Intellectual developmental disorder 59

Summary

Intellectual developmental disorder 59 (MONDO:0032795) is a disease caused by CAMK2G (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CAMK2G (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder 59
Mondo ID	MONDO:0032795
OMIM	618522
DOID	DOID:0061033
UMLS	C5193190
MedGen	1678593
GARD	0025746
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder 59 · MRD59

Data availability: 23 ClinVar variants · 5 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 developmental disorder 59

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 54, intellectual disability, autosomal dominant 55, with seizures, intellectual disability, autosomal dominant 56, intellectual developmental disorder 61, 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

23 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 5 benign, 4 likely pathogenic, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
39975	NM_001367534.1(CAMK2G):c.875G>C (p.Arg292Pro)	CAMK2G	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687297	NM_001367534.1(CAMK2G):c.969dup (p.Ala324fs)	CAMK2G	Likely pathogenic	criteria provided, single submitter
1710167	NM_001367534.1(CAMK2G):c.676A>G (p.Ile226Val)	CAMK2G	Likely pathogenic	no assertion criteria provided
3068000	NM_001367534.1(CAMK2G):c.1236T>A (p.Asp412Glu)	CAMK2G	Likely pathogenic	criteria provided, single submitter
4690251	NM_001367534.1(CAMK2G):c.173_174del (p.Leu58fs)	CAMK2G	Likely pathogenic	criteria provided, single submitter
1687265	NM_001367534.1(CAMK2G):c.868T>C (p.Cys290Arg)	CAMK2G	Uncertain significance	criteria provided, single submitter
2442141	NM_001367534.1(CAMK2G):c.1534+149C>A	CAMK2G	Uncertain significance	criteria provided, single submitter
3064548	NM_001367534.1(CAMK2G):c.1757C>T (p.Pro586Leu)	CAMK2G	Uncertain significance	criteria provided, single submitter
3234994	NM_001367534.1(CAMK2G):c.1256C>T (p.Pro419Leu)	CAMK2G	Uncertain significance	criteria provided, single submitter
3236153	NM_001367534.1(CAMK2G):c.83T>C (p.Val28Ala)	CAMK2G	Uncertain significance	criteria provided, single submitter
3391124	NM_001367534.1(CAMK2G):c.1568C>G (p.Thr523Ser)	CAMK2G	Uncertain significance	criteria provided, multiple submitters, no conflicts
3391335	NM_001367534.1(CAMK2G):c.994G>A (p.Gly332Ser)	CAMK2G	Uncertain significance	criteria provided, single submitter
3484466	NM_001367534.1(CAMK2G):c.1657C>T (p.Arg553Trp)	CAMK2G	Uncertain significance	criteria provided, multiple submitters, no conflicts
3778992	NM_001367534.1(CAMK2G):c.397G>A (p.Val133Ile)	CAMK2G	Uncertain significance	criteria provided, single submitter
4278014	NM_001367534.1(CAMK2G):c.1364-655G>C	CAMK2G	Uncertain significance	criteria provided, single submitter
4533220	NM_001367534.1(CAMK2G):c.1666A>G (p.Thr556Ala)	CAMK2G	Uncertain significance	criteria provided, single submitter
4819075	NM_001367534.1(CAMK2G):c.292C>G (p.Leu98Val)	CAMK2G	Uncertain significance	criteria provided, single submitter
1192574	NM_001367534.1(CAMK2G):c.696+102_696+103insA	CAMK2G	Benign	criteria provided, single submitter
1192575	NM_001367534.1(CAMK2G):c.696+49del	CAMK2G	Benign	criteria provided, single submitter
1192576	NM_001367534.1(CAMK2G):c.275+69A>G	CAMK2G	Benign	criteria provided, multiple submitters, no conflicts
1192577	NM_001367534.1(CAMK2G):c.161-110A>G	CAMK2G	Benign	criteria provided, multiple submitters, no conflicts
1192578	NM_001367534.1(CAMK2G):c.147G>A (p.Lys49=)	CAMK2G	Benign	criteria provided, multiple submitters, no conflicts
4086063	NM_001367534.1(CAMK2G):c.1534+266G>T	CAMK2G	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 0 · 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
CAMK2G	Strong	Autosomal dominant	intellectual developmental disorder 59	6

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
CAMK2G	HGNC:1463	ENSG00000148660	Q13555	Calcium/calmodulin-dependent protein kinase type II subunit gamma	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAMK2G	Calcium/calmodulin-dependent protein kinase type II subunit gamma	Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic sp…

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)
CAMK2G	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
frontal pole	1
postcentral gyrus	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CAMK2G	287	ubiquitous	marker	frontal pole, postcentral gyrus, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAMK2G	3,148

