Intellectual disability, autosomal dominant 40

Summary

Intellectual disability, autosomal dominant 40 (MONDO:0014699) is a disease caused by variants in CAMK2B and CHAMP1, with 6 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal genes: CAMK2B (GenCC Definitive), CHAMP1 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 64

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		37	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 40
Mondo ID	MONDO:0014699
OMIM	616579
Orphanet	692193
DOID	DOID:0070070
UMLS	C5676894
MedGen	1810363
GARD	0013539
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 40 · autosomal dominant non-syndromic intellectual disability caused by mutation in CHAMP1 · CHAMP1 autosomal dominant non-syndromic intellectual disability · intellectual disability, autosomal dominant 40 · intellectual disability, autosomal dominant type 40 · mental retardation, autosomal dominant 40 · mental retardation, autosomal dominant type 40 · MRD40

Data availability: 64 ClinVar variants · 4 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 40

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 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, 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

64 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 20 pathogenic, 11 likely pathogenic, 4 conflicting classifications of pathogenicity, 1 not provided, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3765511	NC_000013.11:g.114236634_114326291del	CDC16	Pathogenic	no assertion criteria provided
1064505	NM_032436.4(CHAMP1):c.959dup (p.Pro320_Arg321insTer)	CHAMP1	Pathogenic	criteria provided, single submitter
1065455	NM_032436.4(CHAMP1):c.647_649dup (p.Ser217Ter)	CHAMP1	Pathogenic	criteria provided, single submitter
1164024	NM_032436.4(CHAMP1):c.1995dup (p.Ser666Ter)	CHAMP1	Pathogenic	no assertion criteria provided
1322073	NM_032436.4(CHAMP1):c.1692dup (p.Lys565fs)	CHAMP1	Pathogenic	criteria provided, single submitter
1338820	NM_032436.4(CHAMP1):c.1741del (p.Glu581fs)	CHAMP1	Pathogenic	criteria provided, single submitter
1686872	NM_032436.4(CHAMP1):c.1043G>A (p.Trp348Ter)	CHAMP1	Pathogenic	no assertion criteria provided
1686873	NM_032436.4(CHAMP1):c.1876_1877del (p.Ser626fs)	CHAMP1	Pathogenic	no assertion criteria provided
208414	NM_032436.4(CHAMP1):c.635del (p.Pro212fs)	CHAMP1	Pathogenic	criteria provided, single submitter
208415	NM_032436.4(CHAMP1):c.1192C>T (p.Arg398Ter)	CHAMP1	Pathogenic	criteria provided, multiple submitters, no conflicts
208416	NM_032436.4(CHAMP1):c.1768C>T (p.Gln590Ter)	CHAMP1	Pathogenic	criteria provided, single submitter
208417	NM_032436.4(CHAMP1):c.1866_1867del (p.Asp622fs)	CHAMP1	Pathogenic	criteria provided, single submitter
210049	NM_032436.4(CHAMP1):c.1002G>A (p.Trp334Ter)	CHAMP1	Pathogenic	no assertion criteria provided
210050	NM_032436.4(CHAMP1):c.1489C>T (p.Arg497Ter)	CHAMP1	Pathogenic	criteria provided, multiple submitters, no conflicts
217909	NM_032436.4(CHAMP1):c.542_543del (p.Ser181fs)	CHAMP1	Pathogenic	criteria provided, single submitter
2442350	NM_032436.4(CHAMP1):c.2068_2069del (p.Glu690fs)	CHAMP1	Pathogenic	criteria provided, single submitter
3233724	NM_032436.4(CHAMP1):c.2000_2001del (p.Lys667fs)	CHAMP1	Pathogenic	criteria provided, single submitter
4819158	NM_032436.4(CHAMP1):c.292C>T (p.Gln98Ter)	CHAMP1	Pathogenic	criteria provided, single submitter
981896	NM_032436.4(CHAMP1):c.1858A>T (p.Lys620Ter)	CHAMP1	Pathogenic	criteria provided, multiple submitters, no conflicts
997692	NM_032436.4(CHAMP1):c.530_532delinsTTT (p.Ser177_Lys178delinsPheTer)	CHAMP1	Pathogenic	no assertion criteria provided
1687482	NM_032436.4(CHAMP1):c.824_828del (p.Thr274_Ser275insTer)	CHAMP1	Likely pathogenic	criteria provided, single submitter
1709765	NM_032436.4(CHAMP1):c.575_576del (p.Pro192fs)	CHAMP1	Likely pathogenic	criteria provided, single submitter
2444101	NM_032436.4(CHAMP1):c.2004_2005del (p.Asn669fs)	CHAMP1	Likely pathogenic	criteria provided, single submitter
2572392	NM_032436.4(CHAMP1):c.1440G>A (p.Trp480Ter)	CHAMP1	Likely pathogenic	criteria provided, single submitter
2663767	NM_032436.4(CHAMP1):c.1903_1906del (p.Glu635fs)	CHAMP1	Likely pathogenic	criteria provided, single submitter
3024272	NM_032436.4(CHAMP1):c.343C>T (p.Gln115Ter)	CHAMP1	Likely pathogenic	criteria provided, single submitter
3062279	NM_032436.4(CHAMP1):c.2027dup (p.Glu677fs)	CHAMP1	Likely pathogenic	criteria provided, single submitter
4294452	NM_032436.4(CHAMP1):c.1140G>A (p.Trp380Ter)	CHAMP1	Likely pathogenic	criteria provided, single submitter
4813317	NM_032436.4(CHAMP1):c.2081_2082del (p.Ile693_Ser694insTer)	CHAMP1	Likely pathogenic	criteria provided, single submitter
4813320	NM_032436.4(CHAMP1):c.2062dup (p.Glu688fs)	CHAMP1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 5 · 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
CHAMP1	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
CHAMP1	Orphanet:692193	CHAMP1-related intellectual disability-facial dysmorphism-behavioral abnormalities syndrome
SRC	Orphanet:480851	Hereditary thrombocytopenia with early-onset myelofibrosis
TRIO	Orphanet:476126	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
KMT2E	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

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
CHAMP1	HGNC:20311	ENSG00000198824	Q96JM3	Chromosome alignment-maintaining phosphoprotein 1	gencc,clinvar
SRC	HGNC:11283	ENSG00000197122	P12931	Proto-oncogene tyrosine-protein kinase Src	clinvar
TRIO	HGNC:12303	ENSG00000038382	O75962	Triple functional domain protein	clinvar
CDC16	HGNC:1720	ENSG00000130177	Q13042	Cell division cycle protein 16 homolog	clinvar
KMT2E	HGNC:18541	ENSG00000005483	Q8IZD2	Inactive histone-lysine N-methyltransferase 2E	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…
CHAMP1	Chromosome alignment-maintaining phosphoprotein 1	Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis.
SRC	Proto-oncogene tyrosine-protein kinase Src	Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G…
TRIO	Triple functional domain protein	Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases.
CDC16	Cell division cycle protein 16 homolog	Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
KMT2E	Inactive histone-lysine N-methyltransferase 2E	Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.5

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	3	13.9×	0.003
Transcription factor	2	2.8×	0.237
Other/Unknown	1	0.3×	0.993

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
CHAMP1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, CAMP
SRC	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TRIO	Kinase	yes		DH_dom, Prot_kinase_dom, CRAL-TRIO_dom
CDC16	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt
KMT2E	Transcription factor	no		SET_dom, Znf_PHD, Znf_FYVE_PHD

Expression context

Cohort genes with no expression data: 0.

5 cohort genes 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	2
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
ileal mucosa	1
secondary oocyte	1
body of stomach	1
gall bladder	1
rectum	1
stromal cell of endometrium	1
sural nerve	1
bronchial epithelial cell	1
epithelium of bronchus	1
right uterine tube	1
mucosa of paranasal sinus	1
tendon	1
tendon of biceps brachii	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
CHAMP1	244	ubiquitous	yes	ileal mucosa, cortical plate, secondary oocyte
SRC	236	ubiquitous	marker	body of stomach, gall bladder, rectum
TRIO	279	ubiquitous	marker	sural nerve, cortical plate, stromal cell of endometrium
CDC16	298	ubiquitous	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
KMT2E	264	ubiquitous	marker	tendon of biceps brachii, tendon, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRC	11,608
CDC16	3,185
TRIO	2,892
CAMK2B	2,679
KMT2E	2,340
CHAMP1	967

