GID8

Chr 20

GID complex subunit 8 homolog

Also known as: C20orf11, TWA1

NCBI Gene: 54994ENSG00000101193UniProt: Q9NWU2

The GID8 protein is a core component of the CTLH E3 ubiquitin ligase complex that regulates protein degradation and acts as a positive regulator of Wnt signaling by promoting beta-catenin nuclear accumulation. This gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.36), but no specific Mendelian diseases have been definitively associated with GID8 mutations to date. Additional clinical and genetic evidence is needed to establish clear genotype-phenotype correlations for this gene.

Summary from RefSeq, UniProt
Research Assistant →
LOEUF 0.36
Clinical Summary— GID8
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 36 VUS of 77 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.36LOEUF
pLI 0.940
Z-score 3.13
OE 0.08 (0.03–0.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.47Z-score
OE missense 0.41 (0.33–0.51)
57 obs / 139.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.03–0.36)
0≤0.351.4
Missense OE0.41 (0.33–0.51)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 1 / 13.3Missense obs/exp: 57 / 139.0Syn Z: -0.27

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic6
VUS36
Likely Benign2
26
Pathogenic
6
Likely Pathogenic
36
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
6
0
6
VUS
0
20
16
0
36
Likely Benign
0
0
2
0
2
Benign
0
0
0
0
0
Total02050070

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

View in ClinVar →

Protein Context — Lollipop Plot

GID8 · 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.

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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 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