15q11q13 microduplication syndrome

Summary

15q11q13 microduplication syndrome (MONDO:0012081) is a disease with 9 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 9
• ClinVar variants: 25
• Phenotypes (HPO): 19

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		30	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000722	Compulsive behaviors	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0007018	Attention deficit hyperactivity disorder	Very frequent (80-99%)
HP:0000717	Autism	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0002186	Apraxia	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000298	Mask-like facies	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	15q11q13 microduplication syndrome
Mondo ID	MONDO:0012081
OMIM	608636
Orphanet	238446
NCIT	C126692
SNOMED CT	719427001
UMLS	C2675336
MedGen	390767
GARD	0017172
Is cancer (heuristic)	no

Also known as: 15q11-q13 duplication syndrome · 15q11-q13 microduplication syndrome · 15q11q13 duplication syndrome · autism susceptibility 4 · dup(15)(q11q13) · Dup15q · trisomy 15q11-q13 · trisomy 15q11q13

Data availability: 25 ClinVar variants · 35 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal duplication › partial duplication of the long arm of chromosome 15 › 15q11q13 microduplication syndrome

Related subtypes (1): 15q overgrowth syndrome

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

25 retrieved; paginated sample, class counts are floors:

21 pathogenic, 2 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
236260	Single allele		Pathogenic	no assertion criteria provided
4820130	NC_000015.9:g.20000001_(28100000_30300000)dup		Pathogenic	criteria provided, single submitter
1703231	Single allele	APBA2	Pathogenic	criteria provided, single submitter
2574688	GRCh37/hg19 15q11.2-13.2(chr15:22770421-30386398)	APBA2	Pathogenic	no assertion criteria provided
3062003	GRCh38/hg38 15q11.2-13.3(chr15:22612582-32116118)	APBA2	Pathogenic	criteria provided, single submitter
3062004	GRCh38/hg38 15q11.2-13.1(chr15:22612582-29993699)	APBA2	Pathogenic	criteria provided, single submitter
625709	GRCh37/hg19 15q11.1-13.2(chr15:20190548-30300265)	APBA2	Pathogenic	criteria provided, single submitter
625714	GRCh37/hg19 15q11.2-13.3(chr15:22383299-32917689)	APBA2	Pathogenic	criteria provided, single submitter
625745	GRCh37/hg19 15q11.2-13.1(chr15:23810184-29213896)	APBA2	Pathogenic	criteria provided, single submitter
1703637	GRCh37/hg19 15q11.2-13.1(chr15:23620191-28545601)	ATP10A	Pathogenic	no assertion criteria provided
2506559	GRCh37/hg19 15q11.2-13.1(chr15:23684691-28566579)	ATP10A	Pathogenic	criteria provided, single submitter
4819225	Single allele	ATP10A	Pathogenic	criteria provided, single submitter
625715	GRCh37/hg19 15q11.2-13.1(chr15:22770994-28517432)	ATP10A	Pathogenic	criteria provided, single submitter
625746	GRCh37/hg19 15q11.2-13.1(chr15:23810397-28525505)	ATP10A	Pathogenic	criteria provided, single submitter
666599	Single allele	ATP10A	Pathogenic	criteria provided, single submitter
1707411	Single allele	CYFIP1	Pathogenic	no assertion criteria provided
625833	GRCh37/hg19 15q11.2-13.1(chr15:22816713-28530182)	GOLGA6L2	Pathogenic	criteria provided, single submitter
625710	GRCh37/hg19 15q11.1-13.1(chr15:20191652-28525310)	IPW	Pathogenic	criteria provided, single submitter
625712	GRCh37/hg19 15q11.2-13.3(chr15:22382860-32396457)	KLF13	Pathogenic	criteria provided, single submitter
3062005	GRCh38/hg38 15q11.2-13.1(chr15:22612582-28435882)x4	LOC132090298	Pathogenic	criteria provided, single submitter
1098669	NC_000015.10:g.22804175_30375696dup	SNORD115-4	Pathogenic	criteria provided, single submitter
3250355	NC_000015.10:g.(?22786657)(28299516_?)dup	ATP10A	Likely pathogenic	criteria provided, single submitter
4292194	NM_181552.4(CUX1):c.1961-1G>A	CUX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
386816	NM_015570.4(AUTS2):c.3169G>A (p.Gly1057Ser)	AUTS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1341875	NC_000015.10:g.31722025_32224686dup	CHRNA7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP10A	Orphanet:411515	Angelman syndrome due to imprinting defect in 15q11-q13
AUTS2	Orphanet:352490	Autism spectrum disorder due to AUTS2 deficiency
AUTS2	Orphanet:641372	B-lymphoblastic leukemia/lymphoma with t(7;9)(q11.2;p13.2)
CHRNA7	Orphanet:199318	15q13.3 microdeletion syndrome
CUX1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

Cohort genes → proteins

9 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATP10A	HGNC:13542	ENSG00000206190	O60312	Phospholipid-transporting ATPase VA	clinvar
KLF13	HGNC:13672	ENSG00000169926	Q9Y2Y9	Krueppel-like factor 13	clinvar
CYFIP1	HGNC:13759	ENSG00000273749	Q7L576	Cytoplasmic FMR1-interacting protein 1	clinvar
AUTS2	HGNC:14262	ENSG00000158321	Q8WXX7	Autism susceptibility gene 2 protein	clinvar
CHRNA7	HGNC:1960	ENSG00000175344	P36544	Neuronal acetylcholine receptor subunit alpha-7	clinvar
CUX1	HGNC:2557	ENSG00000257923	P39880	Homeobox protein cut-like 1	clinvar
GOLGA6L2	HGNC:26695	ENSG00000174450	Q8N9W4	Golgin subfamily A member 6-like protein 2	clinvar
SNORD115-4	HGNC:33023	ENSG00000200680		small nucleolar RNA, C/D box 115-4	clinvar
APBA2	HGNC:579	ENSG00000034053	Q99767	Amyloid-beta A4 precursor protein-binding family A member 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP10A	Phospholipid-transporting ATPase VA	Catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane.
KLF13	Krueppel-like factor 13	Transcription factor that activates expression from GC-rich minimal promoter regions, including genes in the cells of the erythroid lineage.
CYFIP1	Cytoplasmic FMR1-interacting protein 1	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression.
AUTS2	Autism susceptibility gene 2 protein	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
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…
CUX1	Homeobox protein cut-like 1	Transcription factor involved in the control of neuronal differentiation in the brain.
APBA2	Amyloid-beta A4 precursor protein-binding family A member 2	Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery.

Protein-family classification

Druggable: 0 · Difficult: 4 · Unknown: 5 · Druggable fraction: 0.0

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
Transcription factor	3	2.8×	0.255
Scaffold/PPI	1	1.9×	0.623
Other/Unknown	5	1.0×	0.641

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP10A	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
KLF13	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
CYFIP1	Other/Unknown	no		Cytoplasmic_FMR1-int, CYRIA/CYRIB_Rac1-bd
AUTS2	Other/Unknown	no		AUTS2
CHRNA7	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
CUX1	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
GOLGA6L2	Other/Unknown	no		GOLGA6L
SNORD115-4	Other/Unknown	no
APBA2	Scaffold/PPI	no		PDZ, PTB/PI_dom, PH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

8 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)	1
broad (>20)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right hemisphere of cerebellum	2
oocyte	2
descending thoracic aorta	1
endothelial cell	1
thoracic aorta	1
cerebellar cortex	1
cerebellar hemisphere	1
epithelium of esophagus	1
esophagus squamous epithelium	1
germinal epithelium of ovary	1
cortical plate	1
ganglionic eminence	1
tibia	1
adrenal tissue	1
male germ line stem cell (sensu Vertebrata) in testis	1
buccal mucosa cell	1
secondary oocyte	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP10A	229	broad	marker	endothelial cell, descending thoracic aorta, thoracic aorta
KLF13	169	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CYFIP1	295	ubiquitous	marker	esophagus squamous epithelium, germinal epithelium of ovary, epithelium of esophagus
AUTS2	292	ubiquitous	marker	cortical plate, tibia, ganglionic eminence
CHRNA7	186	broad	marker	adrenal tissue, male germ line stem cell (sensu Vertebrata) in testis, oocyte
CUX1	297	ubiquitous	marker	secondary oocyte, buccal mucosa cell, oocyte
GOLGA6L2	18	tissue_specific	marker	left testis, right testis, testis
SNORD115-4	53		yes	adult mammalian kidney, skin of leg, liver
APBA2	131	ubiquitous	marker	superior frontal gyrus, right hemisphere of cerebellum, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CUX1	2,356
APBA2	2,193
CYFIP1	2,156
AUTS2	1,700
KLF13	1,019
ATP10A	1,016
CHRNA7	568
GOLGA6L2	430
SNORD115-4	0

Structural data

PDB: 3 · AlphaFold-only: 5 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHRNA7	P36544	51
CYFIP1	Q7L576	5
CUX1	P39880	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP10A	O60312	71.30
GOLGA6L2	Q8N9W4	62.54
APBA2	Q99767	59.74
KLF13	Q9Y2Y9	58.91
AUTS2	Q8WXX7	41.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 9 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	148.3×	0.070	CHRNA7
Acetylcholine binding and downstream events	1	116.5×	0.070	CHRNA7
Postsynaptic nicotinic acetylcholine receptors	1	116.5×	0.070	CHRNA7
Signaling by cytosolic FGFR1 fusion mutants	1	90.6×	0.070	CUX1
Neuronal System	2	12.7×	0.070	CHRNA7, APBA2
RHO GTPases Activate WASPs and WAVEs	1	45.3×	0.085	CYFIP1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	42.9×	0.085	AUTS2
Signaling by FGFR1 in disease	1	41.8×	0.085	CUX1
Protein-protein interactions at synapses	1	37.9×	0.085	APBA2
Intra-Golgi traffic	1	37.1×	0.085	CUX1
Ion transport by P-type ATPases	1	29.7×	0.085	ATP10A
Neurexins and neuroligins	1	28.1×	0.085	APBA2
FCGR3A-mediated phagocytosis	1	26.7×	0.085	CYFIP1
Regulation of actin dynamics for phagocytic cup formation	1	26.3×	0.085	CYFIP1
RHOG GTPase cycle	1	21.2×	0.087	CYFIP1
Transcriptional regulation by RUNX1	1	20.9×	0.087	AUTS2
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	20.9×	0.087	KLF13
VEGFA-VEGFR2 Pathway	1	19.9×	0.087	CYFIP1
RAC2 GTPase cycle	1	18.1×	0.091	CYFIP1
RAC3 GTPase cycle	1	17.0×	0.092	CYFIP1
Intra-Golgi and retrograde Golgi-to-ER traffic	1	15.0×	0.098	CUX1
Neurotransmitter receptors and postsynaptic signal transmission	1	14.3×	0.098	CHRNA7
Ion channel transport	1	13.7×	0.098	ATP10A
Transmission across Chemical Synapses	1	10.9×	0.118	CHRNA7
RAC1 GTPase cycle	1	8.7×	0.140	CYFIP1
Membrane Trafficking	1	5.3×	0.214	CUX1
Vesicle-mediated transport	1	5.0×	0.219	CUX1
Transport of small molecules	1	3.6×	0.283	ATP10A
Neutrophil degranulation	1	3.3×	0.291	CYFIP1
RNA Polymerase II Transcription	1	3.2×	0.291	AUTS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
dendrite extension	2	481.5×	5e-04	CYFIP1, AUTS2
positive regulation of lamellipodium assembly	2	172.0×	0.002	CYFIP1, AUTS2
axon extension	2	141.6×	0.002	CYFIP1, AUTS2
cognition	2	81.6×	0.005	CYFIP1, CHRNA7
monoatomic ion transmembrane transport	2	59.4×	0.007	ATP10A, CHRNA7
regulation of amyloid fibril formation	1	1203.7×	0.010	CHRNA7
sensory processing	1	802.5×	0.010	CHRNA7
regulation of translation at postsynapse, modulating synaptic transmission	1	802.5×	0.010	CYFIP1
positive regulation of membrane tubulation	1	802.5×	0.010	ATP10A
regulation of cell shape	2	35.1×	0.010	ATP10A, CYFIP1
synaptic transmission involved in micturition	1	601.9×	0.010	CHRNA7
dendritic spine organization	1	601.9×	0.010	CHRNA7
positive regulation of neurotrophin TRK receptor signaling pathway	1	481.5×	0.011	CYFIP1
regulation of amyloid precursor protein catabolic process	1	481.5×	0.011	CHRNA7
regulation of modification of postsynaptic actin cytoskeleton	1	343.9×	0.013	CYFIP1
modulation of excitatory postsynaptic potential	1	300.9×	0.013	CHRNA7
response to acetylcholine	1	300.9×	0.013	CHRNA7
positive regulation of Arp2/3 complex-mediated actin nucleation	1	300.9×	0.013	CYFIP1
chemical synaptic transmission	2	22.1×	0.013	CHRNA7, APBA2
dendrite arborization	1	267.5×	0.013	CHRNA7
negative regulation of erythrocyte differentiation	1	218.9×	0.016	KLF13
short-term memory	1	185.2×	0.017	CHRNA7
ruffle organization	1	185.2×	0.017	CYFIP1
positive regulation of protein metabolic process	1	141.6×	0.020	CHRNA7
response to amyloid-beta	1	141.6×	0.020	CHRNA7
positive regulation of dendrite morphogenesis	1	126.7×	0.020	CUX1
positive regulation of amyloid-beta formation	1	126.7×	0.020	CHRNA7
negative regulation of amyloid-beta formation	1	126.7×	0.020	CHRNA7
positive regulation of long-term synaptic potentiation	1	96.3×	0.025	CHRNA7
positive regulation of Rac protein signal transduction	1	92.6×	0.025	AUTS2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8

Druggability breadth: 2 of 9 evidence-associated genes (22%) 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
ATP10A	0	0
KLF13	0	0
CYFIP1	0	0
AUTS2	0	0
CUX1	0	0
GOLGA6L2	0	0
SNORD115-4	0	0
APBA2	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): 1.

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

Symbol	Assays	Type breakdown
CHRNA7	562	Binding:474, Functional:84, ADMET:3, Toxicity:1
CYFIP1	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP10A	7.6.2.1	P-type phospholipid transporter

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: 9; 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	0
E	Difficult family or no structure, no drug	8	ATP10A, KLF13, CYFIP1, AUTS2, CUX1, GOLGA6L2, SNORD115-4, APBA2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ATP10A	0	—
KLF13	0	—
CYFIP1	7	—
AUTS2	0	—
CUX1	0	—
GOLGA6L2	0	—
SNORD115-4	0	—
APBA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.