ARHGDIA

Chr 17AR

Rho GDP dissociation inhibitor alpha

Also known as: GDIA1, HEL-S-47e, NPHS8, RHOGDI, RHOGDI-1

The protein encoded by this gene controls Rho GTPase homeostasis by inhibiting GDP dissociation and maintaining these signaling molecules in an inactive cytosolic pool. Mutations cause autosomal recessive nephrotic syndrome type 8, affecting kidney function. The gene shows relatively low constraint to loss-of-function mutations (pLI 0.036, LOEUF 0.87).

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.871 OMIM phenotype
Clinical SummaryARHGDIA
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Gene-Disease Validity (ClinGen)
nephrotic syndrome, type 8 · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.036
Z-score 1.86
OE 0.38 (0.190.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.20Z-score
OE missense 0.70 (0.580.83)
87 obs / 124.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.190.87)
00.351.4
Missense OE0.70 (0.580.83)
00.61.4
Synonymous OE1.57
01.21.6
LoF obs/exp: 4 / 10.5Missense obs/exp: 87 / 124.9Syn Z: -3.35
DN
0.6162th %ile
GOF
0.5170th %ile
LOF
0.2680th %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

ARHGDIA · 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.

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Clinical Literature
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