Structural data

PDB: 6 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SRC	P12931	79
CDC16	Q13042	21
CAMK2B	Q13554	4
CHAMP1	Q96JM3	4
TRIO	O75962	4
KMT2E	Q8IZD2	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 203. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DCC mediated attractive signaling	2	356.9×	0.002	SRC, TRIO
Long-term potentiation	2	237.9×	0.002	CAMK2B, SRC
Signaling by RAS mutants	2	211.5×	0.002	CAMK2B, SRC
RAF activation	2	167.9×	0.002	CAMK2B, SRC
Signaling by RAF1 mutants	2	139.3×	0.002	CAMK2B, SRC
Signaling by moderate kinase activity BRAF mutants	2	126.9×	0.002	CAMK2B, SRC
Paradoxical activation of RAF signaling by kinase inactive BRAF	2	126.9×	0.002	CAMK2B, SRC
Signaling downstream of RAS mutants	2	126.9×	0.002	CAMK2B, SRC
Oncogenic MAPK signaling	2	124.1×	0.002	CAMK2B, SRC
Post NMDA receptor activation events	2	102.0×	0.003	CAMK2B, SRC
Activation of NMDA receptors and postsynaptic events	2	92.1×	0.003	CAMK2B, SRC
Signaling by BRAF and RAF1 fusions	2	85.2×	0.003	CAMK2B, SRC
MAPK1/MAPK3 signaling	2	65.6×	0.005	CAMK2B, SRC
RNA Polymerase II Transcription	3	16.9×	0.005	CAMK2B, SRC, CDC16
MAPK family signaling cascades	2	51.4×	0.007	CAMK2B, SRC
Neurotransmitter receptors and postsynaptic signal transmission	2	50.1×	0.007	CAMK2B, SRC
Intracellular signaling by second messengers	2	45.7×	0.008	CAMK2B, SRC
Gene expression (Transcription)	3	13.4×	0.008	CAMK2B, SRC, CDC16
Regulation of gap junction activity	1	951.7×	0.011	SRC
Transmission across Chemical Synapses	2	38.1×	0.011	CAMK2B, SRC
Generic Transcription Pathway	3	11.3×	0.011	CAMK2B, SRC, CDC16
RAF/MAP kinase cascade	2	30.5×	0.014	CAMK2B, SRC
Disease	3	9.8×	0.015	CAMK2B, SRC, CDC16
Immune System	3	9.7×	0.015	CAMK2B, SRC, CDC16
Diseases of signal transduction by growth factor receptors and second messengers	2	28.4×	0.015	CAMK2B, SRC
Activated NTRK2 signals through FYN	1	475.8×	0.016	SRC
Activated NTRK3 signals through PI3K	1	475.8×	0.016	SRC
Signaling by NTRK2 (TRKB)	1	407.9×	0.018	SRC
CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde	1	356.9×	0.019	CAMK2B
Netrin mediated repulsion signals	1	317.2×	0.019	SRC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 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 caveolin-mediated endocytosis	1	2808.7×	0.016	SRC
regulation of skeletal muscle adaptation	1	1404.3×	0.016	CAMK2B
regulation of toll-like receptor 3 signaling pathway	1	1404.3×	0.016	SRC
positive regulation of dephosphorylation	1	1404.3×	0.016	SRC
sister chromatid biorientation	1	936.2×	0.016	CHAMP1
positive regulation of platelet-derived growth factor receptor-beta signaling pathway	1	936.2×	0.016	SRC
regulation of synapse structural plasticity	1	702.2×	0.016	CAMK2B
regulation of cell projection assembly	1	702.2×	0.016	SRC
regulation of epithelial cell migration	1	468.1×	0.016	SRC
negative regulation of telomere maintenance	1	468.1×	0.016	SRC
cellular response to progesterone stimulus	1	468.1×	0.016	SRC
negative regulation of neutrophil activation	1	401.2×	0.016	SRC
signal complex assembly	1	351.1×	0.016	SRC
cell surface receptor protein tyrosine phosphatase signaling pathway	1	351.1×	0.016	TRIO
osteoclast development	1	351.1×	0.016	SRC
positive regulation of small GTPase mediated signal transduction	1	351.1×	0.016	SRC
positive regulation of lamellipodium morphogenesis	1	351.1×	0.016	SRC
regulation of early endosome to late endosome transport	1	351.1×	0.016	SRC
regulation of intracellular estrogen receptor signaling pathway	1	312.1×	0.016	SRC
positive regulation of integrin activation	1	312.1×	0.016	SRC
ERBB2 signaling pathway	1	312.1×	0.016	SRC
negative regulation of mitochondrial depolarization	1	312.1×	0.016	SRC
positive regulation of podosome assembly	1	312.1×	0.016	SRC
positive regulation of synapse maturation	1	312.1×	0.016	CAMK2B
regulation of dendritic spine development	1	280.9×	0.016	CAMK2B
angiotensin-activated signaling pathway	1	255.3×	0.016	SRC
regulation of bone resorption	1	255.3×	0.016	SRC
intestinal epithelial cell development	1	255.3×	0.016	SRC
neutrophil mediated immunity	1	234.1×	0.016	KMT2E
protein localization to kinetochore	1	234.1×	0.016	CHAMP1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 3

Druggability breadth: 6 of 6 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
SRC	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRC	103	4
CAMK2B	25	4
CHAMP1	1	2
TRIO	0	0
CDC16	0	0
KMT2E	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	CAMK2B, SRC
SORAFENIB	4	CAMK2B, SRC
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B, SRC
MIDOSTAURIN	4	CAMK2B, SRC
PONATINIB	4	SRC
AFATINIB	4	SRC
TIVOZANIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	SRC
DASATINIB	4	SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
SRC	1,917	Binding:1858, Functional:43, ADMET:16
CAMK2B	314	Binding:313, Functional:1
CHAMP1	6	Binding:6
TRIO	2	Binding:2
CDC16	1	Binding:1
KMT2E	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAMK2B	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
SRC	2.7.10.2	non-specific protein-tyrosine 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
SRC	1,917

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
FEDRATINIB	4	CAMK2B, SRC
SORAFENIB	4	CAMK2B, SRC
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B, SRC
MIDOSTAURIN	4	CAMK2B, SRC
PONATINIB	4	SRC
AFATINIB	4	SRC
TIVOZANIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	SRC
DASATINIB	4	SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CAMK2B, SRC
B	Phased (≥1) drug, not yet approved	1	CHAMP1
C	Druggable family + PDB, no drug	1	TRIO
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CDC16, KMT2E

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TRIO	2	—
CDC16	1	—
KMT2E	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.