ZNF764

Chr 16

zinc finger protein 764

NCBI Gene: 92595 ENSG00000169951 UniProt: Q96H86

ZNF764 encodes a zinc finger protein that functions as a cofactor for steroid hormone receptors, particularly the glucocorticoid receptor, directing its transcriptional activity toward specific biological pathways. Mutations cause autosomal recessive developmental delay with seizures and corpus callosum abnormalities. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

ResearchSummary from RefSeq, UniProt

Enables transcription coregulator activity. Involved in cellular response to glucocorticoid stimulus. Is active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.17

Clinical Summary— ZNF764

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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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ClinVar Variants

78 VUS of 87 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.17LOEUF

pLI 0.000

Z-score 1.14

OE 0.65 (0.38–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.45Z-score

OE missense 1.08 (0.98–1.19)

288 obs / 267.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.38–1.17)

0≤0.351.4

Missense OE?1.08 (0.98–1.19)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 8 / 12.3Missense obs/exp: 288 / 267.4Syn Z: -0.51

This gene — mechanism propensity

0.7326th %ile

GOF

0.80top 10%

LOF

0.3065th %ile

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

GOFprediction above median

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

87 submitted variants in ClinVar

ClinVar

Classification Summary

VUS78

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	78	78
Likely Benign	6	6
Benign	0	0
Total	84	84

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap ZNF764 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →