Autism spectrum disorder

Summary

Autism spectrum disorder (MONDO:0005258) is a disease (an umbrella term covering 5 Mondo subtypes) caused by variants in DDX53 and GIGYF1, with 52 cohort genes (1,292 GWAS associations across 74 studies) and 1,517 clinical trials. The dominant Reactome pathway is Butyrophilin (BTN) family interactions (7 cohort genes). Top therapeutic interventions include cariprazine, buspirone, and bumetanide.

At a glance

• Causal genes: DDX53 (GenCC Strong), GIGYF1 (GenCC Strong)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 52
• GWAS associations: 1,292
• ClinVar variants: 730
• Clinical trials: 1,517

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autism spectrum disorder
Mondo ID	MONDO:0005258
EFO	EFO:0003756
Orphanet	106
DOID	DOID:0060041
ICD-11	437815624
NCIT	C88412
SNOMED CT	408856003
UMLS	C1510586
MedGen	307153
Is cancer (heuristic)	no

Also known as: autism spectrum disorder · autistic spectrum disorder · pervasive developmental disorder - not otherwise specified · pervasive developmental disorders

Data availability: 730 ClinVar variants · 1,292 GWAS associations (74 studies) · 42 GenCC gene-disease records · 302 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › pervasive developmental disorder › autism spectrum disorder

Related subtypes (4): Rett syndrome, childhood disintegrative disorder, atypical autism, FOXG1 disorder

Subtypes (5): autism, PAX5-related B lymphopenia and autism spectrum disorder, autism spectrum disorder 1, autism spectrum disorder 2, autism spectrum disorder 3

Genetics & variants

GWAS landscape

1,292 GWAS associations across 74 studies. Top hits map to 29 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2352974	7e-35	TRAIP	?
rs7623659	2e-31	RHOA	?
rs13217619	1e-27	ZSCAN31	?
rs11793831	1e-27	LINC03142	?
rs115329265	2e-27	RPSAP2 - NOP56P1	A	1.17
rs55838312	8e-27	TET2-AS1, TET2	?
rs116137698	3e-26	LINC00533	A	1.22
rs2008514	4e-26	PLA2G10KP - ATXN2L	?
rs141342723	4e-24	RPL8P1 - LINC01012	T	1.2
rs75782365	8e-24	BTN3A1	T	1.21
rs9384679	4e-23	AFG1L - FOXO3	?
rs151267808	1e-22	POLR1HASP, POLR1HASP	T	1.24
rs3128341	9e-22	LINC02796	?
rs7746199	1e-20	POM121L2	?	1.14
rs56150095	3e-20	CALN1	?
rs114115252	8e-20	SFTA2	?	1.16
rs4298967	8e-20	CACNA1C, CACNA1C-IT3	?
rs1782810	1e-19	MIR137HG	A	1.12
rs6921919	1e-19	ZKSCAN3	C	1.12
rs1486091	1e-19	NEGR1	?
rs9467711	3e-19	H3C9P - BTN3A2	A	1.16
rs28888764	4e-19	PLA2G10KP - ATXN2L	?
rs67981811	5e-19	ZSCAN12	C	8.91
rs115707823	6e-18	UBQLN1P1 - MICC	?	1.19
rs116633139	6e-18	HLA-DQB1 - MTCO3P1	?	1.16
rs10733389	6e-18	LINC03142	?
rs115123779	1e-17	LINC02829	?	1.15
rs7531118	1e-17	LINC02796	?
rs1054442	1e-17	DDN	?
rs2454205	1e-17	TET2, TET2-AS1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90016614	Peyrot WJ	2021	170,756	18,381	Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST007777	Schork AJ	2019	46,008	19,526	A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment.
GCST90016620	Peyrot WJ	2021	40,675	18,381	Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST008417	Demontis D	2019	35,006	16,366	Genome-wide association study implicates CHRNA2 in cannabis use disorder.
GCST90624487	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624492	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624496	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624499	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624501	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624502	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	3
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	36
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	14

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	9
3_prime_UTR_variant	3
non_coding_transcript_exon_variant	2
regulatory_region_variant	2
TF_binding_site_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2352974	3	49853180	C>A,G,T	0.05	intron_variant	TRAIP	7e-35	Tier 4: intronic/intergenic
rs7623659	3	49377358	C>T	0.05	intron_variant	RHOA	2e-31	Tier 4: intronic/intergenic
rs13217619	6	28338894	T>C	0.05	intron_variant	ZSCAN31	1e-27	Tier 4: intronic/intergenic
rs11793831	9	23362313	G>A,T	0.05	intron_variant	LINC03142	1e-27	Tier 4: intronic/intergenic
rs115329265	6	28744470			intron_variant	RPSAP2 - NOP56P1	2e-27	Tier 4: intronic/intergenic
rs55838312	4	105243127	T>A,G	0.05	intron_variant	TET2-AS1, TET2	8e-27	Tier 4: intronic/intergenic
rs116137698	6	28699892			intron_variant	LINC00533	3e-26	Tier 4: intronic/intergenic
rs2008514	16	28814284	G>A,C,T	0.05	non_coding_transcript_exon_variant	PLA2G10KP - ATXN2L	4e-26	Tier 4: intronic/intergenic
rs141342723	6	27654305	T>C	0.05	intergenic_variant	RPL8P1 - LINC01012	4e-24	Tier 4: intronic/intergenic
rs75782365	6	26408323	T>G	0.05	intron_variant	BTN3A1	8e-24	Tier 4: intronic/intergenic
rs9384679	6	108543216	C>A,T	0.05	intron_variant	AFG1L - FOXO3	4e-23	Tier 4: intronic/intergenic
rs151267808	6	29882943			intron_variant	POLR1HASP, POLR1HASP	1e-22	Tier 4: intronic/intergenic
rs3128341	1	72284165	T>A,C	0.05	non_coding_transcript_exon_variant	LINC02796	9e-22	Tier 4: intronic/intergenic
rs7746199	6	27293545	C>A,T	0.05	regulatory_region_variant	POM121L2	1e-20	Tier 3: regulatory
rs56150095	7	72294084	C>A,G,T	0.05	intron_variant	CALN1	3e-20	Tier 4: intronic/intergenic
rs114115252	6	30931418			3_prime_UTR_variant	SFTA2	8e-20	Tier 2: splice/UTR
rs4298967	12	2299028	A>C,G,T	0.05	intron_variant	CACNA1C, CACNA1C-IT3	8e-20	Tier 4: intronic/intergenic
rs1782810	1	98036784	G>A,C,T	0.05	intron_variant	MIR137HG	1e-19	Tier 4: intronic/intergenic
rs6921919	6	28357424	C>G	0.05	intron_variant	ZKSCAN3	1e-19	Tier 4: intronic/intergenic
rs1486091	1	72105681	C>T	0.05	intron_variant	NEGR1	1e-19	Tier 4: intronic/intergenic
rs9467711	6	26332377	A>C	0.05	intron_variant	H3C9P - BTN3A2	3e-19	Tier 4: intronic/intergenic
rs28888764	16	28817907	A>C,G,T	0.05	intergenic_variant	PLA2G10KP - ATXN2L	4e-19	Tier 4: intronic/intergenic
rs67981811	6	28387058	C>G	0.05	3_prime_UTR_variant	ZSCAN12	5e-19	Tier 2: splice/UTR
rs115707823	6	30374976			intergenic_variant	UBQLN1P1 - MICC	6e-18	Tier 4: intronic/intergenic
rs116633139	6	32700133			intergenic_variant	HLA-DQB1 - MTCO3P1	6e-18	Tier 4: intronic/intergenic
rs10733389	9	23378222	A>C,G,T	0.05	intron_variant	LINC03142	6e-18	Tier 4: intronic/intergenic
rs115123779	6	29510044			intron_variant	LINC02829	1e-17	Tier 4: intronic/intergenic
rs7531118	1	72371556	T>C	0.05	intron_variant	LINC02796	1e-17	Tier 4: intronic/intergenic
rs1054442	12	48995537	A>C,G,T	0.05	3_prime_UTR_variant	DDN	1e-17	Tier 2: splice/UTR
rs2454205	4	105263072	C>T	0.05	intron_variant	TET2, TET2-AS1	1e-17	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

179 uncertain significance, 136 likely benign, 110 pathogenic, 63 likely pathogenic, 44 conflicting classifications of pathogenicity, 40 association, 19 pathogenic/likely pathogenic, 5 benign/likely benign, 4 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
236304	Single allele		Pathogenic	criteria provided, single submitter
236305	Single allele		Pathogenic	criteria provided, single submitter
236306	Single allele		Pathogenic	criteria provided, single submitter
236308	Single allele		Pathogenic	criteria provided, single submitter
236309	Single allele		Pathogenic	criteria provided, single submitter
236310	Single allele		Pathogenic	criteria provided, single submitter
236313	Single allele		Pathogenic	criteria provided, single submitter
236314	Single allele		Pathogenic	criteria provided, single submitter
236315	Single allele		Pathogenic	criteria provided, single submitter
236316	Single allele		Pathogenic	criteria provided, single submitter
236317	Single allele		Pathogenic	criteria provided, single submitter
236318	Single allele		Pathogenic	criteria provided, single submitter
236319	Single allele		Pathogenic	criteria provided, single submitter
236321	Single allele		Pathogenic	criteria provided, single submitter
236322	Single allele		Pathogenic	criteria provided, single submitter
236324	Single allele		Pathogenic	criteria provided, single submitter
236325	Single allele		Pathogenic	criteria provided, single submitter
236326	Single allele		Pathogenic	criteria provided, single submitter
236327	Single allele		Pathogenic	criteria provided, single submitter
236328	Single allele		Pathogenic	criteria provided, single submitter
236377	Single allele	AATF	Pathogenic	criteria provided, single submitter
3024382	GRCh38/hg38 17q12(chr17:36466109-37946106)	AATF	Pathogenic	no assertion criteria provided
3024381	GRCh38/hg38 16p13.11(chr16:15399656-16194269)	ABCC1	Pathogenic	no assertion criteria provided
3024387	GRCh38/hg38 16p13.11-12.3(chr16:15184811-18708191)	ABCC1	Pathogenic	no assertion criteria provided
236380	Single allele	ABHD11	Pathogenic	criteria provided, single submitter
236374	Single allele	ACP6	Pathogenic	criteria provided, single submitter
236375	Single allele	ACP6	Pathogenic	criteria provided, single submitter
3024561	GRCh37/hg19 1q21.1-21.2(chr1:145421717-148193211)	ACP6	Pathogenic	no assertion criteria provided
223117	Single allele	ACR	Pathogenic	no assertion criteria provided
1344715	NM_016188.5(ACTL6B):c.1177G>A (p.Gly393Arg)	ACTL6B	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 73 · Orphanet: 57 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 11

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
TCF4	TCF4	GWAS, GenCC, Orphanet
CSMD1	CSMD1	GWAS, GenCC
SMARCA2	SMARCA2	GWAS, Orphanet
CACNA1C	CACNA1C	GWAS, Orphanet
CACNB2	CACNB2	GWAS, Orphanet
ZMIZ1	ZMIZ1	GWAS, Orphanet
CYCSP5	CYCSP5	GWAS
CSNK2B	CSNK2B	GWAS, Orphanet
ATP6V1G2-DDX39B	ATP6V1G2-DDX39B	GWAS
GRIN2A	GRIN2A	GWAS, Orphanet
RERE	RERE	GWAS, Orphanet

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
CAPRIN1	Definitive	Autosomal dominant	neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder	4
GIGYF1	Strong	Autosomal dominant	autism spectrum disorder	3
WDFY3	Moderate	Autosomal dominant	autism spectrum disorder	5
ADGRG4	Limited	Autosomal dominant	autism spectrum disorder
ASTN2	Limited	Autosomal dominant	autism spectrum disorder	3
CORO1A	Limited	Autosomal dominant	autism spectrum disorder	6
CSMD1	Limited	Autosomal dominant	autism spectrum disorder	2
CTTNBP2	Limited	Autosomal dominant	autism spectrum disorder
DIP2A	Limited	Autosomal dominant	autism spectrum disorder
RFX3	Limited	Autosomal dominant	autism spectrum disorder	3
SLC7A3	Limited	Autosomal dominant	autism spectrum disorder
STXBP1	Limited	Autosomal dominant	autism spectrum disorder	12
TAOK2	Limited	Autosomal dominant	autism spectrum disorder	4
TCF4	Limited	Autosomal dominant	autism spectrum disorder	11
TM9SF4	Limited	Autosomal dominant	autism spectrum disorder
VEZF1	Limited	Autosomal dominant	autism spectrum disorder	4
ZC3H12B	Limited	Autosomal dominant	autism spectrum disorder
CNTN4	Disputed Evidence	Autosomal dominant	autism spectrum disorder
SLC6A4	Disputed Evidence	Autosomal dominant	autism spectrum disorder	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCF4	Orphanet:171	Primary sclerosing cholangitis
TCF4	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
TCF4	Orphanet:2896	Pitt-Hopkins syndrome
TCF4	Orphanet:98974	Fuchs endothelial corneal dystrophy
SMARCA2	Orphanet:3051	Nicolaides-Baraitser syndrome
SMARCA2	Orphanet:637013	SMARCA2-related blepharophimosis-intellectual disability syndrome
STXBP1	Orphanet:495818	9q33.3q34.11 microdeletion syndrome
STXBP1	Orphanet:599373	STXBP1-related encephalopathy
CACNA1C	Orphanet:101016	Romano-Ward syndrome
CACNA1C	Orphanet:130	Brugada syndrome
CACNA1C	Orphanet:528084	Non-specific syndromic intellectual disability
CACNA1C	Orphanet:595098	Timothy syndrome type 1
CACNA1C	Orphanet:595105	Timothy syndrome type 2
CACNA1C	Orphanet:595109	Atypical Timothy syndrome
CACNB2	Orphanet:130	Brugada syndrome
ZMIZ1	Orphanet:528084	Non-specific syndromic intellectual disability
WDFY3	Orphanet:528084	Non-specific syndromic intellectual disability
CORO1A	Orphanet:228003	Severe combined immunodeficiency due to CORO1A deficiency
CSNK2B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
CSNK2B	Orphanet:689397	Poirier-Bienvenu neurodevelopmental syndrome
GRIN2A	Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome
GRIN2A	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
GRIN2A	Orphanet:289266	Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation
GRIN2A	Orphanet:725	Developmental and epileptic encephalopathy with spike-wave activation in sleep
GRIN2A	Orphanet:98818	Landau-Kleffner syndrome
CAPRIN1	Orphanet:528084	Non-specific syndromic intellectual disability
RERE	Orphanet:1606	1p36 deletion syndrome
RERE	Orphanet:494344	RERE-related neurodevelopmental syndrome
VEZF1	Orphanet:154	Familial isolated dilated cardiomyopathy
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
SATB1	Orphanet:684232	Intellectual disability-epilepsy-dental anomalies-facial dysmorphism syndrome
SBF1	Orphanet:363981	Charcot-Marie-Tooth disease type 4B3
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
SCN9A	Orphanet:306577	Hereditary sodium channelopathy-related small fibers neuropathy
SCN9A	Orphanet:33069	Dravet syndrome
SCN9A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN9A	Orphanet:46348	Paroxysmal extreme pain disorder
SCN9A	Orphanet:88642	Congenital insensitivity to pain-anosmia-neuropathic arthropathy
SCN9A	Orphanet:90026	Primary erythromelalgia
SCN9A	Orphanet:970	Hereditary sensory and autonomic neuropathy type 2
SEMA3A	Orphanet:130	Brugada syndrome
SEMA3A	Orphanet:478	Kallmann syndrome

Cohort genes → proteins

52 cohort genes, 48 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	14
gwas_and_clinvar	9
multi_evidence	29

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCF4	HGNC:11634	ENSG00000196628	P15884	Transcription factor 4	gwas,gencc,clinvar
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas,gencc,clinvar
SMARCA2	HGNC:11098	ENSG00000080503	P51531	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	gwas,clinvar
STXBP1	HGNC:11444	ENSG00000136854	P61764	Syntaxin-binding protein 1	gencc,clinvar
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	gwas,clinvar
CACNB2	HGNC:1402	ENSG00000165995	Q08289	Voltage-dependent L-type calcium channel subunit beta-2	gwas,clinvar
ZMIZ1	HGNC:16493	ENSG00000108175	Q9ULJ6	Zinc finger MIZ domain-containing protein 1	gwas,clinvar
DIP2A	HGNC:17217	ENSG00000160305	Q14689	Disco-interacting protein 2 homolog A	gencc,clinvar
WDFY3	HGNC:20751	ENSG00000163625	Q8IZQ1	WD repeat and FYVE domain-containing protein 3	gencc,clinvar
CNTN4	HGNC:2174	ENSG00000144619	Q8IWV2	Contactin-4	gencc,clinvar
CORO1A	HGNC:2252	ENSG00000102879	P31146	Coronin-1A	gencc,clinvar
CYCSP5	HGNC:24416	ENSG00000227735		CYCS pseudogene 5	gwas,clinvar
CSNK2B	HGNC:2460	ENSG00000204435	P67870	Casein kinase II subunit beta	gwas,clinvar
TM9SF4	HGNC:30797	ENSG00000101337	Q92544	Transmembrane 9 superfamily member 4	gencc,clinvar
ATP6V1G2-DDX39B	HGNC:41999	ENSG00000254870		ATP6V1G2-DDX39B readthrough (NMD candidate)	gwas,clinvar
GRIN2A	HGNC:4585	ENSG00000183454	Q12879	Glutamate receptor ionotropic, NMDA 2A	gwas,clinvar
CAPRIN1	HGNC:6743	ENSG00000135387	Q14444	Caprin-1	gencc,clinvar
GIGYF1	HGNC:9126	ENSG00000146830	O75420	GRB10-interacting GYF protein 1	gencc,clinvar
RERE	HGNC:9965	ENSG00000142599	Q9P2R6	Arginine-glutamic acid dipeptide repeats protein	gwas,clinvar
RFX3	HGNC:9984	ENSG00000080298	P48380	Transcription factor RFX3	gencc,clinvar
SLC6A4	HGNC:11050	ENSG00000108576	P31645	Sodium-dependent serotonin transporter	gencc
SLC7A3	HGNC:11061	ENSG00000165349	Q8WY07	Cationic amino acid transporter 3	gencc
VEZF1	HGNC:12949	ENSG00000136451	Q14119	Vascular endothelial zinc finger 1	gencc
CTTNBP2	HGNC:15679	ENSG00000077063	Q8WZ74	Cortactin-binding protein 2	gencc
TAOK2	HGNC:16835	ENSG00000149930	Q9UL54	Serine/threonine-protein kinase TAO2	gencc
ASTN2	HGNC:17021	ENSG00000148219	O75129	Astrotactin-2	gencc
ZC3H12B	HGNC:17407	ENSG00000102053	Q5HYM0	Probable ribonuclease ZC3H12B	gencc
ADGRG4	HGNC:18992	ENSG00000156920	Q8IZF6	Adhesion G-protein coupled receptor G4	gencc
RIT2	HGNC:10017	ENSG00000152214	Q99578	GTP-binding protein Rit2	gwas
TRIM38	HGNC:10059	ENSG00000112343	O00635	E3 ubiquitin-protein ligase TRIM38	gwas
TRIM39	HGNC:10065	ENSG00000204599	Q9HCM9	E3 ubiquitin-protein ligase TRIM39	gwas
RNF5	HGNC:10068	ENSG00000204308	Q99942	E3 ubiquitin-protein ligase RNF5	gwas
SNORD48	HGNC:10188	ENSG00000201823		small nucleolar RNA, C/D box 48	gwas
SNORD52	HGNC:10202	ENSG00000201754		small nucleolar RNA, C/D box 52	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	gwas
RPS6KA2	HGNC:10431	ENSG00000071242	Q15349	Ribosomal protein S6 kinase alpha-2	clinvar
SATB1	HGNC:10541	ENSG00000182568	Q01826	DNA-binding protein SATB1	clinvar
SBF1	HGNC:10542	ENSG00000100241	O95248	Myotubularin-related protein 5	clinvar
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	clinvar
SCN9A	HGNC:10597	ENSG00000169432	Q15858	Sodium channel protein type 9 subunit alpha	clinvar
SEC13	HGNC:10697	ENSG00000157020	P55735	Protein SEC13 homolog	gwas
SEMA3A	HGNC:10723	ENSG00000075213	Q14563	Semaphorin-3A	gwas
SRSF1	HGNC:10780	ENSG00000136450	Q07955	Serine/arginine-rich splicing factor 1	clinvar
SRSF11	HGNC:10782	ENSG00000116754	Q05519	Serine/arginine-rich splicing factor 11	clinvar
SKI	HGNC:10896	ENSG00000157933	P12755	Ski oncogene	clinvar
SKIC2	HGNC:10898	ENSG00000204351	Q15477	Superkiller complex protein 2	gwas
DST	HGNC:1090	ENSG00000151914	Q03001	Dystonin	clinvar
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	clinvar
SLC17A1	HGNC:10929	ENSG00000124568	Q14916	Sodium-dependent phosphate transport protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCF4	Transcription factor 4	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
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).
STXBP1	Syntaxin-binding protein 1	Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins.
CACNA1C	Voltage-dependent L-type calcium channel subunit alpha-1C	Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
CACNB2	Voltage-dependent L-type calcium channel subunit beta-2	Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current.
ZMIZ1	Zinc finger MIZ domain-containing protein 1	Acts as a transcriptional coactivator.
DIP2A	Disco-interacting protein 2 homolog A	Catalyzes the de novo synthesis of acetyl-CoA in vitro.
WDFY3	WD repeat and FYVE domain-containing protein 3	Required for selective macroautophagy (aggrephagy).
CNTN4	Contactin-4	Contactins mediate cell surface interactions during nervous system development.
CORO1A	Coronin-1A	May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion.
CSNK2B	Casein kinase II subunit beta	Regulatory subunit of casein kinase II/CK2.
TM9SF4	Transmembrane 9 superfamily member 4	Associates with proteins harboring glycine-rich transmembrane domains and ensures their efficient localization to the cell surface.
GRIN2A	Glutamate receptor ionotropic, NMDA 2A	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
CAPRIN1	Caprin-1	mRNA-binding protein that acts as a regulator of mRNAs transport, translation and/or stability, and which is involved in neurogenesis, synaptic plasticity in neurons and cell proliferation and migration in multiple cell types.
GIGYF1	GRB10-interacting GYF protein 1	May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling.
RERE	Arginine-glutamic acid dipeptide repeats protein	Plays a role as a transcriptional repressor during development.
RFX3	Transcription factor RFX3	Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development.
SLC6A4	Sodium-dependent serotonin transporter	Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle.
SLC7A3	Cationic amino acid transporter 3	Uniporter that mediates the uptake of cationic L-amino acids such as L-arginine, L-lysine and L-ornithine.
VEZF1	Vascular endothelial zinc finger 1	Possible transcription factor.
CTTNBP2	Cortactin-binding protein 2	Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance.
TAOK2	Serine/threonine-protein kinase TAO2	Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade.
ASTN2	Astrotactin-2	Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons.
ZC3H12B	Probable ribonuclease ZC3H12B	May function as RNase and regulate the levels of target RNA species.
ADGRG4	Adhesion G-protein coupled receptor G4	Orphan adhesion G-protein coupled receptor (aGPCR).
RIT2	GTP-binding protein Rit2	Binds and exchanges GTP and GDP.
TRIM38	E3 ubiquitin-protein ligase TRIM38	E3 ubiquitin-protein and E3 SUMO-protein ligase that acts as a regulator of innate immunity.
TRIM39	E3 ubiquitin-protein ligase TRIM39	E3 ubiquitin-protein ligase.
RNF5	E3 ubiquitin-protein ligase RNF5	Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
CFB	Complement factor B	Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
RPS6KA2	Ribosomal protein S6 kinase alpha-2	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, su…
SATB1	DNA-binding protein SATB1	Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma.
SBF1	Myotubularin-related protein 5	Acts as an adapter for the phosphatase MTMR2 to regulate MTMR2 catalytic activity and subcellular location.
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of excitable membranes.
SCN9A	Sodium channel protein type 9 subunit alpha	Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SEC13	Protein SEC13 homolog	Functions as a component of the nuclear pore complex (NPC) and the COPII coat.
SEMA3A	Semaphorin-3A	Involved in the development of the olfactory system and in neuronal control of puberty.
SRSF1	Serine/arginine-rich splicing factor 1	Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing.
SRSF11	Serine/arginine-rich splicing factor 11	May function in pre-mRNA splicing.
SKI	Ski oncogene	May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage.
SKIC2	Superkiller complex protein 2	Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways.
DST	Dystonin	Cytoskeletal linker protein.
SLC12A2	Solute carrier family 12 member 2	Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.
SLC17A1	Sodium-dependent phosphate transport protein 1	Important for the resorption of phosphate by the kidney.
SLC17A3	Sodium-dependent phosphate transport protein 4	Mediates the renal excretion of uremic toxin 3-indoxyl sulfate.
SLC17A4	Probable small intestine urate exporter	Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions.

Protein-family classification

Druggable: 16 · Difficult: 15 · Unknown: 21 · Druggable fraction: 0.31

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
Complement	2	10.3×	0.089
Ion channel	3	6.4×	0.089
Transporter	3	4.5×	0.107
Transcription factor	10	1.6×	0.252
Scaffold/PPI	5	1.7×	0.397
Kinase	3	1.6×	0.530
Phosphatase	1	1.6×	0.730
Antibody/Immunoglobulin	2	1.1×	0.737
Protease	1	0.7×	0.933
GPCR	1	0.5×	0.981
Other/Unknown	21	0.7×	0.991

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCF4	Transcription factor	no	7.6.2.3	bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
SMARCA2	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
STXBP1	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CACNB2	Scaffold/PPI	no		VDCC_L_bsu, SH3_domain, VDCC_L_b2su
ZMIZ1	Transcription factor	no		Znf_MIZ, Znf_RING/FYVE/PHD, ZMIZ1_N
DIP2A	Other/Unknown	no		AMP-dep_synth/lig_dom, DMAP1-bd, AMP-bd_C
WDFY3	Transcription factor	no		Znf_FYVE, BEACH_dom, WD40_rpt
CNTN4	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
CORO1A	Scaffold/PPI	no		WD40_rpt, DUF1899, Trimer_CC
CYCSP5	Other/Unknown	no
CSNK2B	Kinase	yes		Casein_kinase_II_reg-sub, Casein_kin_II_reg-sub_N, Casein_kinase_II_beta-like
TM9SF4	Other/Unknown	no		EMP70
ATP6V1G2-DDX39B	Other/Unknown	no
GRIN2A	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
CAPRIN1	Other/Unknown	no		Caprin-1_C, Caprin, Caprin-1_dimer
GIGYF1	Other/Unknown	no		GYF, GYF-like_dom_sf, GRB10-interact_GYF
RERE	Transcription factor	no		Znf_GATA, ELM2_dom, SANT/Myb
RFX3	Other/Unknown	no		DNA-bd_RFX, RFX1_trans_act, WH-like_DNA-bd_sf
SLC6A4	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_serotonin_N, SNS_sf
SLC7A3	Other/Unknown	no		AA/rel_permease1, Cat_AA_permease, CAT_C
VEZF1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
CTTNBP2	Scaffold/PPI	no		Ankyrin_rpt, Cortactin-binding_p2_N, Ankyrin_rpt-contain_sf
TAOK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ASTN2	Complement	yes		MACPF, Astrotactin, FN3_sf
ZC3H12B	Transcription factor	no		Znf_CCCH, RNase_Zc3h12_NYN, Rege-1_UBA-like
ADGRG4	GPCR	yes		GPS, GPCR_2_secretin-like, PTX_dom
RIT2	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
TRIM38	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
TRIM39	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
RNF5	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
SNORD48	Other/Unknown	no
SNORD52	Other/Unknown	no
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
RPS6KA2	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
SATB1	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
SBF1	Phosphatase	yes	3.1.3.16	cDENN_dom, PH_domain, GRAM
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SCN9A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SEC13	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
SEMA3A	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
SRSF1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, SRSF1_RRM2
SRSF11	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RRM_SRSF11
SKI	Other/Unknown	no		SKI/SNO/DAC, DNA-bd_dom_put_sf, SAND-like_dom_sf
SKIC2	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Ski2/MTR4_C
DST	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom
SLC17A1	Transporter	yes		Pi_cotranspt, MFS, MFS_dom

Expression context

Cohort genes with no expression data: 0.

