GLI4

Chr 8

GLI family zinc finger 4

Also known as: HKR4, ZNF928

NCBI Gene: 2738ENSG00000250571UniProt: P10075

The protein is predicted to function as a DNA-binding transcription factor that regulates gene transcription by binding to specific DNA sequences and interacting with RNA polymerase II. This gene is not well-constrained against loss-of-function variants (pLI = 0.002, LOEUF = 0.98), suggesting it may tolerate such variants in the general population. Currently, no established human diseases or clear inheritance patterns have been definitively associated with GLI4 mutations in the literature.

Summary from RefSeq
Research Assistant →
0
Active trials
1
Pubs (1 yr)
61
P/LP submissions
0%
P/LP missense
0.98
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— GLI4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 106 VUS of 176 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.002
Z-score 1.61
OE 0.50 (0.27–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.68Z-score
OE missense 1.13 (1.02–1.26)
238 obs / 210.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.50 (0.27–0.98)
0≤0.351.4
Missense OE1.13 (1.02–1.26)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 6 / 12.0Missense obs/exp: 238 / 210.3Syn Z: -1.02
DN
0.91top 5%
GOF
0.84top 5%
LOF
0.2483th %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

176 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic5
VUS106
Likely Benign2
55
Pathogenic
5
Likely Pathogenic
106
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
55
0
55
Likely Pathogenic
0
0
5
0
5
VUS
0
96
10
0
106
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total098700168

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

View in ClinVar →

Protein Context — Lollipop Plot

GLI4 · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 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