ZNF771

Chr 16

zinc finger protein 771

Also known as: DSC43

NCBI Gene: 51333 ENSG00000179965 UniProt: Q7L3S4

The ZNF771 protein enables sequence-specific double-stranded DNA binding and is involved in transcriptional regulation by RNA polymerase II. Mutations cause autosomal recessive intellectual disability with seizures and brain malformations, typically presenting in infancy or early childhood. The gene shows low constraint to loss-of-function variants, which is consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.02

Clinical Summary— ZNF771

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Population Constraint (gnomAD)

Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 VUS of 37 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?

1.02LOEUF

pLI 0.060

Z-score 1.55

OE 0.39 (0.18–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

2.06Z-score

OE missense 0.45 (0.36–0.57)

50 obs / 111.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.39 (0.18–1.02)

0≤0.351.4

Missense OE?0.45 (0.36–0.57)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 3 / 7.6Missense obs/exp: 50 / 111.0Syn Z: -1.40

This gene — mechanism propensity

0.6936th %ile

GOF

0.74top 25%

LOF

0.3258th %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

37 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	34	0	34
Likely Benign	0	1	1
Benign	0	0	0
Total	34	1	35

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ZNF771 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →