ZNF592

Chr 15

zinc finger protein 592

Also known as: CAMOS, SCAR5

NCBI Gene: 9640 ENSG00000166716 UniProt: Q92610 OMIM: 613624

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.13

Clinical Summary— ZNF592

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

185 VUS of 225 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.2898th %ile

GOF

0.2796th %ile

LOF

0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.13

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

225 submitted variants in ClinVar

ClinVar

Classification Summary

VUS185

Likely Benign19

Benign9

Conflicting1

185

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	183	0	1	185
Likely Benign	0	12	0	7	19
Benign	0	5	2	2	9
Conflicting	—				1
Total	1	200	2	10	214

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

32 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap ZNF592 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →