ZNF277

Chr 7

zinc finger protein 277

Also known as: NRIF4, ZNF277P

NCBI Gene: 11179 ENSG00000198839 UniProt: Q9NRM2 OMIM: 605465

The protein is a transcription factor that represses transcription of the tumor suppressor gene INK4A/ARF and modulates cellular senescence, possibly through interaction with the Polycomb group complex PRC1. Based on the extremely low pLI score and high LOEUF value, this gene appears highly tolerant to loss-of-function mutations, suggesting pathogenic variants are unlikely to cause disease through haploinsufficiency. No established neurogenetic disorders have been associated with ZNF277 mutations.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to be involved in DNA-templated transcription. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.56

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.56LOEUF

pLI 0.000

Z-score -0.70

OE 1.15 (0.86–1.56)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.94 (0.84–1.05)

213 obs / 227.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.15 (0.86–1.56)

0≤0.351.4

Missense OE?0.94 (0.84–1.05)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 30 / 26.1Missense obs/exp: 213 / 227.8Syn Z: 0.10

Background carrier burden — how many people carry a rare variant somewhere in ZNF277?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

586 rare PASS variants

Rare truncating (LoF)

1 in 350

116 rare PASS variants

Rare synonymous (reference)

1 in 220

200 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ZNF277; this gene does not show strong loss-of-function constraint by this measure. 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 190	1 in 1,300
South Asian	~43k	1 in 140	1 in 710
Remaining (unassigned)	~30k	1 in 120	1 in 300
European (Finnish)	~27k	1 in 580	1 in 700
Admixed American	~22k	1 in 120	1 in 530
African / African American	~21k	1 in 150	1 in 650
East Asian	~20k	1 in 86	1 in 380
Ashkenazi Jewish	~13k	1 in 810	1 in 730
Middle Eastern	~2,884	1 in 170	≈ 1 in 950

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): 11 of 12 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: 11 of 12 (exon 2 below).? see exons ↓