ZMYM5

Chr 13

zinc finger MYM-type containing 5

Also known as: HSPC050, MYM, ZNF198L1, ZNF237

NCBI Gene: 9205 ENSG00000132950 UniProt: Q9UJ78

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.

ResearchSummary from RefSeq, UniProt

Predicted to enable zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.46

OE 0.58 (0.34–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.01 (0.90–1.14)

194 obs / 191.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.58 (0.34–1.04)

0≤0.351.4

Missense OE?1.01 (0.90–1.14)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 8 / 13.9Missense obs/exp: 194 / 191.8Syn Z: -0.63

Background carrier burden — how many people carry a rare variant somewhere in ZMYM5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

833 rare PASS variants

Rare truncating (LoF)

1 in 500

134 rare PASS variants

Rare synonymous (reference)

1 in 180

286 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZMYM5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 77	1 in 520
South Asian	~43k	1 in 94	1 in 270
Remaining (unassigned)	~30k	1 in 57	1 in 400
European (Finnish)	~27k	1 in 230	1 in 2,900
Admixed American	~22k	1 in 71	1 in 820
African / African American	~21k	1 in 65	1 in 350
East Asian	~20k	1 in 69	1 in 520
Ashkenazi Jewish	~13k	1 in 270	1 in 370
Middle Eastern	~2,884	1 in 78	1 in 580

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 6 coding exons well covered in gnomAD exomes; exons 7, 8 marginal. Genomes: all 6.? see exons ↓