GID4

Chr 17

GID complex subunit 4 homolog

Also known as: C17orf39, VID2, VID24

NCBI Gene: 79018 ENSG00000141034 UniProt: Q8IVV7 OMIM: 617699

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.

OMIM ResearchSummary from RefSeq, UniProt

The multiprotein Mediator complex is a coactivator required for activation of RNA polymerase II transcription by DNA bound transcription factors. The protein encoded by this gene is thought to be a subunit of the Mediator complex. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.38

Clinical Summary— GID4

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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.

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ClinVar Variants

28 VUS of 34 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.921

Z-score 3.02

OE 0.08 (0.03–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.10Z-score

OE missense 0.48 (0.40–0.60)

64 obs / 132.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.38)

0≤0.351.4

Missense OE?0.48 (0.40–0.60)

0≤0.61.4

Synonymous OE?0.68

0≤1.21.6

LoF obs/exp: 1 / 12.5Missense obs/exp: 64 / 132.0Syn Z: 1.87

This gene — mechanism propensity

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

34 submitted variants in ClinVar

ClinVar

Classification Summary

VUS28

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	28	0	0	28
Likely Benign	0	1	1	2
Benign	0	0	0	0
Total	28	1	1	30

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

View in ClinVar →

115 pathogenic / likely-pathogenic (of 122) ClinVar copy-number / structural variants overlap GID4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →