ZNF41

Chr X

zinc finger protein 41

Also known as: MRX89

NCBI Gene: 7592ENSG00000147124UniProt: P51814OMIM: 314995

This gene encodes a transcriptional regulator containing KRAB domains and multiple zinc finger DNA-binding motifs characteristic of the Kruppel family. While an initial study suggested association with X-linked intellectual disability, subsequent research has questioned this finding. The gene shows relatively low constraint to loss-of-function variation (pLI 0.04, LOEUF 0.62), consistent with uncertain disease association.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.62
Clinical Summary— ZNF41
🧬
Gene-Disease Validity (ClinGen)
non-syndromic X-linked intellectual disability · XLDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
65 unique Pathogenic / Likely Pathogenic· 86 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.035
Z-score 2.78
OE 0.31 (0.17–0.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.30Z-score
OE missense 0.79 (0.70–0.88)
229 obs / 291.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.17–0.62)
0≤0.351.4
Missense OE0.79 (0.70–0.88)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 6 / 19.1Missense obs/exp: 229 / 291.6Syn Z: 0.38
DN
0.90top 5%
GOF
0.85top 5%
LOF
0.1993th %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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic3
VUS86
Likely Benign12
Benign7
Conflicting4
62
Pathogenic
3
Likely Pathogenic
86
VUS
12
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
3
0
3
VUS
2
73
11
0
86
Likely Benign
0
6
0
6
12
Benign
0
4
0
3
7
Conflicting
—4
Total283769174

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF41 · 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
Structural Evaluation and Conformational Dynamics of ZNF141T474I Mutation Provoking Postaxial Polydactyly Type A
Ali Y et al.·Bioengineering (Basel)
2022
Panels of mRNAs and miRNAs for decoding molecular mechanisms of Renal Cell Carcinoma (RCC) subtypes utilizing Artificial Intelligence approaches
Hosseiniyan Khatibi SM et al.·Sci Rep
2022Functional
Novel findings from family-based exome sequencing for children with biliary atresia
Tran KT et al.·Sci Rep
2021
Differential Correlation of Transcriptome Data Reveals Gene Pairs and Pathways Involved in Treatment of Citrobacter rodentium Infection with Bioactive Punicalagin
Fleming DS et al.·Molecules
2023
Screening of drug targets for tuberculosis on the basis of transcription factor regulatory network and mRNA sequencing technology
Wang S et al.·Front Mol Biosci
2024
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 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