45 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)	51
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	7
Brodmann (1909) area 23	5
cortical plate	5
buccal mucosa cell	5
primordial germ cell in gonad	5
middle temporal gyrus	4
colonic epithelium	4
corpus callosum	4
stromal cell of endometrium	4
cerebellar hemisphere	4
calcaneal tendon	3
left testis	3
ganglionic eminence	3
ventricular zone	3
right hemisphere of cerebellum	3
jejunal mucosa	3
medial globus pallidus	3
adult mammalian kidney	3
liver	3
right lobe of liver	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCF4	292	ubiquitous	marker	endothelial cell, skin of hip, pericardium
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
SMARCA2	301	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate
STXBP1	287	ubiquitous	marker	middle temporal gyrus, lateral nuclear group of thalamus, Brodmann (1909) area 23
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
CACNB2	237	broad	marker	adrenal tissue, mucosa of stomach, buccal mucosa cell
ZMIZ1	295	ubiquitous	marker	dorsal motor nucleus of vagus nerve, tibia, seminal vesicle
DIP2A	273	ubiquitous	marker	visceral pleura, blood vessel layer, parietal pleura
WDFY3	293	ubiquitous	marker	sural nerve, calcaneal tendon, corpus callosum
CNTN4	214	broad	marker	sperm, buccal mucosa cell, lateral nuclear group of thalamus
CORO1A	252	ubiquitous	marker	granulocyte, monocyte, leukocyte
CYCSP5	97		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, corpus callosum
CSNK2B	134	ubiquitous	marker	left testis, right testis, skin of leg
TM9SF4	296	ubiquitous	marker	stromal cell of endometrium, monocyte, mononuclear cell
ATP6V1G2-DDX39B	130	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, sural nerve
GRIN2A	199	broad	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus
CAPRIN1	294	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
GIGYF1	242	ubiquitous	marker	sural nerve, right hemisphere of cerebellum, cerebellar hemisphere
RERE	293	ubiquitous	marker	sural nerve, colonic epithelium, gastrocnemius
RFX3	253	ubiquitous	marker	bronchial epithelial cell, mucosa of paranasal sinus, Brodmann (1909) area 23
SLC6A4	162	tissue_specific	marker	right lung, jejunal mucosa, ileal mucosa
SLC7A3	111	broad	marker	cauda epididymis, primordial germ cell in gonad, tibialis anterior
VEZF1	292	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, ventricular zone
CTTNBP2	230	broad	marker	cortical plate, corpus callosum, embryo
TAOK2	211	ubiquitous	marker	right hemisphere of cerebellum, apex of heart, cerebellar hemisphere
ASTN2	236	ubiquitous	marker	buccal mucosa cell, trigeminal ganglion, dorsal root ganglion
ZC3H12B	177		marker	tibialis anterior, prefrontal cortex, primordial germ cell in gonad
ADGRG4	55	tissue_specific	marker	buccal mucosa cell, duodenum, jejunal mucosa
RIT2	128	tissue_specific	marker	cerebellar cortex, cerebellar hemisphere, cerebellum
TRIM38	285	ubiquitous	marker	cardia of stomach, renal medulla, pylorus

Protein interactions among cohort

Intra-cohort edges: 12.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRSF1	5,828
SMARCA2	4,237
SEC13	4,071
CORO1A	3,620
TCF4	3,342
DIP2A	3,262
RIT2	3,234
GRIN2A	3,146
CACNA1C	3,145
STXBP1	3,003

Intra-cohort edges

A	B	Sources
ASTN2	CNTN4	string_interaction
CACNA1C	CACNB2	intact, string_interaction
CACNA1C	CSMD1	string_interaction
CACNA1C	SCN2A	intact
CACNA1C	SCN9A	intact
CSNK2B	RPS6KA2	intact
DIP2A	TRIM39	biogrid_interaction
SATB1	ZMIZ1	biogrid_interaction
SCN2A	SCN9A	intact
SCN2A	STXBP1	string_interaction
STXBP1	TRIM38	biogrid_interaction, intact
TRIM39	WDFY3	biogrid_interaction

Structural data

PDB: 29 · AlphaFold-only: 19 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN9A	Q15858	43
GRIN2A	Q12879	37
CACNA1C	Q13936	33
SMARCA2	P51531	32
SLC6A4	P31645	30
CFB	P00751	26
SLC12A2	P55011	14
SEC13	P55735	11
SKIC2	Q15477	11
CSNK2B	P67870	10
SRSF1	Q07955	10
SATB1	Q01826	8
CNNM2	Q9H8M5	7
CAPRIN1	Q14444	6
TCF4	P15884	5
SCN2A	Q99250	5
SKI	P12755	4
CACNB2	Q08289	3
ASTN2	O75129	3
TRIM39	Q9HCM9	3
WDFY3	Q8IZQ1	2
GIGYF1	O75420	2
ADGRG4	Q8IZF6	2
DST	Q03001	2
CSMD1	Q96PZ7	1
STXBP1	P61764	1
ZMIZ1	Q9ULJ6	1
RERE	Q9P2R6	1
ZC3H12B	Q5HYM0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CORO1A	P31146	93.25
RIT2	Q99578	88.46
TRIM38	O00635	87.31
CNTN4	Q8IWV2	86.72
SLC17A1	Q14916	86.54
TM9SF4	Q92544	85.71
SEMA3A	Q14563	84.50
SLC17A4	Q9Y2C5	83.87
SLC7A3	Q8WY07	83.55
SLC17A3	O00476	79.15
DIP2A	Q14689	78.93
RPS6KA2	Q15349	77.37
SBF1	O95248	74.72
RNF5	Q99942	68.71
RFX3	P48380	67.90
TAOK2	Q9UL54	67.17
VEZF1	Q14119	60.93
CTTNBP2	Q8WZ74	58.83
SRSF11	Q05519	55.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 585. Enrichment computed across 250 evidence-associated genes (156 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 156 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Butyrophilin (BTN) family interactions	7	39.4×	7e-08	BTN1A1, BTN2A1, BTN2A2, BTN3A1, BTN3A2, BTN3A3, BTNL2
Chromatin organization	15	7.8×	2e-07	SMARCA2, SMARCB1, SMARCC1, ARID1A, KDM6A, KAT6A, KDM3B, KMT2C (+7 more)
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	9	17.3×	3e-07	SMARCA2, CSNK2B, SMARCB1, SMARCC1, ARID1A, AUTS2, ACTL6B, ARID2 (+1 more)
Chromatin modifying enzymes	15	7.0×	5e-07	SMARCA2, SMARCB1, SMARCC1, ARID1A, KDM6A, KAT6A, KDM3B, KMT2C (+7 more)
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	7	20.5×	4e-06	SMARCA2, SMARCB1, SMARCC1, ARID1A, BCL11B, ACTL6B, ARID1B
Transcriptional regulation by RUNX1	10	9.4×	9e-06	SMARCA2, SMARCB1, SMARCC1, ARID1A, KMT2C, AUTS2, KMT2B, ACTL6B (+2 more)
RNA Polymerase II Transcription	22	3.2×	1e-04	SMARCA2, SRSF1, SRSF11, SKI, SMARCB1, SMARCC1, ARID1A, TAF1 (+14 more)
Formation of the canonical BAF (cBAF) complex	5	20.3×	2e-04	SMARCA2, SMARCB1, SMARCC1, ARID1A, ARID1B
Phase 0 - rapid depolarisation	6	13.3×	3e-04	CACNA1C, CACNB2, SCN2A, SCN9A, CAMK2A, CAMK2B
Gene expression (Transcription)	24	2.8×	3e-04	SMARCA2, SEC13, SRSF1, SRSF11, SKI, SMARCB1, SMARCC1, ARID1A (+16 more)
RMTs methylate histone arginines	8	7.5×	6e-04	SMARCA2, SMARCB1, SMARCC1, ARID1A, H2AC12, ACTL6B, ARID2, ARID1B
Regulation of endogenous retroelements	5	11.8×	0.003	SMARCA2, SMARCB1, SMARCC1, ARID1A, ARID1B
Formation of the polybromo-BAF (pBAF) complex	4	16.3×	0.004	SMARCA2, SMARCB1, SMARCC1, ARID2
Formation of the embryonic stem cell BAF (esBAF) complex	4	15.4×	0.005	SMARCB1, SMARCC1, ARID1A, BCL11B
Activation of C3 and C5	3	24.4×	0.008	CFB, C2, C4A
Generic Transcription Pathway	23	2.2×	0.009	SMARCA2, SKI, SMARCB1, SMARCC1, ARID1A, TAF1, ZNF184, ZKSCAN8 (+15 more)
Regulation of MITF-M-dependent genes involved in pigmentation	5	8.5×	0.010	SMARCA2, SMARCB1, SMARCC1, ARID1A, ARID1B
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	3	16.9×	0.021	RPS6KA2, CAMK2A, CAMK2B
Regulation of insulin secretion	5	7.0×	0.021	STXBP1, CACNA1C, CACNB2, CACNA1A, CACNA1D
Transmission across Chemical Synapses	8	3.9×	0.030	CACNB2, RPS6KA2, SLC6A1, SLC6A4, CACNA1A, ARHGEF9, CAMK2A, CAMK2B
Neurexins and neuroligins	5	6.3×	0.032	STXBP1, GRIN2A, NLGN4X, NLGN3, SHANK2
Epigenetic regulation of gene expression	8	3.7×	0.042	SMARCA2, SMARCB1, SMARCC1, ARID1A, KDM6A, KMT2C, KMT2B, ARID1B
MITF-M-dependent gene expression	5	5.8×	0.042	SMARCA2, SMARCB1, SMARCC1, ARID1A, ARID1B
Inhibition of TSC complex formation by AKT (PKB)	2	29.3×	0.042	TSC1, TSC2
GABA synthesis, release, reuptake and degradation	3	12.2×	0.042	STXBP1, SLC6A1, RIMS1
Integration of energy metabolism	5	5.6×	0.043	STXBP1, CACNA1C, CACNB2, CACNA1A, CACNA1D
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	6	4.5×	0.045	SMARCA2, SMARCB1, SMARCC1, ARID1A, H2BC12, ARID1B
Unblocking of NMDA receptors, glutamate binding and activation	3	10.5×	0.052	GRIN2A, CAMK2A, CAMK2B
Negative regulation of NMDA receptor-mediated neuronal transmission	3	10.5×	0.052	GRIN2A, CAMK2A, CAMK2B
NCAM signaling for neurite out-growth	4	7.0×	0.052	CACNA1C, CACNB2, SPTAN1, CACNA1D

