ZMYM3

Chr XXLR

zinc finger MYM-type containing 3

Also known as: DXS6673E, MYM, XFIM, XLID112, ZNF198L2, ZNF261

NCBI Gene: 9203ENSG00000147130UniProt: Q14202

This gene is located on the X chromosome and is subject to X inactivation. It is highly conserved in vertebrates and most abundantly expressed in the brain. The encoded protein is a component of histone deacetylase-containing multiprotein complexes that function through modifying chromatin structure to keep genes silent. A chromosomal translocation (X;13) involving this gene is associated with X-linked cognitive disability. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2010]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 112MIM #301111
XLR
0
Active trials
20
Pathogenic / LP
199
ClinVar variants
6
Pubs (1 yr)
4.3
Missense Z· constrained
0.11
LOEUF· LoF intolerant
Clinical Summary— ZMYM3
⚡
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
20 Pathogenic / Likely Pathogenic· 156 VUS of 199 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 6.05
OE 0.02 (0.01–0.11)
Highly constrained

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

Missense Constraint
4.31Z-score
OE missense 0.48 (0.43–0.53)
261 obs / 543.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.01–0.11)
0≤0.351.4
Missense OE0.48 (0.43–0.53)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 1 / 44.6Missense obs/exp: 261 / 543.5Syn Z: -0.30
LOF
DN
0.17100th %ile
GOF
0.2995th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.11

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic8
VUS156
Likely Benign21
Conflicting2
12
Pathogenic
8
Likely Pathogenic
156
VUS
21
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
9
1
12
Likely Pathogenic
0
8
0
0
8
VUS
5
142
7
2
156
Likely Benign
0
3
3
15
21
Benign
0
0
0
0
0
Conflicting
—2
Total71531918199

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

View in ClinVar →

ZMYM3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ZMYM3-related neurodevelopmental disorder

moderate
Monoallelic X HeterozygousUndeterminedAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
missense variantframeshift variant NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients