MATR3

Chr 5AD

matrin 3

Also known as: ALS21, MPD2, VCPDM

NCBI Gene: 9782ENSG00000015479UniProt: P43243

This gene encodes a nuclear matrix protein, which is proposed to stabilize certain messenger RNA species. Mutations of this gene are associated with distal myopathy 2, which often includes vocal cord and pharyngeal weakness. Alternatively spliced transcript variants, including read-through transcripts composed of the upstream small nucleolar RNA host gene 4 (non-protein coding) and matrin 3 gene sequence, have been identified. Pseudogenes of this gene are located on chromosomes 1 and X. [provided by RefSeq, Aug 2013]

Primary Disease Associations & Inheritance

Amyotrophic lateral sclerosis 21MIM #606070
AD
666
ClinVar variants
8
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MATR3
🧬
Gene-Disease Validity (ClinGen)
distal myopathy with vocal cord weakness · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 356 VUS of 666 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.08LOEUF
pLI 1.000
Z-score 5.68
OE 0.00 (0.00–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.73Z-score
OE missense 0.64 (0.58–0.70)
289 obs / 452.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.58–0.70)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 0 / 37.5Missense obs/exp: 289 / 452.4Syn Z: 0.01

ClinVar Variant Classifications

666 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS356
Likely Benign244
Benign48
Conflicting10
7
Pathogenic
1
Likely Pathogenic
356
VUS
244
Likely Benign
48
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
6
276
70
4
356
Likely Benign
0
6
108
130
244
Benign
0
1
45
2
48
Conflicting
—10
Total6283231136666

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MATR3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
MATRIN 3; MATR3
MIM #164015 · *

Amyotrophic lateral sclerosis 21

MIM #606070

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — MATR3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Panorama of the distal myopathies.
Savarese M et al.·Acta Myol
2020Review
Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications.
Chia R et al.·Lancet Neurol
2018Review
Matrin 3 in neuromuscular disease: physiology and pathophysiology.
Malik AM et al.·JCI Insight
2021Review
MATR3 pathogenic variants differentially impair its cryptic splicing repression function.
Khan M et al.·FEBS Lett
2024
Autosomal dominant distal myopathy due to p.Ser85Cys mutation in the MATR3 gene: Novel case series and literature review.
Chitimus DM et al.·Rev Neurol (Paris)
2025Review
RNA-recognition motif in Matrin-3 mediates neurodegeneration through interaction with hnRNPM.
Ramesh N et al.·Acta Neuropathol Commun
2020
Analysis of spinal and muscle pathology in transgenic mice overexpressing wild-type and ALS-linked mutant MATR3.
Moloney C et al.·Acta Neuropathol Commun
2018
Multisystem proteinopathies (MSPs) and MSP-like disorders: Clinical-pathological-molecular spectrum.
Chompoopong P et al.·Ann Clin Transl Neurol
2023
Multisystem proteinopathy: Where myopathy and motor neuron disease converge.
Korb MK et al.·Muscle Nerve
2021Review
Knockdown of genes involved in axonal transport enhances the toxicity of human neuromuscular disease-linked MATR3 mutations in Drosophila.
Zhao M et al.·FEBS Lett
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools