Renal hypomagnesemia 6

Summary

Renal hypomagnesemia 6 (MONDO:0013480) is a disease caused by CNNM2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CNNM2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 140

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	renal hypomagnesemia 6
Mondo ID	MONDO:0013480
OMIM	613882
DOID	DOID:0060884
UMLS	C3151295
MedGen	462645
GARD	0012155
Is cancer (heuristic)	no

Also known as: HOMG6 · hypomagnesemia 6, renal · renal hypomagnesemia type 6 · renal hypomagnesemia-6

Data availability: 140 ClinVar variants · 1 GenCC gene-disease record.

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 › familial primary hypomagnesemia with normocalcuria › familial primary hypomagnesemia with normocalciuria and normocalcemia › renal hypomagnesemia 6

Related subtypes (2): renal hypomagnesemia 4, hypomagnesemia, seizures, and 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

140 retrieved; paginated sample, class counts are floors:

83 uncertain significance, 23 benign, 11 benign/likely benign, 7 conflicting classifications of pathogenicity, 6 likely pathogenic, 5 likely benign, 5 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2578374	NM_017649.5(CNNM2):c.1291G>A (p.Glu431Lys)	CNNM2	Pathogenic	criteria provided, single submitter
2578375	NM_017649.5(CNNM2):c.1310G>A (p.Gly437Glu)	CNNM2	Pathogenic	criteria provided, single submitter
2578376	NM_017649.5(CNNM2):c.2384C>A (p.Ser795Ter)	CNNM2	Pathogenic	criteria provided, single submitter
30683	NM_017649.5(CNNM2):c.117del (p.Ile40fs)	CNNM2	Pathogenic	no assertion criteria provided
30684	NM_017649.5(CNNM2):c.1703C>T (p.Thr568Ile)	CNNM2	Pathogenic	no assertion criteria provided
1098410	NM_017649.5(CNNM2):c.1804C>T (p.Arg602Ter)	CNNM2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2578373	NM_017649.5(CNNM2):c.1003G>A (p.Asp335Asn)	CNNM2	Likely pathogenic	criteria provided, single submitter
3256765	NM_017649.5(CNNM2):c.2576G>A (p.Cys859Tyr)	CNNM2	Likely pathogenic	no assertion criteria provided
3590449	NM_017649.5(CNNM2):c.1764C>G (p.Tyr588Ter)	CNNM2	Likely pathogenic	criteria provided, single submitter
3590455	NM_017649.5(CNNM2):c.1862C>A (p.Ser621Ter)	CNNM2	Likely pathogenic	criteria provided, single submitter
4074742	NM_017649.5(CNNM2):c.52_55dup (p.Ala19fs)	CNNM2	Likely pathogenic	criteria provided, single submitter
1487188	NM_017649.5(CNNM2):c.237G>A (p.Leu79=)	CNNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2194751	NM_017649.5(CNNM2):c.433A>G (p.Ser145Gly)	CNNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
298640	NM_017649.5(CNNM2):c.801C>T (p.Cys267=)	CNNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
877907	NM_017649.5(CNNM2):c.2400G>A (p.Ser800=)	CNNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
879849	NM_017649.5(CNNM2):c.2190C>T (p.Thr730=)	CNNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
879850	NM_017649.5(CNNM2):c.2355G>C (p.Ser785=)	CNNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
879851	NM_017649.5(CNNM2):c.2385G>T (p.Ser795=)	CNNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1375331	NM_017649.5(CNNM2):c.118A>G (p.Ile40Val)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1395222	NM_017649.5(CNNM2):c.1528C>T (p.Pro510Ser)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1430577	NM_017649.5(CNNM2):c.47G>A (p.Gly16Glu)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1435157	NM_017649.5(CNNM2):c.2593G>A (p.Ala865Thr)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1473335	NM_017649.5(CNNM2):c.2625C>G (p.Ile875Met)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1694570	NM_017649.5(CNNM2):c.2519C>G (p.Thr840Arg)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2025946	NM_017649.5(CNNM2):c.1938G>T (p.Glu646Asp)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2178214	NM_017649.5(CNNM2):c.88C>T (p.Arg30Cys)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2280117	NM_017649.5(CNNM2):c.554A>G (p.Lys185Arg)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2282659	NM_017649.5(CNNM2):c.458G>A (p.Arg153His)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2296384	NM_017649.5(CNNM2):c.2594C>G (p.Ala865Gly)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2575702	NM_017649.5(CNNM2):c.2354C>T (p.Ser785Leu)	CNNM2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
CNNM2	Definitive	Semidominant	hypomagnesemia, seizures, and intellectual disability 1	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity 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
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.

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)
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll

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
oocyte	1
right adrenal gland	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNNM2	1,230

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNNM2	Q9H8M5	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
magnesium ion homeostasis	1	1872.4×	5e-04	CNNM2

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
CNNM2	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	CNNM2

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)
CNNM2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.