ZMYM2

Chr 13AD

zinc finger MYM-type containing 2

Also known as: FIM, MYM, NECRC, RAMP, SCLL, ZNF198

NCBI Gene: 7750ENSG00000121741UniProt: Q9UBW7OMIM: 602221

The encoded zinc finger protein functions as a transcriptional repressor and is part of a histone deacetylase complex involved in chromatin regulation. Mutations cause neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.332), reflecting its critical role in normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.331 OMIM phenotype
Clinical Summary— ZMYM2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
89 unique Pathogenic / Likely Pathogenic· 167 VUS of 295 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.666
Z-score 6.06
OE 0.22 (0.14–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.01Z-score
OE missense 0.67 (0.62–0.73)
451 obs / 670.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.22 (0.14–0.33)
0≤0.351.4
Missense OE0.67 (0.62–0.73)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 15 / 69.5Missense obs/exp: 451 / 670.7Syn Z: 1.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongZMYM2-related developmental disorderLOFAD
DN
0.3296th %ile
GOF
0.3094th %ile
LOF
0.67top 25%

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

LOFprediction above median · 1 literature citation · 55% of P/LP variants are LoF · LOEUF 0.33

Literature Evidence

LOFThrough collaboration, we identified in total 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families.PMID:32891193

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

295 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic31
VUS167
Likely Benign24
Benign11
Conflicting2
58
Pathogenic
31
Likely Pathogenic
167
VUS
24
Likely Benign
11
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
0
36
0
58
Likely Pathogenic
27
0
4
0
31
VUS
12
132
23
0
167
Likely Benign
0
6
7
11
24
Benign
0
1
5
5
11
Conflicting
—2
Total611397516293

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

View in ClinVar →

Protein Context — Lollipop Plot

ZMYM2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
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