GID4

Chr 17

GID complex subunit 4 homolog

Also known as: C17orf39, VID2, VID24

The protein functions as a substrate-recognition subunit of the CTLH E3 ubiquitin-protein ligase complex, mediating ubiquitination and proteasomal degradation of specific proteins including the transcription factor HBP1. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.38
Clinical SummaryGID4
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
115 unique Pathogenic / Likely Pathogenic· 33 VUS of 156 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.921
Z-score 3.02
OE 0.08 (0.030.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.10Z-score
OE missense 0.48 (0.400.60)
64 obs / 132.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.030.38)
00.351.4
Missense OE0.48 (0.400.60)
00.61.4
Synonymous OE0.68
01.21.6
LoF obs/exp: 1 / 12.5Missense obs/exp: 64 / 132.0Syn Z: 1.87
DN
0.3494th %ile
GOF
0.3986th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.38

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

156 submitted variants in ClinVar

Classification Summary

Pathogenic115
VUS33
Likely Benign3
115
Pathogenic
33
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
115
0
115
Likely Pathogenic
0
0
0
0
0
VUS
0
28
5
0
33
Likely Benign
0
0
2
1
3
Benign
0
0
0
0
0
Total0281221151

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

View in ClinVar →

Protein Context — Lollipop Plot

GID4 · 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

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
Top 5 full-text resultsSearch PubTator3 ↗