ZNF292

Chr 6

zinc finger protein 292

Also known as: MRD63, MRD64, Nbla00365, ZFP292, ZN-16, Zn-15, bA393I2.3

NCBI Gene: 23036 ENSG00000188994 UniProt: O60281

This gene encodes a zinc finger transcription factor involved in transcriptional regulation. Mutations cause autosomal dominant intellectual developmental disorder, with the gene being highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.14). The inheritance pattern is autosomal dominant.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a growth hormone-dependent, zinc finger transcription factor that functions as a tumor suppressor. Naturally occurring mutations in this gene are associated with gastric cancer, colorectal cancer, and chronic lymphocytic leukemia. [provided by RefSeq, May 2017]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— ZNF292

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

105 unique Pathogenic / Likely Pathogenic· 492 VUS of 874 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.14LOEUF

pLI 1.000

Z-score 8.30

OE 0.07 (0.04–0.14)

Highly constrained

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

Missense Constraint?

1.41Z-score

OE missense 0.89 (0.85–0.94)

1203 obs / 1348.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.07 (0.04–0.14)

0≤0.351.4

Missense OE?0.89 (0.85–0.94)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 7 / 93.8Missense obs/exp: 1203 / 1348.5Syn Z: -2.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongZNF292-related developmental disorderLOFAD

This gene — mechanism propensity

0.2499th %ile

GOF

0.16100th %ile

LOF

0.82top 5%

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

LOFprediction above median · 95% of P/LP variants are LoF · LOEUF 0.14

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

874 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36

Likely Pathogenic69

VUS492

Likely Benign217

Benign24

Conflicting18

Pathogenic

Likely Pathogenic

492

VUS

217

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	36	0	0	0	36
Likely Pathogenic	64	4	1	0	69
VUS	18	465	6	3	492
Likely Benign	1	149	2	65	217
Benign	0	12	1	11	24
Conflicting	—				18
Total	119	630	10	79	856

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap ZNF292 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →