Intellectual disability, autosomal dominant 10

Summary

Intellectual disability, autosomal dominant 10 (MONDO:0013657) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 10
Mondo ID	MONDO:0013657
OMIM	614256
DOID	DOID:0070040
UMLS	C3280284
MedGen	481914
GARD	0016460
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 10 · autosomal dominant non-syndromic intellectual disability caused by mutation in CACNG2 · CACNG2 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 10 · intellectual disability, autosomal dominant type 10 · mental retardation, autosomal dominant 10 · mental retardation, autosomal dominant type 10 · MRD10

Data availability: 11 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 › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual disability, autosomal dominant 10

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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

11 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 1 no classifications from unflagged records, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1679231	NM_006078.5(CACNG2):c.944C>G (p.Thr315Arg)	CACNG2	Uncertain significance	criteria provided, single submitter
1701665	NM_006078.5(CACNG2):c.669C>G (p.Ile223Met)	CACNG2	Uncertain significance	criteria provided, single submitter
2439696	NM_006078.5(CACNG2):c.136A>C (p.Ser46Arg)	CACNG2	Uncertain significance	criteria provided, single submitter
2533278	NM_006078.5(CACNG2):c.376G>A (p.Glu126Lys)	CACNG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582511	NM_006078.5(CACNG2):c.956G>C (p.Arg319Pro)	CACNG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2661916	NM_006078.5(CACNG2):c.589G>A (p.Ala197Thr)	CACNG2	Uncertain significance	criteria provided, single submitter
30282	NM_006078.5(CACNG2):c.427G>C (p.Val143Leu)	CACNG2	no classifications from unflagged records	no classifications from unflagged records
3896728	NM_006078.5(CACNG2):c.82_101del (p.Val28fs)	CACNG2	Uncertain significance	criteria provided, single submitter
931257	NM_006078.5(CACNG2):c.298G>T (p.Ala100Ser)	CACNG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
992728	NM_006078.5(CACNG2):c.859A>T (p.Thr287Ser)	CACNG2	Uncertain significance	criteria provided, single submitter
4819242	NM_006078.5(CACNG2):c.925G>A (p.Asp309Asn)	CACNG2	Likely benign	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
CACNG2	Supportive	Autosomal dominant	autosomal dominant non-syndromic intellectual disability	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CACNG2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
CACNG2	HGNC:1406	ENSG00000166862	Q9Y698	Voltage-dependent calcium channel gamma-2 subunit	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CACNG2	Voltage-dependent calcium channel gamma-2 subunit	Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs).

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)
CACNG2	Other/Unknown	no		PMP22/EMP/MP20/Claudin, VDCC_g2su, VDCC_gsu

Expression context

Cohort genes with no expression data: 0.

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CACNG2	70	tissue_specific	yes	right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CACNG2	1,380

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CACNG2	Q9Y698	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Presynaptic depolarization and calcium channel opening	1	951.7×	0.004	CACNG2
LGI-ADAM interactions	1	815.7×	0.004	CACNG2
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	761.3×	0.004	CACNG2
Trafficking of AMPA receptors	1	543.8×	0.004	CACNG2
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.016	CACNG2
Transmission across Chemical Synapses	1	76.1×	0.018	CACNG2
Neuronal System	1	44.3×	0.026	CACNG2
Developmental Biology	1	14.5×	0.069	CACNG2

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
eye blink reflex	1	16852.0×	4e-04	CACNG2
positive regulation of protein localization to basolateral plasma membrane	1	16852.0×	4e-04	CACNG2
postsynaptic neurotransmitter receptor diffusion trapping	1	2106.5×	0.001	CACNG2
membrane hyperpolarization	1	1872.4×	0.001	CACNG2
regulation of AMPA receptor activity	1	1685.2×	0.001	CACNG2
neurotransmitter receptor localization to postsynaptic specialization membrane	1	802.5×	0.002	CACNG2
transmission of nerve impulse	1	648.1×	0.002	CACNG2
positive regulation of synaptic transmission, glutamatergic	1	624.1×	0.002	CACNG2
neuromuscular junction development	1	526.6×	0.002	CACNG2
membrane depolarization	1	510.7×	0.002	CACNG2
response to calcium ion	1	318.0×	0.003	CACNG2
protein targeting to membrane	1	295.6×	0.003	CACNG2

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CACNG2	NIMODIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNG2	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIMODIPINE	4	CACNG2
TACRINE	4	CACNG2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CACNG2	17	Binding:15, ADMET:2

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
NIMODIPINE	4	CACNG2
TACRINE	4	CACNG2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CACNG2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.