Intellectual disability, autosomal dominant

Summary

Intellectual disability, autosomal dominant (MONDO:0100172) is a disease (an umbrella term covering 29 Mondo subtypes) with 6 cohort genes.

At a glance

• Umbrella term: 29 Mondo subtypes
• Cohort genes: 6
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant
Mondo ID	MONDO:0100172
OMIM	156200
Is cancer (heuristic)	no

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

Data availability: 8 ClinVar variants.

Disease family

An umbrella term covering 29 Mondo subtypes.

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

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (29): 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 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

8 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 likely benign, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
377394	NM_001040142.2(SCN2A):c.3697G>T (p.Glu1233Ter)	SCN2A	Pathogenic	no assertion criteria provided
402116	NM_021224.6(ZNF462):c.3787C>T (p.Arg1263Ter)	ZNF462	Pathogenic	no assertion criteria provided
402117	NM_021224.6(ZNF462):c.4263del (p.Glu1422fs)	ZNF462	Pathogenic	no assertion criteria provided
402118	NM_021224.6(ZNF462):c.2979_2980delinsA (p.Val994fs)	ZNF462	Pathogenic	criteria provided, single submitter
943776	NM_001378120.1(MBD5):c.103C>A (p.Leu35Ile)	MBD5	Uncertain significance	criteria provided, multiple submitters, no conflicts
377393	NM_003070.5(SMARCA2):c.2329C>G (p.Leu777Val)	SMARCA2	Uncertain significance	no assertion criteria provided
377388	NM_012330.4(KAT6B):c.3544G>A (p.Glu1182Lys)	KAT6B	Likely benign	no assertion criteria provided
377389	NM_003491.4(NAA10):c.583C>T (p.Arg195Cys)	NAA10	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 17 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN2A	Orphanet:140927	Self-limited neonatal-infantile epilepsy
SCN2A	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN2A	Orphanet:2131	Alternating hemiplegia of childhood
SCN2A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN2A	Orphanet:306	Self-limited infantile epilepsy
SCN2A	Orphanet:33069	Dravet syndrome
SCN2A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN2A	Orphanet:697160	Infantile epileptic spasms syndrome
SMARCA2	Orphanet:3051	Nicolaides-Baraitser syndrome
SMARCA2	Orphanet:637013	SMARCA2-related blepharophimosis-intellectual disability syndrome
KAT6B	Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type
KAT6B	Orphanet:85201	Genitopatellar syndrome
NAA10	Orphanet:276432	Ogden syndrome
NAA10	Orphanet:568	Microphthalmia, Lenz type
MBD5	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
MBD5	Orphanet:228402	2q23.1 microdeletion syndrome
ZNF462	Orphanet:502430	Weiss-Kruszka Syndrome

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
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	clinvar
SMARCA2	HGNC:11098	ENSG00000080503	P51531	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	clinvar
KAT6B	HGNC:17582	ENSG00000156650	Q8WYB5	Histone acetyltransferase KAT6B	clinvar
NAA10	HGNC:18704	ENSG00000102030	P41227	N-alpha-acetyltransferase 10	clinvar
MBD5	HGNC:20444	ENSG00000204406	Q9P267	Methyl-CpG-binding domain protein 5	clinvar
ZNF462	HGNC:21684	ENSG00000148143	Q96JM2	Zinc finger protein 462	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of excitable membranes.
SMARCA2	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
KAT6B	Histone acetyltransferase KAT6B	Histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
NAA10	N-alpha-acetyltransferase 10	Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity.
MBD5	Methyl-CpG-binding domain protein 5	Non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at ‘Lys-120’ (H2AK119ub1).
ZNF462	Zinc finger protein 462	Zinc finger nuclear factor involved in transcription by regulating chromatin structure and organization.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.33

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
Ion channel	1	18.6×	0.210
Transcription factor	2	2.8×	0.316
Enzyme (other)	1	2.0×	0.543
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SMARCA2	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
KAT6B	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
NAA10	Enzyme (other)	yes	2.3.1.255	GNAT_dom, Acyl_CoA_acyltransferase, Ard1-like
MBD5	Other/Unknown	no		PWWP_dom, Methyl_CpG_DNA-bd, DNA-bd_dom_sf
ZNF462	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger/UBP_domain

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
calcaneal tendon	2
cortical plate	2
sural nerve	2
Brodmann (1909) area 23	1
cerebellar vermis	1
middle temporal gyrus	1
colonic epithelium	1
ventricular zone	1
apex of heart	1
lower esophagus muscularis layer	1
right hemisphere of cerebellum	1
adrenal tissue	1
buccal mucosa cell	1
corpus callosum	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis
SMARCA2	301	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate
KAT6B	140	ubiquitous	yes	cortical plate, ventricular zone, sural nerve
NAA10	288	ubiquitous	marker	right hemisphere of cerebellum, apex of heart, lower esophagus muscularis layer
MBD5	243	ubiquitous	marker	calcaneal tendon, adrenal tissue, sural nerve
ZNF462	258	ubiquitous	marker	buccal mucosa cell, oviduct epithelium, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA2	4,237
SCN2A	2,810
NAA10	2,579
KAT6B	2,214
MBD5	1,640
ZNF462	1,141

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCA2	P51531	32
NAA10	P41227	12
SCN2A	Q99250	5
KAT6B	Q8WYB5	3
ZNF462	Q96JM2	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MBD5	Q9P267	43.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. 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
Chromatin organization	2	40.8×	0.019	SMARCA2, KAT6B
Chromatin modifying enzymes	2	36.1×	0.019	SMARCA2, KAT6B
Formation of the non-canonical BAF (ncBAF) complex	1	167.9×	0.039	SMARCA2
Formation of the canonical BAF (cBAF) complex	1	158.6×	0.039	SMARCA2
Formation of the polybromo-BAF (pBAF) complex	1	158.6×	0.039	SMARCA2
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	114.2×	0.039	SMARCA2
Interaction between L1 and Ankyrins	1	92.1×	0.039	SCN2A
Regulation of endogenous retroelements	1	92.1×	0.039	SMARCA2
Phase 0 - rapid depolarisation	1	86.5×	0.039	SCN2A
Sensory perception of taste	1	84.0×	0.039	SCN2A
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	75.1×	0.039	SMARCA2
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	69.6×	0.039	SCN2A
Regulation of MITF-M-dependent genes involved in pigmentation	1	66.4×	0.039	SMARCA2
MITF-M-dependent gene expression	1	45.3×	0.053	SMARCA2
RMTs methylate histone arginines	1	36.6×	0.053	SMARCA2
Transcriptional regulation by RUNX1	1	36.6×	0.053	SMARCA2
Deubiquitination	1	31.0×	0.053	MBD5
UCH proteinases	1	31.0×	0.053	MBD5
L1CAM interactions	1	30.1×	0.053	SCN2A
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	29.4×	0.053	SMARCA2
MITF-M-regulated melanocyte development	1	28.6×	0.053	SMARCA2
Developmental Biology	2	7.2×	0.053	SCN2A, SMARCA2
Cardiac conduction	1	27.2×	0.054	SCN2A
Sensory Perception	1	23.8×	0.059	SCN2A
HATs acetylate histones	1	19.8×	0.066	KAT6B
Muscle contraction	1	19.3×	0.066	SCN2A
Epigenetic regulation of gene expression	1	17.8×	0.069	SMARCA2
Axon guidance	1	11.3×	0.104	SCN2A
Nervous system development	1	10.7×	0.105	SCN2A
RNA Polymerase II Transcription	1	5.6×	0.188	SMARCA2

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
positive regulation of protein refolding	1	2808.7×	0.005	NAA10
negative regulation of maintenance of mitotic sister chromatid cohesion, centromeric	1	2808.7×	0.005	NAA10
nervous system development	3	23.0×	0.005	SCN2A, SMARCA2, MBD5
intrinsic apoptotic signaling pathway in response to osmotic stress	1	1404.3×	0.008	SCN2A
positive regulation of growth hormone receptor signaling pathway	1	936.2×	0.009	MBD5
regulation of developmental process	1	401.2×	0.018	KAT6B
regulation of hemopoiesis	1	255.3×	0.023	KAT6B
regulation of behavior	1	234.1×	0.023	MBD5
positive regulation of transcription by RNA polymerase II	3	7.4×	0.025	SMARCA2, KAT6B, ZNF462
cardiac muscle cell action potential involved in contraction	1	117.0×	0.033	SCN2A
regulation of G0 to G1 transition	1	112.3×	0.033	SMARCA2
regulation of multicellular organism growth	1	108.0×	0.033	MBD5
regulation of nucleotide-excision repair	1	100.3×	0.033	SMARCA2
regulation of mitotic metaphase/anaphase transition	1	82.6×	0.033	SMARCA2
neuronal action potential	1	80.2×	0.033	SCN2A
positive regulation of T cell differentiation	1	75.9×	0.033	SMARCA2
regulation of DNA-templated transcription	2	10.5×	0.033	SMARCA2, KAT6B
negative regulation of DNA-templated transcription	2	10.5×	0.033	SMARCA2, KAT6B
positive regulation of myoblast differentiation	1	61.1×	0.034	SMARCA2
positive regulation of stem cell population maintenance	1	57.3×	0.034	SMARCA2
positive regulation of double-strand break repair	1	57.3×	0.034	SMARCA2
positive regulation of DNA-templated transcription	2	9.3×	0.034	SMARCA2, KAT6B
regulation of G1/S transition of mitotic cell cycle	1	51.1×	0.036	SMARCA2
negative regulation of cell differentiation	1	47.6×	0.036	SMARCA2
sodium ion transport	1	45.3×	0.036	SCN2A
positive regulation of cell differentiation	1	44.6×	0.036	SMARCA2
heterochromatin formation	1	42.6×	0.036	SMARCA2
myelination	1	41.9×	0.036	SCN2A
sodium ion transmembrane transport	1	33.8×	0.043	SCN2A
neuron apoptotic process	1	30.9×	0.045	SCN2A

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
SCN2A	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
SMARCA2	2	2
KAT6B	0	0
NAA10	0	0
MBD5	0	0
ZNF462	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
SMARCA2	311	Binding:274, Functional:25, ADMET:12
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
KAT6B	22	Binding:20, Functional:2
NAA10	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT6B	2.3.1.48	histone acetyltransferase
NAA10	2.3.1.255, 2.3.1.258, 2.3.1.48	N-terminal amino-acid Nalpha-acetyltransferase NatA, N-terminal methionine Nalpha-acetyltransferase NatE, histone acetyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN2A	203
SMARCA2	311

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)
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN2A
B	Phased (≥1) drug, not yet approved	1	SMARCA2
C	Druggable family + PDB, no drug	1	NAA10
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	KAT6B, MBD5, ZNF462

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KAT6B	22	—
NAA10	2	—
MBD5	0	—
ZNF462	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.