ZMYM4

Chr 1

zinc finger MYM-type containing 4

Also known as: CDIR, MYM, ZNF198L3, ZNF262

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.17
Clinical SummaryZMYM4
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
9 unique Pathogenic / Likely Pathogenic· 129 VUS of 174 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 7.61
OE 0.10 (0.060.17)
Highly constrained

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

Missense Constraint
3.86Z-score
OE missense 0.62 (0.570.67)
499 obs / 807.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.10 (0.060.17)
00.351.4
Missense OE0.62 (0.570.67)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 8 / 82.7Missense obs/exp: 499 / 807.6Syn Z: 1.65
DN
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

174 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS129
Likely Benign1
7
Pathogenic
2
Likely Pathogenic
129
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
124
5
0
129
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total0125140139

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

View in ClinVar →

Protein Context — Lollipop Plot

ZMYM4 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC