ZNF141

Chr 4AR

zinc finger protein 141

Also known as: D4S90, pHZ-44

NCBI Gene: 7700ENSG00000131127UniProt: Q15928

The protein is a zinc finger transcriptional repressor involved in limb development. Mutations cause autosomal recessive postaxial polydactyly type A6, characterized by extra digits on the pinky side of hands or feet. The gene shows autosomal recessive inheritance with relatively low constraint to loss-of-function variants.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Polydactyly, postaxial, type A6MIM #615226
AR
0
Active trials
0
Pubs (1 yr)
140
P/LP submissions
1%
P/LP missense
1.25
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ZNF141
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
139 unique Pathogenic / Likely Pathogenic· 82 VUS of 267 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
1.25LOEUF
pLI 0.104
Z-score 1.23
OE 0.40 (0.16–1.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.22Z-score
OE missense 0.96 (0.86–1.07)
232 obs / 241.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.16–1.25)
0≤0.351.4
Missense OE0.96 (0.86–1.07)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 2 / 5.0Missense obs/exp: 232 / 241.8Syn Z: 0.05
DN
0.93top 5%
GOF
0.91top 5%
LOF
0.1796th %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

267 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic134
Likely Pathogenic5
VUS82
Likely Benign19
Benign15
Conflicting2
134
Pathogenic
5
Likely Pathogenic
82
VUS
19
Likely Benign
15
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
134
0
134
Likely Pathogenic
0
1
4
0
5
VUS
0
55
27
0
82
Likely Benign
0
6
8
5
19
Benign
2
10
1
2
15
Conflicting
—2
Total2721747257

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF141 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Development and validation of novel prognostic models for zinc finger proteins-related genes in soft tissue sarcoma
Li J et al.·Aging (Albany NY)
2023Functional
A novel homozygous FAM92A gene (CIBAR1) variant further confirms its association with non-syndromic postaxial polydactyly type A9 (PAPA9).
Umair M et al.·Clin Genet
2024
A Novel Homozygous Missense Mutation in the Zinc Finger DNA Binding Domain of GLI1 Causes Recessive Post-Axial Polydactyly
Umair M et al.·Front Genet
2021
A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes.
Bakar A et al.·Eur J Med Genet
2022
Identification of the susceptible genes and mechanism underlying the comorbid presence of coronary artery disease and rheumatoid arthritis: a network modularization analysis
Zhang S et al.·BMC Genomics
2023Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 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