ARHGDIA

Chr 17AR

Rho GDP dissociation inhibitor alpha

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

NCBI Gene: 396ENSG00000141522UniProt: P52565

This gene encodes a protein that plays a key role in the regulation of signaling through Rho GTPases. The encoded protein inhibits the disassociation of Rho family members from GDP (guanine diphosphate), thereby maintaining these factors in an inactive state. Activity of this protein is important in a variety of cellular processes, and expression of this gene may be altered in tumors. Mutations in this gene have been found in individuals with nephrotic syndrome, type 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Nephrotic syndrome, type 8MIM #615244
AR
113
ClinVar variants
26
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— ARHGDIA
🧬
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.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 43 VUS of 113 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.87LOEUF
pLI 0.036
Z-score 1.86
OE 0.38 (0.19–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.20Z-score
OE missense 0.70 (0.58–0.83)
87 obs / 124.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.19–0.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.58–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.57
0≤1.21.6
LoF obs/exp: 4 / 10.5Missense obs/exp: 87 / 124.9Syn Z: -3.35

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic4
VUS43
Likely Benign37
Benign5
Conflicting2
22
Pathogenic
4
Likely Pathogenic
43
VUS
37
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
21
0
22
Likely Pathogenic
1
0
3
0
4
VUS
2
36
5
0
43
Likely Benign
1
6
7
23
37
Benign
0
1
4
0
5
Conflicting
—2
Total4444023113

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Nephrotic syndrome, type 8

MIM #615244

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inactivation of RhoA for Hypertension Treatment Through the TRPV4-RhoA-RhoGDI1 Axis.
Wang J et al.·Circulation
2025
Loss of ARHGDIA expression is associated with poor prognosis in HCC and promotes invasion and metastasis of HCC cells.
Liang L et al.·Int J Oncol
2014
ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling.
Gee HY et al.·J Clin Invest
2013
ARHGDIA Confers Selective Advantage to Dissociated Human Pluripotent Stem Cells.
Riggs MJ et al.·Stem Cells Dev
2021
Genes associated with prognosis after surgery for malignant pleural mesothelioma promote tumor cell survival in vitro.
Gordon GJ et al.·BMC Cancer
2011
Personalized Comments on Challenges and Opportunities in Kidney Disease Therapeutics: The Glom-NExT Symposium.
Greka A et al.·Semin Nephrol
2016
Rare heterozygous variants in paediatric steroid resistant nephrotic syndrome - a population-based analysis of their significance.
Platt CJ et al.·Sci Rep
2024
Whole exome sequencing reveals novel candidate gene variants for MODY.
Yalçın Çapan Ö et al.·Clin Chim Acta
2020
KANK deficiency leads to podocyte dysfunction and nephrotic syndrome.
Gee HY et al.·J Clin Invest
2015
Four-gene expression ratio test for survival in patients undergoing surgery for mesothelioma.
Gordon GJ et al.·J Natl Cancer Inst
2009Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools