ZNF680

Chr 7

zinc finger protein 680

NCBI Gene: 340252 ENSG00000173041 UniProt: Q8NEM1

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 DNA-templated transcription. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.420

Z-score 1.72

OE 0.19 (0.07–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.12Z-score

OE missense 0.98 (0.88–1.09)

258 obs / 263.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.07–0.90)

0≤0.351.4

Missense OE?0.98 (0.88–1.09)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 1 / 5.2Missense obs/exp: 258 / 263.3Syn Z: 1.47

Background carrier burden — how many people carry a rare variant somewhere in ZNF680?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

665 rare PASS variants

Rare truncating (LoF)

1 in 1,300

95 rare PASS variants

Rare synonymous (reference)

1 in 360

211 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF680. 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 150	1 in 1,300
South Asian	~43k	1 in 62	1 in 920
Remaining (unassigned)	~30k	1 in 73	1 in 750
European (Finnish)	~27k	1 in 690	≈ 1 in 13,000
Admixed American	~22k	1 in 72	1 in 1,600
African / African American	~21k	1 in 120	1 in 870
East Asian	~20k	1 in 200	1 in 900
Ashkenazi Jewish	~13k	1 in 320	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 140	none seen

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