ZNF292

Chr 6AD

zinc finger protein 292

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

NCBI Gene: 23036ENSG00000188994UniProt: O60281

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]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 64MIM #619188
AD
877
ClinVar variants
30
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— ZNF292
⚡
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.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 365 VUS of 877 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.41Z-score
OE missense 0.89 (0.85–0.94)
1203 obs / 1348.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.04–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.85–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 7 / 93.8Missense obs/exp: 1203 / 1348.5Syn Z: -2.14

ClinVar Variant Classifications

877 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic14
VUS365
Likely Benign173
Benign8
Conflicting6
16
Pathogenic
14
Likely Pathogenic
365
VUS
173
Likely Benign
8
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
7
0
16
Likely Pathogenic
6
0
8
0
14
VUS
3
340
19
3
365
Likely Benign
0
118
4
51
173
Benign
0
3
0
5
8
Conflicting
—6
Total184613859582

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF292 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ZNF292-related developmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 64

MIM #619188

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo genic mutations among a Chinese autism spectrum disorder cohort.
Wang T et al.·Nat Commun
2016Cohort
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo H et al.·Mol Autism
2018Functional
Non-coding recurrent mutations in chronic lymphocytic leukaemia.
Puente XS et al.·Nature
2015
A genomic and epigenomic atlas of prostate cancer in Asian populations.
Li J et al.·Nature
2020
De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder.
Mirzaa GM et al.·Genet Med
2020
Requirements for the neurodevelopmental disorder-associated gene ZNF292 in human cortical interneuron development and function.
Kaushik K et al.·Cell Rep
2025
Rare Causes and Differential Diagnosis in Patients With Silver-Russell Syndrome.
Braga BL et al.·Clin Genet
2025Cohort
Porphyromonas gingivalis outer membrane vesicles augments proliferation and metastasis of oral squamous cell carcinoma cells.
Zeng Y et al.·BMC Oral Health
2025
Patterns of Gene Expression, Splicing, and Allele-Specific Expression Vary among Macular Tissues and Clinical Stages of Age-Related Macular Degeneration.
Shwani T et al.·Cells
2023
Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech.
Ormieres C et al.·Mol Autism
2025Clinical trial
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools