ZMYM4

Chr 1

zinc finger MYM-type containing 4

Also known as: CDIR, MYM, ZNF198L3, ZNF262

NCBI Gene: 9202 ENSG00000146463 UniProt: Q5VZL5 OMIM: 613568

ZMYM4 encodes a DNA-binding protein that regulates cell morphology and cytoskeletal organization. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and distinctive facial features. This gene is highly constrained against loss-of-function mutations (pLI = 1.0, LOEUF = 0.175), indicating critical developmental importance.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.17

Clinical Summary— ZMYM4

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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.

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ClinVar Variants

124 VUS of 160 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 7.61

OE 0.10 (0.06–0.17)

Highly constrained

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

Missense Constraint?

3.86Z-score

OE missense 0.62 (0.57–0.67)

499 obs / 807.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.06–0.17)

0≤0.351.4

Missense OE?0.62 (0.57–0.67)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 8 / 82.7Missense obs/exp: 499 / 807.6Syn Z: 1.65

This gene — mechanism propensity

0.2099th %ile

GOF

0.2397th %ile

LOF

0.80top 5%

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

LOFprediction above median · LOEUF 0.17

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

160 submitted variants in ClinVar

ClinVar

Classification Summary

VUS124

Likely Benign1

124

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	124	124
Likely Benign	1	1
Benign	0	0
Total	125	125

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap ZMYM4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →