ZNF774

Chr 15

zinc finger protein 774

NCBI Gene: 342132 ENSG00000196391 UniProt: Q6NX45

The protein is predicted to function as a DNA-binding transcription factor that regulates RNA polymerase II-mediated transcription in the nucleus. Currently, no specific genetic diseases have been definitively associated with ZNF774 mutations in clinical practice. The gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting it may tolerate such changes without causing severe disease.

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 transcription by RNA polymerase II. Located in intermediate filament cytoskeleton. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.48

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?

1.48LOEUF

pLI 0.000

Z-score -0.17

OE 1.04 (0.74–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.17Z-score

OE missense 0.97 (0.88–1.08)

261 obs / 268.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.04 (0.74–1.48)

0≤0.351.4

Missense OE?0.97 (0.88–1.08)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 22 / 21.2Missense obs/exp: 261 / 268.8Syn Z: 1.61

Background carrier burden — how many people carry a rare variant somewhere in ZNF774?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

663 rare PASS variants

Rare truncating (LoF)

1 in 1,200

119 rare PASS variants

Rare synonymous (reference)

1 in 430

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF774. 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 88	1 in 1,600
South Asian	~43k	1 in 96	1 in 410
Remaining (unassigned)	~30k	1 in 87	1 in 540
European (Finnish)	~27k	1 in 350	1 in 460
Admixed American	~22k	1 in 92	1 in 960
African / African American	~21k	1 in 60	1 in 570
East Asian	~20k	1 in 71	1 in 730
Ashkenazi Jewish	~13k	1 in 490	1 in 1,600
Middle Eastern	~2,884	1 in 71	≈ 1 in 710

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