ZNF596

Chr 8

zinc finger protein 596

NCBI Gene: 169270 ENSG00000172748 UniProt: Q8TC21

This protein functions as a DNA-binding transcription factor that regulates RNA polymerase II transcription in the nucleus. Mutations in ZNF596 cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene shows very low constraint against loss-of-function variants (LOEUF 1.544), consistent with the recessive inheritance pattern where both copies must be affected to cause disease.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.54

LOEUF

Multiple*

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?

1.54LOEUF

pLI 0.000

Z-score -0.22

OE 1.05 (0.73–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.55Z-score

OE missense 1.44 (1.32–1.57)

381 obs / 264.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.05 (0.73–1.54)

0≤0.351.4

Missense OE?1.44 (1.32–1.57)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 19 / 18.0Missense obs/exp: 381 / 264.5Syn Z: -2.05

Background carrier burden — how many people carry a rare variant somewhere in ZNF596?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

941 rare PASS variants

Rare truncating (LoF)

1 in 540

113 rare PASS variants

Rare synonymous (reference)

1 in 170

310 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF596. 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 85	1 in 500
South Asian	~43k	1 in 41	1 in 520
Remaining (unassigned)	~30k	1 in 56	1 in 550
European (Finnish)	~27k	1 in 200	≈ 1 in 6,700
Admixed American	~22k	1 in 48	1 in 550
African / African American	~21k	1 in 53	1 in 650
East Asian	~20k	1 in 68	1 in 300
Ashkenazi Jewish	~13k	1 in 130	1 in 930
Middle Eastern	~2,884	1 in 53	1 in 360

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