Intellectual disability, autosomal dominant 54

Summary

Intellectual disability, autosomal dominant 54 (MONDO:0030920) is a disease caused by CAMK2B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CAMK2B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 56

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 54
Mondo ID	MONDO:0030920
OMIM	617799
DOID	DOID:0080230
UMLS	C4540484
MedGen	1614787
GARD	0016474
Is cancer (heuristic)	no

Also known as: autosomal dominant mental retardation 54 · intellectual disability, autosomal dominant 54 · mental retardation, autosomal dominant 54 · MRD54

Data availability: 56 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal dominant non-syndromic intellectual disability › intellectual disability, autosomal dominant 54

Related subtypes (25): intellectual disability, autosomal dominant 22, neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language, intellectual disability, autosomal dominant 33, intellectual disability, autosomal dominant 34, intellectual disability, autosomal dominant 41, intellectual disability, autosomal dominant 43, intellectual disability, autosomal dominant 58, intellectual disability, autosomal dominant 45, intellectual disability, autosomal dominant 46, intellectual disability, autosomal dominant 47, Clark-Baraitser syndrome, intellectual disability, autosomal dominant 50, intellectual disability, autosomal dominant 51, intellectual disability, autosomal dominant 52, intellectual disability, autosomal dominant 53, intellectual disability, autosomal dominant 55, with seizures, intellectual disability, autosomal dominant 56, intellectual developmental disorder 61, intellectual developmental disorder 59, intellectual developmental disorder 60 with seizures, intellectual developmental disorder 62, intellectual developmental disorder, autosomal dominant 63, with macrocephaly, Coffin-Siris syndrome 6, intellectual disability, autosomal dominant 57, intellectual developmental disorder, autosomal dominant 73

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

56 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 10 benign, 5 pathogenic, 4 benign/likely benign, 4 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
430920	NM_001220.5(CAMK2B):c.85C>T (p.Arg29Ter)	CAMK2B	Pathogenic	criteria provided, multiple submitters, no conflicts
430921	NM_001220.5(CAMK2B):c.328G>A (p.Glu110Lys)	CAMK2B	Pathogenic	criteria provided, multiple submitters, no conflicts
430922	NM_001220.5(CAMK2B):c.416C>T (p.Pro139Leu)	CAMK2B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430923	NM_001220.5(CAMK2B):c.709G>A (p.Glu237Lys)	CAMK2B	Pathogenic	criteria provided, multiple submitters, no conflicts
430925	NM_001220.5(CAMK2B):c.901A>G (p.Lys301Glu)	CAMK2B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560179	NM_001220.5(CAMK2B):c.638C>T (p.Pro213Leu)	CAMK2B	Pathogenic	criteria provided, single submitter
560180	NM_001220.5(CAMK2B):c.852A>T (p.Arg284Ser)	CAMK2B	Pathogenic	no assertion criteria provided
2506486	NM_001220.5(CAMK2B):c.601+1G>A	CAMK2B	Likely pathogenic	criteria provided, single submitter
4819025	NM_001220.5(CAMK2B):c.1834G>T (p.Glu612Ter)	CAMK2B	Likely pathogenic	criteria provided, single submitter
4849224	NM_001220.5(CAMK2B):c.596C>T (p.Ala199Val)	CAMK2B	Likely pathogenic	criteria provided, single submitter
1333822	NM_001220.5(CAMK2B):c.696+1G>A	CAMK2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1341754	NM_001220.5(CAMK2B):c.1399G>A (p.Glu467Lys)	CAMK2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805867	NM_001220.5(CAMK2B):c.863_864del (p.Val288fs)	CAMK2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2152027	NM_001220.5(CAMK2B):c.1991C>T (p.Pro664Leu)	CAMK2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1098706	NM_001220.5(CAMK2B):c.197G>A (p.Arg66His)	CAMK2B	Uncertain significance	criteria provided, single submitter
1310348	NM_001220.5(CAMK2B):c.1597+1G>A	CAMK2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1328551	NM_001220.5(CAMK2B):c.1343C>T (p.Pro448Leu)	CAMK2B	Uncertain significance	criteria provided, single submitter
1428749	NM_001220.5(CAMK2B):c.1825G>A (p.Val609Ile)	CAMK2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1687391	NM_001220.5(CAMK2B):c.23C>A (p.Thr8Asn)	CAMK2B	Uncertain significance	criteria provided, single submitter
1712280	NM_001220.5(CAMK2B):c.1573A>G (p.Ile525Val)	CAMK2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1804132	NM_001220.5(CAMK2B):c.342-2A>G	CAMK2B	Uncertain significance	criteria provided, single submitter
1805456	NM_001220.5(CAMK2B):c.1310del (p.Pro437fs)	CAMK2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1806231	NM_001220.5(CAMK2B):c.1837G>C (p.Asp613His)	CAMK2B	Uncertain significance	criteria provided, single submitter
2439703	NM_001220.5(CAMK2B):c.161-5C>G	CAMK2B	Uncertain significance	criteria provided, single submitter
2439704	NM_001220.5(CAMK2B):c.1639G>C (p.Glu547Gln)	CAMK2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2444364	NM_001220.5(CAMK2B):c.331G>C (p.Ala111Pro)	CAMK2B	Uncertain significance	criteria provided, single submitter
2664914	NM_001220.5(CAMK2B):c.1567C>T (p.Pro523Ser)	CAMK2B	Uncertain significance	criteria provided, single submitter
2691761	NM_001220.5(CAMK2B):c.903G>A (p.Lys301=)	CAMK2B	Uncertain significance	no assertion criteria provided
3376326	NM_001220.5(CAMK2B):c.1127C>T (p.Ala376Val)	CAMK2B	Uncertain significance	criteria provided, single submitter
3377652	NM_001220.5(CAMK2B):c.1840G>C (p.Ala614Pro)	CAMK2B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CAMK2B	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 40	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CAMK2B	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
CAMK2B	HGNC:1461	ENSG00000058404	Q13554	Calcium/calmodulin-dependent protein kinase type II subunit beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAMK2B	Calcium/calmodulin-dependent protein kinase type II subunit beta	Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic r…

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)
CAMK2B	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

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
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
CAMK2B	233	broad	marker	cerebellar cortex, cerebellar hemisphere, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAMK2B	2,679

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CAMK2B	Q13554	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 61. 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
CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde	1	1427.5×	0.008	CAMK2B
CaMK IV-mediated phosphorylation of CREB	1	1142.0×	0.008	CAMK2B
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1	878.5×	0.008	CAMK2B
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	761.3×	0.008	CAMK2B
Ras activation upon Ca2+ influx through NMDA receptor	1	571.0×	0.008	CAMK2B
Trafficking of AMPA receptors	1	543.8×	0.008	CAMK2B
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.008	CAMK2B
Negative regulation of NMDA receptor-mediated neuronal transmission	1	543.8×	0.008	CAMK2B
Long-term potentiation	1	475.8×	0.008	CAMK2B
Signaling by RAS mutants	1	423.0×	0.008	CAMK2B
Cellular response to heat stress	1	393.8×	0.008	CAMK2B
Calmodulin induced events	1	380.7×	0.008	CAMK2B
CaM pathway	1	380.7×	0.008	CAMK2B
Ca-dependent events	1	368.4×	0.008	CAMK2B
Regulation of MECP2 expression and activity	1	368.4×	0.008	CAMK2B
Phase 0 - rapid depolarisation	1	346.1×	0.008	CAMK2B
RAF activation	1	335.9×	0.008	CAMK2B
G-protein mediated events	1	326.3×	0.008	CAMK2B
DAG and IP3 signaling	1	317.2×	0.008	CAMK2B
HSF1-dependent transactivation	1	317.2×	0.008	CAMK2B
Transcriptional Regulation by MECP2	1	317.2×	0.008	CAMK2B
Signaling by RAF1 mutants	1	278.5×	0.008	CAMK2B
Opioid Signalling	1	265.6×	0.008	CAMK2B
PLC beta mediated events	1	265.6×	0.008	CAMK2B
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.008	CAMK2B
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.008	CAMK2B
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.008	CAMK2B
Signaling downstream of RAS mutants	1	253.8×	0.008	CAMK2B
Oncogenic MAPK signaling	1	248.3×	0.008	CAMK2B
Ion transport by P-type ATPases	1	207.6×	0.009	CAMK2B

