Chromosome 15q13.3 microdeletion syndrome

Summary

Chromosome 15q13.3 microdeletion syndrome (MONDO:0012774) is a disease with 4 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 14
• Phenotypes (HPO): 21

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		264	Worldwide	Validated
Point prevalence	1-9 / 100 000	2.5	Worldwide	Validated
Prevalence at birth	1-5 / 10 000	0.018	United States	Validated
Prevalence at birth	1-5 / 10 000	0.04	Norway	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000411	Protruding ear	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000995	Melanocytic nevus	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0005274	Prominent nasal tip	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0007302	Bipolar affective disorder	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)
HP:0100753	Schizophrenia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 15q13.3 microdeletion syndrome
Mondo ID	MONDO:0012774
MeSH	C567439
OMIM	612001
Orphanet	199318
DOID	DOID:0060394
SNOMED CT	699254009
UMLS	C2677613
MedGen	393784
GARD	0010296
Is cancer (heuristic)	no

Also known as: 15q13.3 microdeletion · 15q13.3 microdeletion syndrome · chromosome 15q13.3 microdeletion syndrome · Del(15)(q13.3) · microdeletion 15q13.3 syndrome · monosomy 15q13.3

Data availability: 14 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › chromosome 15q13.3 microdeletion syndrome

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

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

14 retrieved; paginated sample, class counts are floors:

12 pathogenic, 1 uncertain significance, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703668	GRCh37/hg19 15q13.2-13.3(chr15:31098690-32914240)	ARHGAP11A	Pathogenic	no assertion criteria provided
1330163	GRCh37/hg19 15q13.2-13.3(chr15:30897996-32404614)x1	ARHGAP11B	Pathogenic	criteria provided, single submitter
2446467	GRCh37/hg19 15q13.2-13.3(chr15:30921917-32514980)x1	ARHGAP11B	Pathogenic	no assertion criteria provided
2580300	GRCh37/hg19 15q13.2-13.3(chr15:30805785-32686484)x1	ARHGAP11B	Pathogenic	criteria provided, single submitter
2580303	GRCh37/hg19 15q13.2-13.3(chr15:30918974-32442006)x1	ARHGAP11B	Pathogenic	criteria provided, single submitter
2580323	GRCh37/hg19 15q13.2-13.3(chr15:30897996-32442006)x1	ARHGAP11B	Pathogenic	criteria provided, single submitter
2580334	GRCh37/hg19 15q13.2-13.3(chr15:30854238-32892694)x1	ARHGAP11B	Pathogenic	criteria provided, single submitter
1703648	GRCh37/hg19 15q13.2-13.3(chr15:31088442-32446830)	CHRNA7	Pathogenic	no assertion criteria provided
1703658	GRCh37/hg19 15q13.2-13.3(chr15:31073668-32446830)	CHRNA7	Pathogenic	no assertion criteria provided
2574687	GRCh37/hg19 15q13.2-13.3(chr15:31073735-32446830)	CHRNA7	Pathogenic	no assertion criteria provided
1703232	Single allele	LOC112272582	Pathogenic	criteria provided, single submitter
21009	15q13.3	MTMR10	Pathogenic	no assertion criteria provided
2672247	NM_000746.6(CHRNA7):c.992C>T (p.Thr331Ile)	CHRNA7	Uncertain significance	criteria provided, single submitter
441046	GRCh37/hg19 15q13.2-13.3(chr15:31108661-32446830)x1	MTMR10	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHRNA7	Orphanet:199318	15q13.3 microdeletion syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARHGAP11B	HGNC:15782	ENSG00000285077	Q3KRB8	Inactive Rho GTPase-activating protein 11B	clinvar
ARHGAP11A	HGNC:15783	ENSG00000198826	Q6P4F7	Rho GTPase-activating protein 11A	clinvar
CHRNA7	HGNC:1960	ENSG00000175344	P36544	Neuronal acetylcholine receptor subunit alpha-7	clinvar
MTMR10	HGNC:25999	ENSG00000166912	Q9NXD2	Myotubularin-related protein 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARHGAP11B	Inactive Rho GTPase-activating protein 11B	Hominin-specific protein that promotes development and evolutionary expansion of the brain neocortex.
ARHGAP11A	Rho GTPase-activating protein 11A	GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
CHRNA7	Neuronal acetylcholine receptor subunit alpha-7	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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
Phosphatase	1	21.0×	0.094
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARHGAP11B	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, ARHGAP11A/B
ARHGAP11A	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, ARHGAP11A/B
CHRNA7	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
MTMR10	Phosphatase	yes		Myotubularin-like_Pase_dom, PH-like_dom_sf, MTMR12-like_C

Expression context

Cohort genes with no expression data: 0.

2 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
bone marrow	1
bone marrow cell	1
ganglionic eminence	1
primordial germ cell in gonad	1
ventricular zone	1
adrenal tissue	1
oocyte	1
corpus callosum	1
inferior vagus X ganglion	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARHGAP11B	134	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, bone marrow, bone marrow cell
ARHGAP11A	134	ubiquitous	marker	ganglionic eminence, ventricular zone, primordial germ cell in gonad
CHRNA7	186	broad	marker	adrenal tissue, male germ line stem cell (sensu Vertebrata) in testis, oocyte
MTMR10	256	ubiquitous	yes	corpus callosum, inferior vagus X ganglion, spinal cord

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARHGAP11A	1,509
ARHGAP11B	975
MTMR10	784
CHRNA7	568

Intra-cohort edges

A	B	Sources
ARHGAP11B	MTMR10	string_interaction
CHRNA7	MTMR10	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHRNA7	P36544	51
ARHGAP11A	Q6P4F7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MTMR10	Q9NXD2	79.94
ARHGAP11B	Q3KRB8	77.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 4 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
RHOA GTPase cycle	2	37.3×	0.014	ARHGAP11B, ARHGAP11A
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	259.6×	0.015	CHRNA7
Acetylcholine binding and downstream events	1	203.9×	0.015	CHRNA7
Postsynaptic nicotinic acetylcholine receptors	1	203.9×	0.015	CHRNA7
Synthesis of PIPs at the early endosome membrane	1	178.4×	0.015	MTMR10
PI Metabolism	1	89.2×	0.024	MTMR10
Phospholipid metabolism	1	50.1×	0.037	MTMR10
Neurotransmitter receptors and postsynaptic signal transmission	1	25.0×	0.064	CHRNA7
Transmission across Chemical Synapses	1	19.0×	0.070	CHRNA7
CDC42 GTPase cycle	1	18.1×	0.070	ARHGAP11B
Neuronal System	1	11.1×	0.103	CHRNA7
Metabolism of lipids	1	7.9×	0.131	MTMR10
Metabolism	1	2.9×	0.302	MTMR10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of mitochondrial membrane permeability	1	2808.7×	0.004	ARHGAP11B
regulation of amyloid fibril formation	1	2808.7×	0.004	CHRNA7
L-glutamine catabolic process	1	1872.4×	0.004	ARHGAP11B
sensory processing	1	1872.4×	0.004	CHRNA7
synaptic transmission involved in micturition	1	1404.3×	0.004	CHRNA7
dendritic spine organization	1	1404.3×	0.004	CHRNA7
regulation of small GTPase mediated signal transduction	2	96.0×	0.004	ARHGAP11B, ARHGAP11A
signal transduction	3	16.1×	0.004	ARHGAP11B, ARHGAP11A, CHRNA7
regulation of amyloid precursor protein catabolic process	1	1123.5×	0.004	CHRNA7
modulation of excitatory postsynaptic potential	1	702.2×	0.005	CHRNA7
response to acetylcholine	1	702.2×	0.005	CHRNA7
dendrite arborization	1	624.1×	0.006	CHRNA7
short-term memory	1	432.1×	0.007	CHRNA7
positive regulation of protein metabolic process	1	330.4×	0.008	CHRNA7
response to amyloid-beta	1	330.4×	0.008	CHRNA7
positive regulation of amyloid-beta formation	1	295.6×	0.008	CHRNA7
negative regulation of amyloid-beta formation	1	295.6×	0.008	CHRNA7
positive regulation of long-term synaptic potentiation	1	224.7×	0.010	CHRNA7
acetylcholine receptor signaling pathway	1	208.1×	0.011	CHRNA7
positive regulation of excitatory postsynaptic potential	1	175.5×	0.012	CHRNA7
excitatory postsynaptic potential	1	147.8×	0.013	CHRNA7
response to nicotine	1	140.4×	0.013	CHRNA7
negative regulation of cytokine production involved in inflammatory response	1	140.4×	0.013	CHRNA7
cognition	1	95.2×	0.017	CHRNA7
synapse organization	1	93.6×	0.017	CHRNA7
positive regulation of GTPase activity	1	92.1×	0.017	ARHGAP11A
negative regulation of tumor necrosis factor production	1	83.8×	0.018	CHRNA7
learning or memory	1	80.2×	0.019	CHRNA7
regulation of membrane potential	1	77.0×	0.019	CHRNA7
monoatomic ion transmembrane transport	1	69.3×	0.020	CHRNA7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) 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
CHRNA7	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRNA7	30	4
ARHGAP11B	0	0
ARHGAP11A	0	0
MTMR10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARENICLINE	4	CHRNA7
NALTREXONE	4	CHRNA7
MECAMYLAMINE	4	CHRNA7
NICOTINE	4	CHRNA7
TROPISETRON	4	CHRNA7
ACETYLCHOLINE	4	CHRNA7
BUPROPION	4	CHRNA7
CARBAMOYLCHOLINE	4	CHRNA7
DEXMECAMYLAMINE	3	CHRNA7
ENCENICLINE	3	CHRNA7
CYTISINICLINE	3	CHRNA7
LEVOMENOL	2	CHRNA7
LOBELINE	2	CHRNA7
STILONIUM IODIDE	2	CHRNA7
BRADANICLINE	2	CHRNA7
RIVANICLINE	2	CHRNA7
GTS-21	2	CHRNA7
STILONIUM	2	CHRNA7
AZD0328	2	CHRNA7
FACINICLINE	2	CHRNA7
AZD1446	2	CHRNA7
TEBANICLINE	2	CHRNA7
TILORONE	2	CHRNA7
SSR180711	2	CHRNA7
PHA-543613	1	CHRNA7
ABT-107	1	CHRNA7
TRANSTORINE	1	CHRNA7
AVL-3288	1	CHRNA7
TC-2216	1	CHRNA7
NORNICOTINE	1	CHRNA7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CHRNA7	562	Binding:474, Functional:84, ADMET:3, Toxicity:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHRNA7	562

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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)
VARENICLINE	4	CHRNA7
NALTREXONE	4	CHRNA7
MECAMYLAMINE	4	CHRNA7
NICOTINE	4	CHRNA7
TROPISETRON	4	CHRNA7
ACETYLCHOLINE	4	CHRNA7
BUPROPION	4	CHRNA7
CARBAMOYLCHOLINE	4	CHRNA7
DEXMECAMYLAMINE	3	CHRNA7
ENCENICLINE	3	CHRNA7
CYTISINICLINE	3	CHRNA7
LEVOMENOL	2	CHRNA7
LOBELINE	2	CHRNA7
STILONIUM IODIDE	2	CHRNA7
BRADANICLINE	2	CHRNA7
RIVANICLINE	2	CHRNA7
GTS-21	2	CHRNA7
STILONIUM	2	CHRNA7
AZD0328	2	CHRNA7
FACINICLINE	2	CHRNA7
AZD1446	2	CHRNA7
TEBANICLINE	2	CHRNA7
TILORONE	2	CHRNA7
SSR180711	2	CHRNA7
PHA-543613	1	CHRNA7
ABT-107	1	CHRNA7
TRANSTORINE	1	CHRNA7
AVL-3288	1	CHRNA7
TC-2216	1	CHRNA7
NORNICOTINE	1	CHRNA7

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHRNA7
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	MTMR10
E	Difficult family or no structure, no drug	2	ARHGAP11B, ARHGAP11A

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)
ARHGAP11B	0	—
ARHGAP11A	0	—
MTMR10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.