MATN4

protein-coding

matrilin 4, the group of Matrilins

Gene summary

This gene encodes a member of von Willebrand factor A domain-containing protein family. The proteins of this family are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This family member is thought to be play a role in reorganizing and regenerating the corneal matrix in granular and lattice type I dystrophies. It may also be involved in wound healing in the dentin-pulp complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

MANE transcript

NM_001393530.1

Inheritance

—

ClinVar variants

P:1U:90B:10

Top phenotype

MATN4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr20:45,293,445-45,308,529

External References & Databases

Ensembl (ENSG00000124159)

Transcript & Mutation Effects

hg38 • Region Span ~15.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MATN4 variants in ClinVar

11 Conditions Cataloged

not specifiedTotal: 90

MATN4-related disorderTotal: 10

not providedTotal: 5

Type 2 diabetes mellitusTotal: 2

Holoprosencephaly sequenceTotal: 2

Diabetes insipidusTotal: 1

SeizureTotal: 1

Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001393530.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	2 clinvar	3
missense		1 clinvar	89 clinvar	2 clinvar	4 clinvar	96
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	90	4	6	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001393530.1	RefSeq	NP_001380459.1	9	MANE Select
ENST00000372756.6	Ensembl	ENSP00000361842.1	9	MANE Select
NM_001393531.1	RefSeq	NP_001380460.1	8	Standard
NM_003833.5	RefSeq	NP_003824.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Extracellular matrix organization
ECM proteoglycans

Biological Process

growth plate cartilage chondrocyte morphogenesis
extracellular matrix organization

Molecular Function

calcium ion binding
protein binding

Cellular Component

extracellular region
extracellular space
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000537548
Coding exons: 9
Length: 15085
Individuals with no LoFs: 125404
Homozygous LoFs: 2
Heterozygous LoFs: 342
Defined: 125748
p: 0.00137

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.12	340	404	0.843	0.0000289	3709
Missense (PolyPhen)		136	171.31	0.79387		1553
Synonymous	2.05	148	183	0.807	0.0000145	1203
Loss of Function	1.49	16	23.8	0.672	0.00000127	237

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.0016	0.0016	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00023	0.00022	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0021	0.0021	notable
South Asian	0.00073	0.00072	rare
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major component of the extracellular matrix of cartilage.;

Intolerance Scores

LoFtool: 0.122
RVIS EVS: 1.29
RVIS percentile EVS: 93.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.783

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High