ZNF81

Chr X

zinc finger protein 81

Also known as: HFZ20, MRX45, dJ54B20.6

NCBI Gene: 347344ENSG00000197779UniProt: P51508OMIM: 314998

This gene encodes a transcription factor containing a KRAB domain and multiple C2H2-type zinc finger motifs. Mutations cause X-linked intellectual disability (MRX45), and microduplications involving this gene are also associated with intellectual disability. The gene shows X-linked inheritance and is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.51
Clinical Summary— ZNF81
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Gene-Disease Validity (ClinGen)
X-linked intellectual disability · XLDisputed

Disputed — evidence questions this relationship

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.
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ClinVar Variants
62 unique Pathogenic / Likely Pathogenic· 56 VUS of 144 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.554
Z-score 2.92
OE 0.20 (0.09–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.42Z-score
OE missense 0.74 (0.65–0.84)
168 obs / 228.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.09–0.51)
0≤0.351.4
Missense OE0.74 (0.65–0.84)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 3 / 15.4Missense obs/exp: 168 / 228.5Syn Z: 0.67
DN
0.82top 10%
GOF
0.81top 10%
LOF
0.3355th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

144 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic2
VUS56
Likely Benign6
Benign9
Conflicting2
60
Pathogenic
2
Likely Pathogenic
56
VUS
6
Likely Benign
9
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
2
0
2
VUS
0
46
10
0
56
Likely Benign
0
3
0
3
6
Benign
0
4
1
4
9
Conflicting
—2
Total053737135

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF81 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Do extracellular vesicles have specific target cells?; Extracellular vesicle mediated embryo maternal communication
Dissanayake K et al.·Front Mol Biosci
2024
Comprehensive analysis of ceRNA networks in HPV16- and HPV18-mediated cervical cancers reveals XIST as a pivotal competing endogenous RNA.
Berti FCB et al.·Biochim Biophys Acta Mol Basis Dis
2021
Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis
Membrive Jiménez C et al.·J Pers Med
2021
Late relapse of chronic myeloid leukemia after allogeneic bone marrow transplantation points to KANSARL (KANSL1::ARL17A) alteration: a case report with insights on the molecular landscape
Fontana D et al.·Ann Hematol
2024Case report
Autism Spectrum Disorder in Pediatric Idiopathic Intracranial Hypertension
Jensen AK et al.·Life (Basel)
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients