: Spondyloepimetaphyseal dysplasia MATN3-related (SEMD- MATN3) [MIM:608728]: A bone disease characterized by disproportionate early-onset dwarfism, bowing of the lower limbs, lumbar lordosis and normal hands. Skeletal abnormalities include short, wide and stocky long bones with severe epiphyseal and metaphyseal changes, hypoplastic iliac bones and flat, ovoid vertebral bodies. {ECO:0000269|PubMed:15121775}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Osteoarthritis 2 (OS2) [MIM:140600]: A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. In the hand, osteoarthritis can develop in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints. Patients with osteoarthritis may have one, a few, or all of these sites affected. {ECO:0000269|PubMed:12736871}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);ECM proteoglycans (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.46

Haploinsufficiency Scores

• pHI: 0.113
• hipred: N
• hipred_score: 0.170
• ghis: 0.438

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.564

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Matn3
• Phenotype: cellular phenotype; growth/size/body region phenotype; limbs/digits/tail phenotype; immune system phenotype; skeleton phenotype

Gene ontology

• Biological process: skeletal system development;growth plate cartilage chondrocyte morphogenesis;extracellular matrix organization;post-translational protein modification;cellular protein metabolic process
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;extracellular matrix
• Molecular function: extracellular matrix structural constituent;calcium ion binding;protein binding