ZNF592

Chr 15

zinc finger protein 592

Also known as: CAMOS, SCAR5

NCBI Gene: 9640 ENSG00000166716 UniProt: Q92610

This gene encodes a transcription factor involved in regulating genes essential for cerebellar development. Mutations cause autosomal recessive spinocerebellar ataxia, a neurodegenerative condition primarily affecting coordination and movement due to cerebellar dysfunction. The gene is highly constrained against loss-of-function variants (pLI >0.99, LOEUF 0.133), indicating it is essential for normal cellular function.

ResearchSummary from RefSeq, UniProt

This gene is thought to play a role in a complex developmental pathway and the regulation of genes involved in cerebellar development. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia. [provided by RefSeq, Jan 2011]

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

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P/LP missense

0.13

LOEUF· LoF intol.

LOF

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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 5.37

OE 0.03 (0.01–0.13)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

0.80Z-score

OE missense 0.92 (0.86–0.98)

651 obs / 711.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.13)

0≤0.351.4

Missense OE?0.92 (0.86–0.98)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 1 / 35.6Missense obs/exp: 651 / 711.4Syn Z: -1.44

Background carrier burden — how many people carry a rare variant somewhere in ZNF592?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

1,539 rare PASS variants

Rare truncating (LoF)

1 in 7,600

40 rare PASS variants

Rare synonymous (reference)

1 in 73

679 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF592. 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 57	1 in 6,400
South Asian	~43k	1 in 34	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 39	≈ 1 in 7,500
European (Finnish)	~27k	1 in 140	1 in 3,800
Admixed American	~22k	1 in 43	none seen
African / African American	~21k	1 in 36	none seen
East Asian	~20k	1 in 50	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 150	1 in 1,400
Middle Eastern	~2,884	1 in 43	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 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