ZNF658

Chr 9

zinc finger protein 658

NCBI Gene: 26149 ENSG00000274349 UniProt: Q5TYW1 OMIM: 616290

This gene encodes a zinc-sensitive transcriptional repressor that regulates cellular zinc homeostasis by binding to zinc transcriptional regulatory elements in gene promoters and controls ribosome biogenesis by modulating rRNA and ribosomal protein levels. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 1.9), suggesting that haploinsufficiency would be highly deleterious, but no established human disease phenotype has been reported to date. Given its critical role in zinc homeostasis and ribosome biogenesis, mutations would likely affect cellular metabolism and protein synthesis.

OMIM ResearchSummary from RefSeq, UniProt

Enables transcription cis-regulatory region binding activity. Involved in cellular response to zinc ion; negative regulation of DNA-templated transcription; and ribosome biogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.90

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.90LOEUF

pLI 0.000

Z-score -1.37

OE 1.43 (0.96–1.90)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.86Z-score

OE missense 1.42 (1.32–1.52)

529 obs / 373.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.43 (0.96–1.90)

0≤0.351.4

Missense OE?1.42 (1.32–1.52)

0≤0.61.4

Synonymous OE?1.44

0≤1.21.6

LoF obs/exp: 17 / 11.9Missense obs/exp: 529 / 373.4Syn Z: -3.94

Background carrier burden — how many people carry a rare variant somewhere in ZNF658?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 39

923 rare PASS variants

Rare truncating (LoF)

1 in 410

122 rare PASS variants

Rare synonymous (reference)

1 in 91

323 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF658. 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 40	1 in 470
South Asian	~43k	1 in 33	1 in 560
Remaining (unassigned)	~30k	1 in 39	1 in 390
European (Finnish)	~27k	1 in 200	1 in 1,600
Admixed American	~22k	1 in 55	1 in 210
African / African American	~21k	1 in 32	1 in 230
East Asian	~20k	1 in 44	1 in 230
Ashkenazi Jewish	~13k	1 in 230	1 in 860
Middle Eastern	~2,884	1 in 46	≈ 1 in 1,600

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): 2 of 4 coding exons well covered in gnomAD exomes; exons 4, 5 marginal. Genomes: 3 of 4 (exon 5 below).? see exons ↓