Hypomagnesemia, seizures, and intellectual disability

Summary

Hypomagnesemia, seizures, and intellectual disability (MONDO:0014631) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypomagnesemia, seizures, and intellectual disability
Mondo ID	MONDO:0014631
OMIM	616418
GARD	0025007
Is cancer (heuristic)	no

Also known as: HOMGSMR · hypomagnesemia, seizures, and intellectual disability · hypomagnesemia, seizures, and mental retardation

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 › hypomagnesemia, seizures, and intellectual disability

Related subtypes (2): renal hypomagnesemia 4, renal hypomagnesemia 6

Subtypes (2): hypomagnesemia, seizures, and intellectual disability 1, hypomagnesemia, seizures, and intellectual disability 2

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
TRPM7	Strong	Autosomal dominant	familial primary hypomagnesemia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPM7	Orphanet:140957	Autosomal dominant macrothrombocytopenia
TRPM7	Orphanet:90020	Parkinson-dementia complex of Guam

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
TRPM7	HGNC:17994	ENSG00000092439	Q96QT4	Transient receptor potential cation channel subfamily M member 7	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPM7	Transient receptor potential cation channel subfamily M member 7	Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPM7	Kinase	yes		a-kinase_dom, Kinase-like_dom_sf, TRPM7_a-kinase_dom

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
calcaneal tendon	1
cardiac muscle of right atrium	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPM7	247	ubiquitous	marker	left ventricle myocardium, calcaneal tendon, cardiac muscle of right atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPM7	1,995

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRPM7	Q96QT4	69.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
TRP channels	1	407.9×	0.002	TRPM7

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
calcium-dependent cell-matrix adhesion	1	8426.0×	0.002	TRPM7
intracellular magnesium ion homeostasis	1	2808.7×	0.002	TRPM7
magnesium ion homeostasis	1	1872.4×	0.002	TRPM7
zinc ion transport	1	1532.0×	0.002	TRPM7
magnesium ion transport	1	1203.7×	0.002	TRPM7
necroptotic process	1	1053.2×	0.002	TRPM7
monoatomic cation transmembrane transport	1	624.1×	0.003	TRPM7
actomyosin structure organization	1	561.7×	0.003	TRPM7
protein homotetramerization	1	237.3×	0.006	TRPM7
calcium ion transmembrane transport	1	210.7×	0.006	TRPM7
calcium ion transport	1	181.2×	0.007	TRPM7
protein autophosphorylation	1	145.3×	0.007	TRPM7
protein phosphorylation	1	68.0×	0.015	TRPM7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRPM7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TRPM7	34	Binding:34

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	1	TRPM7
E	Difficult family or no structure, no drug	0

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)
TRPM7	34	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.