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
regulation of skeletal muscle adaptation	1	8426.0×	0.002	CAMK2B
regulation of synapse structural plasticity	1	4213.0×	0.002	CAMK2B
positive regulation of synapse maturation	1	1872.4×	0.003	CAMK2B
regulation of dendritic spine development	1	1685.2×	0.003	CAMK2B
regulation of long-term neuronal synaptic plasticity	1	991.3×	0.003	CAMK2B
positive regulation of dendritic spine morphogenesis	1	887.0×	0.003	CAMK2B
regulation of calcium ion transport	1	802.5×	0.003	CAMK2B
regulation of neuronal synaptic plasticity	1	674.1×	0.003	CAMK2B
regulation of protein localization to plasma membrane	1	648.1×	0.003	CAMK2B
regulation of neuron migration	1	624.1×	0.003	CAMK2B
long-term synaptic potentiation	1	280.9×	0.006	CAMK2B
protein autophosphorylation	1	145.3×	0.010	CAMK2B
positive regulation of neuron projection development	1	137.0×	0.010	CAMK2B
protein phosphorylation	1	68.0×	0.018	CAMK2B
nervous system development	1	45.9×	0.025	CAMK2B
cell differentiation	1	29.1×	0.037	CAMK2B
signal transduction	1	16.1×	0.062	CAMK2B

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
CAMK2B	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CAMK2B	25	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	CAMK2B
SORAFENIB	4	CAMK2B
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B
MIDOSTAURIN	4	CAMK2B
ENZASTAURIN	3	CAMK2B
LINIFANIB	3	CAMK2B
ALVOCIDIB	3	CAMK2B
CEDIRANIB	3	CAMK2B
QUERCETIN	3	CAMK2B
LESTAURTINIB	3	CAMK2B
DORAMAPIMOD	2	CAMK2B
SU-014813	2	CAMK2B
CENISERTIB	2	CAMK2B
ILORASERTIB	2	CAMK2B
LY-2090314	2	CAMK2B
RG-547	2	CAMK2B
BI-2536	2	CAMK2B
SOTRASTAURIN	2	CAMK2B
GSK-461364	1	CAMK2B
ATUVECICLIB	1	CAMK2B
SNS-314	1	CAMK2B
CYC-116	1	CAMK2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CAMK2B	314	Binding:313, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAMK2B	2.7.11.17	Ca2+/calmodulin-dependent protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CAMK2B	314

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

25 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)
FEDRATINIB	4	CAMK2B
SORAFENIB	4	CAMK2B
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B
MIDOSTAURIN	4	CAMK2B
ENZASTAURIN	3	CAMK2B
LINIFANIB	3	CAMK2B
ALVOCIDIB	3	CAMK2B
CEDIRANIB	3	CAMK2B
QUERCETIN	3	CAMK2B
LESTAURTINIB	3	CAMK2B
DORAMAPIMOD	2	CAMK2B
SU-014813	2	CAMK2B
CENISERTIB	2	CAMK2B
ILORASERTIB	2	CAMK2B
LY-2090314	2	CAMK2B
RG-547	2	CAMK2B
BI-2536	2	CAMK2B
SOTRASTAURIN	2	CAMK2B
GSK-461364	1	CAMK2B
ATUVECICLIB	1	CAMK2B
SNS-314	1	CAMK2B
CYC-116	1	CAMK2B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CAMK2B
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.