ZMAT3

Chr 3

zinc finger matrin-type 3

Also known as: PAG608, WIG-1, WIG1

NCBI Gene: 64393 ENSG00000172667 UniProt: Q9HA38 OMIM: 606452

This gene encodes a protein containing three zinc finger domains and a nuclear localization signal. The mRNA and the protein of this gene are upregulated by wildtype p53 and overexpression of this gene inhibits tumor cell growth, suggesting that this gene may have a role in the p53-dependent growth regulatory pathway. Alternative splicing of this gene results in two transcript variants encoding two isoforms differing in only one amino acid. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.02

Clinical Summary— ZMAT3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

28 VUS of 46 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.52

OE 0.56 (0.33–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.83 (0.72–0.96)

138 obs / 166.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.33–1.02)

0≤0.351.4

Missense OE?0.83 (0.72–0.96)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 8 / 14.2Missense obs/exp: 138 / 166.2Syn Z: 1.06

This gene — mechanism propensity

0.6357th %ile

GOF

0.5072th %ile

LOF

0.4234th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

VUS28

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	28	28
Likely Benign	3	3
Benign	0	0
Total	31	31

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap ZMAT3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →