IDH3G

Chr XXLR

isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit gamma

Also known as: H-IDHG, RP99

The protein is the gamma subunit of NAD(+)-dependent isocitrate dehydrogenase, which catalyzes the rate-limiting step of the tricarboxylic acid cycle by decarboxylating isocitrate to alpha-ketoglutarate in the mitochondrial matrix. Mutations cause retinitis pigmentosa 99, inherited in an X-linked recessive pattern. The pathogenic mechanism appears to be dominant-negative, where mutant protein disrupts the normal function of the heterotetrameric enzyme complex.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Retinitis pigmentosa 99MIM #301148
XLR
0
Active trials
8
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.71
LOEUF
DN
Mechanism· predicted
Clinical SummaryIDH3G
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.085
Z-score 2.29
OE 0.31 (0.150.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.19Z-score
OE missense 0.56 (0.470.65)
107 obs / 192.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.31 (0.150.71)
00.351.4
Missense OE0.56 (0.470.65)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 4 / 12.9Missense obs/exp: 107 / 192.7Syn Z: -0.20
DN
0.76top 25%
GOF
0.5856th %ile
LOF
0.3843th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IDH3G · 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC