Hypomagnesemia 7, renal, with or without dilated cardiomyopathy

Summary

Hypomagnesemia 7, renal, with or without dilated cardiomyopathy (MONDO:0859328) is a disease caused by RRAGD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RRAGD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypomagnesemia 7, renal, with or without dilated cardiomyopathy
Mondo ID	MONDO:0859328
OMIM	620152
DOID	DOID:0060972
UMLS	C5774266
MedGen	1824039
GARD	0026701
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn metal metabolism disorder › familial primary hypomagnesemia › hypomagnesemia 7, renal, with or without dilated cardiomyopathy

Related subtypes (4): familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis, familial primary hypomagnesemia with hypocalcuria, familial primary hypomagnesemia with normocalcuria, EGF-related primary hypomagnesemia with intellectual disability

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3765496	NM_021244.5(RRAGD):c.230C>T (p.Ser77Phe)	RRAGD	Pathogenic	no assertion criteria provided
3765497	NM_021244.5(RRAGD):c.272C>T (p.Thr91Ile)	RRAGD	Pathogenic	no assertion criteria provided
2692333	NM_021244.5(RRAGD):c.299T>G (p.Ile100Arg)	LOC129996828	Likely pathogenic	criteria provided, single submitter
1802633	NM_021244.5(RRAGD):c.227C>T (p.Ser76Leu)	RRAGD	Likely pathogenic	criteria provided, single submitter
4277978	NM_021244.5(RRAGD):c.643A>G (p.Ser215Gly)	RRAGD	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RRAGD	Strong	Autosomal dominant	hypomagnesemia 7, renal, with or without dilated cardiomyopathy	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RRAGD	Orphanet:73224	Kidney tubulopathy-dilated cardiomyopathy syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RRAGD	HGNC:19903	ENSG00000025039	Q9NQL2	Ras-related GTP-binding protein D	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RRAGD	Ras-related GTP-binding protein D	Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RRAGD	Other/Unknown	no		Gtr1_RagA, P-loop_NTPase, RagC/D

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of tongue	1
parotid gland	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RRAGD	290	ubiquitous	marker	body of tongue, parotid gland, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RRAGD	1,187

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RRAGD	Q9NQL2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
mTORC1-mediated signalling	1	475.8×	0.016	RRAGD
Energy dependent regulation of mTOR by LKB1-AMPK	1	393.8×	0.016	RRAGD
MTOR signalling	1	265.6×	0.016	RRAGD
PTEN Regulation	1	228.4×	0.016	RRAGD
Amino acids regulate mTORC1	1	200.3×	0.016	RRAGD
Regulation of PTEN gene transcription	1	178.4×	0.016	RRAGD
Cellular response to starvation	1	165.5×	0.016	RRAGD
Autophagy	1	148.3×	0.016	RRAGD
TP53 Regulates Metabolic Genes	1	129.8×	0.016	RRAGD
Macroautophagy	1	115.3×	0.016	RRAGD
Intracellular signaling by second messengers	1	91.4×	0.019	RRAGD
PIP3 activates AKT signaling	1	66.8×	0.024	RRAGD
Transcriptional Regulation by TP53	1	62.1×	0.024	RRAGD
Cellular responses to stress	1	36.8×	0.037	RRAGD
Cellular responses to stimuli	1	31.5×	0.040	RRAGD
RNA Polymerase II Transcription	1	22.5×	0.053	RRAGD
Gene expression (Transcription)	1	17.8×	0.063	RRAGD
Generic Transcription Pathway	1	15.1×	0.070	RRAGD
Signal Transduction	1	10.2×	0.098	RRAGD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to L-leucine	1	1404.3×	0.003	RRAGD
cellular response to leucine starvation	1	1404.3×	0.003	RRAGD
positive regulation of TOR signaling	1	495.6×	0.005	RRAGD
cellular response to amino acid stimulus	1	306.4×	0.005	RRAGD
positive regulation of TORC1 signaling	1	295.6×	0.005	RRAGD
negative regulation of autophagy	1	259.3×	0.005	RRAGD
cellular response to starvation	1	193.7×	0.006	RRAGD
intracellular protein localization	1	104.7×	0.010	RRAGD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RRAGD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RRAGD

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RRAGD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.