ZMYM5

Chr 13

zinc finger MYM-type containing 5

Also known as: HSPC050, MYM, ZNF198L1, ZNF237

The protein functions as a transcriptional regulator that binds zinc ions and negatively regulates transcription by RNA polymerase II in the nucleus. Mutations cause autosomal dominant developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and dystonia or other movement disorders. The gene shows high constraint against loss-of-function variants, suggesting intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.04
Clinical SummaryZMYM5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 76 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.46
OE 0.58 (0.341.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.06Z-score
OE missense 1.01 (0.901.14)
194 obs / 191.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.341.04)
00.351.4
Missense OE1.01 (0.901.14)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 8 / 13.9Missense obs/exp: 194 / 191.8Syn Z: -0.63
DN
0.6356th %ile
GOF
0.4480th %ile
LOF
0.3745th %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

136 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic1
VUS76
Likely Benign12
Benign5
37
Pathogenic
1
Likely Pathogenic
76
VUS
12
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
1
0
1
VUS
1
54
21
0
76
Likely Benign
0
4
8
0
12
Benign
1
0
4
0
5
Total258710131

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

View in ClinVar →

Protein Context — Lollipop Plot

ZMYM5 · 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 →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found