RRAGD

Chr 6AD

Ras related GTP binding D

Also known as: HOMG7, RAGD, bA11D8.2.1

NCBI Gene: 58528ENSG00000025039UniProt: Q9NQL2

RRAGD is a monomeric guanine nucleotide-binding protein, or G protein. By binding GTP or GDP, small G proteins act as molecular switches in numerous cell processes and signaling pathways.[supplied by OMIM, Apr 2004]

Primary Disease Associations & Inheritance

Hypomagnesemia 7, renal, with or without dilated cardiomyopathyMIM #620152
AD
70
ClinVar variants
21
Pathogenic / LP
0.82
pLI score
0
Active trials
Clinical Summary— RRAGD
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 47 VUS of 70 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.44LOEUF
pLI 0.820
Z-score 3.03
OE 0.14 (0.06–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.20Z-score
OE missense 0.57 (0.49–0.67)
119 obs / 208.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.14 (0.06–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.49–0.67)
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.0.84
0≤1.21.6
LoF obs/exp: 2 / 14.4Missense obs/exp: 119 / 208.2Syn Z: 1.13

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic2
VUS47
Likely Benign1
Conflicting1
19
Pathogenic
2
Likely Pathogenic
47
VUS
1
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
6
13
0
19
Likely Pathogenic
0
2
0
0
2
VUS
1
34
12
0
47
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Conflicting
—1
Total14226070

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

View in ClinVar →

Protein Context — Lollipop Plot

RRAGD · 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

Hypomagnesemia 7, renal, with or without dilated cardiomyopathy

MIM #620152

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RRAGD-Associated Autosomal Dominant Kidney Hypomagnesemia with Cardiomyopathy: A Review on the Clinical Manifestations and Therapeutic Options.
Trepiccione F et al.·Kidney Blood Press Res
2024Review
mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy.
Schlingmann KP et al.·J Am Soc Nephrol
2021
A prognostic glycolysis-related gene signature in osteosarcoma: implications for metabolic programming, immune microenvironment, and drug response.
Zhu N et al.·PeerJ
2025
Diagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases.
Wilke MVMB et al.·Orphanet J Rare Dis
2024Cohort
Dilated Cardiomyopathy With Concomitant Salt-Losing Renal Tubulopathy Caused by Heterozygous RRAGD Gene Variant.
de Frutos F et al.·Circ Genom Precis Med
2024Case report
System analysis of VEGFA in renal cell carcinoma: The expression, prognosis, gene regulation network and regulation targets.
Situ Y et al.·Int J Biol Markers
2022
Butyrate-Mediated Upregulation of Insulin Pathway Gene Expression Suggests Potential Antidiabetic Effects.
Shapira E et al.·Drug Dev Res
2025
Variants in ZNF365 isoform D are associated with Crohn's disease.
Haritunians T et al.·Gut
2011
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