ZNF785

Chr 16

zinc finger protein 785

NCBI Gene: 146540 ENSG00000197162 UniProt: A8K8V0

The protein is predicted to function as a DNA-binding transcription factor that regulates RNA polymerase II-mediated transcription in the nucleus. Based on the gene's extremely low constraint against loss-of-function variants (pLI near 0, LOEUF 1.94), pathogenic variants in ZNF785 are not currently established as a cause of human disease. No specific disease associations or inheritance patterns have been documented for this gene.

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…

MultiplemechanismLOEUF 1.94

Clinical Summary— ZNF785

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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

56 VUS of 64 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.94LOEUF

pLI 0.000

Z-score -1.16

OE 1.60 (0.83–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.53Z-score

OE missense 0.91 (0.82–1.01)

250 obs / 274.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.60 (0.83–1.94)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 7 / 4.4Missense obs/exp: 250 / 274.6Syn Z: 1.22

This gene — mechanism propensity

0.6454th %ile

GOF

0.7127th %ile

LOF

0.3842th %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

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS56

Likely Benign2

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	56	0	56
Likely Benign	1	1	2
Benign	0	0	0
Total	57	1	58

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ZNF785 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →