ZNF692

Chr 1

zinc finger protein 692

Also known as: AREBP, Zfp692

NCBI Gene: 55657 ENSG00000171163 UniProt: Q9BU19

ZNF692 encodes a transcriptional repressor that regulates gluconeogenesis by suppressing PCK1 gene expression through AMPK signaling pathways. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia, seizures, and abnormal glucose metabolism, typically manifesting in infancy or early childhood. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II and regulation of gluconeogenesis. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.22

Clinical Summary— ZNF692

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

86 VUS of 109 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 0.75

OE 0.83 (0.58–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.85Z-score

OE missense 0.86 (0.78–0.96)

257 obs / 298.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.58–1.22)

0≤0.351.4

Missense OE?0.86 (0.78–0.96)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 19 / 22.8Missense obs/exp: 257 / 298.1Syn Z: -0.41

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

VUS86

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	86	0	86
Likely Benign	3	0	3
Benign	0	1	1
Total	89	1	90

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

View in ClinVar →

66 pathogenic / likely-pathogenic (of 77) ClinVar copy-number / structural variants overlap ZNF692 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →