ZNF695

Chr 1

zinc finger protein 695

Also known as: SBZF3

NCBI Gene: 57116 ENSG00000197472 UniProt: Q8IW36 OMIM: 616348

The protein is predicted to function as a DNA-binding transcription factor that regulates gene expression by binding to specific DNA sequences and controlling RNA polymerase II-mediated transcription in the nucleus. Currently, no established human diseases have been definitively linked to mutations in this gene. The gene appears to be tolerant to loss-of-function variants based on constraint metrics, suggesting that complete loss of function may not cause severe developmental phenotypes.

OMIM ResearchSummary from RefSeq, UniProt

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

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.85

Clinical Summary— ZNF695

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.000

Z-score -0.16

OE 1.08 (0.55–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.17Z-score

OE missense 0.97 (0.87–1.08)

240 obs / 247.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.08 (0.55–1.85)

0≤0.351.4

Missense OE?0.97 (0.87–1.08)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 5 / 4.6Missense obs/exp: 240 / 247.6Syn Z: 0.77

This gene — mechanism propensity

0.92top 5%

GOF

0.84top 5%

LOF

0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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.