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CAMK2G	Q13555	2

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	CAMK2G
CaMK IV-mediated phosphorylation of CREB	1	1142.0×	0.008	CAMK2G
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1	878.5×	0.008	CAMK2G
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	761.3×	0.008	CAMK2G
Ras activation upon Ca2+ influx through NMDA receptor	1	571.0×	0.008	CAMK2G
Trafficking of AMPA receptors	1	543.8×	0.008	CAMK2G
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.008	CAMK2G
Negative regulation of NMDA receptor-mediated neuronal transmission	1	543.8×	0.008	CAMK2G
Long-term potentiation	1	475.8×	0.008	CAMK2G
Signaling by RAS mutants	1	423.0×	0.008	CAMK2G
Cellular response to heat stress	1	393.8×	0.008	CAMK2G
Calmodulin induced events	1	380.7×	0.008	CAMK2G
CaM pathway	1	380.7×	0.008	CAMK2G
Ca-dependent events	1	368.4×	0.008	CAMK2G
Regulation of MECP2 expression and activity	1	368.4×	0.008	CAMK2G
Phase 0 - rapid depolarisation	1	346.1×	0.008	CAMK2G
RAF activation	1	335.9×	0.008	CAMK2G
G-protein mediated events	1	326.3×	0.008	CAMK2G
DAG and IP3 signaling	1	317.2×	0.008	CAMK2G
HSF1-dependent transactivation	1	317.2×	0.008	CAMK2G
Transcriptional Regulation by MECP2	1	317.2×	0.008	CAMK2G
Signaling by RAF1 mutants	1	278.5×	0.008	CAMK2G
Opioid Signalling	1	265.6×	0.008	CAMK2G
PLC beta mediated events	1	265.6×	0.008	CAMK2G
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.008	CAMK2G
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.008	CAMK2G
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.008	CAMK2G
Signaling downstream of RAS mutants	1	253.8×	0.008	CAMK2G
Oncogenic MAPK signaling	1	248.3×	0.008	CAMK2G
Ion transport by P-type ATPases	1	207.6×	0.009	CAMK2G

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×	0.001	CAMK2G
regulation of calcium ion transport	1	802.5×	0.003	CAMK2G
regulation of neuronal synaptic plasticity	1	674.1×	0.003	CAMK2G
regulation of protein localization to plasma membrane	1	648.1×	0.003	CAMK2G
regulation of neuron projection development	1	432.1×	0.003	CAMK2G
insulin secretion	1	432.1×	0.003	CAMK2G
long-term synaptic potentiation	1	280.9×	0.005	CAMK2G
nervous system development	1	45.9×	0.025	CAMK2G
cell differentiation	1	29.1×	0.034	CAMK2G

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
CAMK2G	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CAMK2G	39	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	CAMK2G
FEDRATINIB	4	CAMK2G
RUXOLITINIB	4	CAMK2G
PALBOCICLIB	4	CAMK2G
BARICITINIB	4	CAMK2G
BOSUTINIB	4	CAMK2G
ABEMACICLIB	4	CAMK2G
GILTERITINIB	4	CAMK2G
RIBOCICLIB	4	CAMK2G
BRIGATINIB	4	CAMK2G
SUNITINIB	4	CAMK2G
MIDOSTAURIN	4	CAMK2G
GEFITINIB	4	CAMK2G
ENZASTAURIN	3	CAMK2G
CRENOLANIB	3	CAMK2G
LINIFANIB	3	CAMK2G
ALVOCIDIB	3	CAMK2G
DOVITINIB	3	CAMK2G
LESTAURTINIB	3	CAMK2G
RUBOXISTAURIN	3	CAMK2G
SU-014813	2	CAMK2G
CENISERTIB	2	CAMK2G
ILORASERTIB	2	CAMK2G
DECERNOTINIB	2	CAMK2G
BMS-690514	2	CAMK2G
LY-2090314	2	CAMK2G
RG-547	2	CAMK2G
R-406	2	CAMK2G
BI-2536	2	CAMK2G
SOTRASTAURIN	2	CAMK2G

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CAMK2G	291	Binding:290, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAMK2G	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
CAMK2G	291

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

30 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)
MOMELOTINIB	4	CAMK2G
FEDRATINIB	4	CAMK2G
RUXOLITINIB	4	CAMK2G
PALBOCICLIB	4	CAMK2G
BARICITINIB	4	CAMK2G
BOSUTINIB	4	CAMK2G
ABEMACICLIB	4	CAMK2G
GILTERITINIB	4	CAMK2G
RIBOCICLIB	4	CAMK2G
BRIGATINIB	4	CAMK2G
SUNITINIB	4	CAMK2G
MIDOSTAURIN	4	CAMK2G
GEFITINIB	4	CAMK2G
ENZASTAURIN	3	CAMK2G
CRENOLANIB	3	CAMK2G
LINIFANIB	3	CAMK2G
ALVOCIDIB	3	CAMK2G
DOVITINIB	3	CAMK2G
LESTAURTINIB	3	CAMK2G
RUBOXISTAURIN	3	CAMK2G
SU-014813	2	CAMK2G
CENISERTIB	2	CAMK2G
ILORASERTIB	2	CAMK2G
DECERNOTINIB	2	CAMK2G
BMS-690514	2	CAMK2G
LY-2090314	2	CAMK2G
RG-547	2	CAMK2G
R-406	2	CAMK2G
BI-2536	2	CAMK2G
SOTRASTAURIN	2	CAMK2G

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CAMK2G
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.