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 216 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 G0 to G1 transition	7	21.9×	1e-05	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
positive regulation of T cell differentiation	8	16.9×	1e-05	SMARCA2, ZMIZ1, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
regulation of cytokine production	10	11.5×	1e-05	BTN1A1, BTN2A1, BTN2A2, BTN3A1, BTN3A2, BTN3A3, BTNL2, BTN2A3P (+2 more)
regulation of nucleotide-excision repair	7	19.5×	2e-05	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
regulation of mitotic metaphase/anaphase transition	7	16.1×	6e-05	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
synapse organization	8	10.4×	2e-04	CNTN4, SLC6A1, TSC1, PRRT1, NLGN4X, NLGN3, SHANK3, SHANK2
positive regulation of myoblast differentiation	7	11.9×	4e-04	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
phosphate ion transport	4	34.7×	4e-04	SLC17A1, SLC17A3, SLC34A1, SLC17A6
sodium-dependent phosphate transport	4	34.7×	4e-04	SLC17A1, SLC17A4, SLC34A1, SLC17A6
vocalization behavior	5	20.5×	4e-04	CNTNAP2, NLGN4X, NLGN3, SHANK3, SHANK2
positive regulation of double-strand break repair	7	11.2×	4e-04	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
regulation of G1/S transition of mitotic cell cycle	7	9.9×	7e-04	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
regulation of transcription by RNA polymerase II	39	2.1×	7e-04	TCF4, SMARCA2, ZMIZ1, RFX3, SATB1, SMARCB1, SMARCC1, ARID1A (+31 more)
chromatin remodeling	13	4.4×	9e-04	SMARCA2, RERE, SATB1, SMARCB1, SMARCC1, ARID1A, KDM6A, HDAC4 (+5 more)
learning	7	9.1×	0.001	ATP8A1, CNTNAP2, CIC, NLGN4X, NLGN3, SHANK3, SHANK2
positive regulation of cell differentiation	7	8.7×	0.001	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B, ARID2, ARID1B
memory	8	6.8×	0.002	CSMD1, GRIN2A, SCN2A, SLC6A1, SLC6A4, SPG11, CIC, SHANK3
synapse assembly	7	7.5×	0.003	CAPRIN1, NLGN4X, NLGN3, SHANK3, SHANK2, GHRL, CLSTN3
neuron cell-cell adhesion	4	18.4×	0.004	CNTN4, NLGN4X, NLGN3, ASTN2
nervous system development	15	3.2×	0.006	TCF4, SMARCA2, CNTN4, SCN2A, SMARCB1, SMARCC1, ARID1A, TCF12 (+7 more)
adult behavior	5	10.8×	0.006	CNTNAP2, NLGN4X, NLGN3, SHANK3, SHANK2
sodium ion transmembrane transport	7	6.6×	0.006	GRIN2A, SCN2A, SCN9A, SLC12A2, SLC6A1, SLC6A4, NALCN
T cell receptor signaling pathway	8	5.6×	0.006	BTN1A1, BTN2A1, BTN2A2, BTN3A1, BTN3A2, BTN3A3, BTNL2, BTN2A3P
nucleosome disassembly	4	14.9×	0.008	SMARCB1, SMARCC1, ARID1A, ARID2
social behavior	6	7.5×	0.008	CNTNAP2, CIC, NLGN4X, NLGN3, SHANK3, SHANK2
inorganic anion import across plasma membrane	2	78.0×	0.009	SLC12A2, SLC6A1
conditioned place preference	3	23.4×	0.012	CSMD1, SLC6A4, TACR3
cardiac muscle cell action potential involved in contraction	4	13.0×	0.012	CACNA1C, SCN2A, SCN9A, CACNA1D
sodium ion import across plasma membrane	4	11.6×	0.018	SLC12A2, SLC34A1, SLC6A1, SLC9A3
positive regulation of stem cell population maintenance	5	8.0×	0.019	SMARCA2, SMARCB1, SMARCC1, ARID1A, ACTL6B

Therapeutics

Drugs indicated for this disease

0 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Arbaclofen	Phase 3 (in late-stage trials)
Aripiprazole	Phase 3 (in late-stage trials)
Balovaptan	Phase 3 (in late-stage trials)
Bumetanide	Phase 3 (in late-stage trials)
Cannabinol	Phase 3 (in late-stage trials)
Cariprazine	Phase 3 (in late-stage trials)
Lithium Carbonate	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Memantine	Phase 3 (in late-stage trials)
Mirtazapine	Phase 3 (in late-stage trials)
Oxytocin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acamprosate, Acetylcysteine, Buspirone, Cannabidiol, Clonidine, Dexmedetomidine, Doconexent, Donepezil, Dronabinol, Esomeprazole, Icosapent, Ketamine, Levodopa, OMEGA-3 FATTY ACIDS, OMEGA-3-ACID ETHYL ESTERS, Oxygen, Pioglitazone, Pitolisant, Pregnenolone Succinate, Racemetyrosine, Riluzole, Risperidone, Sertraline, Sodium Chloride, Sulforaphane, Vasopressin, Vatiquinone, Wax, Emulsifying.

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 11 · Phased (≥1): 14 · Undrugged: 38

Druggability breadth: 89 of 250 evidence-associated genes (36%) 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
CACNA1C	REMIFENTANIL
CACNB2	NIMODIPINE
CSNK2B	PALBOCICLIB
GRIN2A	MEMANTINE HYDROCHLORIDE
SLC6A4	CETIRIZINE
TAOK2	FEDRATINIB
CFB	IPTACOPAN
RPS6KA2	FEDRATINIB
SCN2A	BEPRIDIL
SCN9A	IMIPRAMINE
SLC12A2	BUMETANIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A4	422	4
SCN2A	99	4
CACNA1C	85	4
GRIN2A	37	4
SCN9A	36	4
TAOK2	29	4
RPS6KA2	29	4
CSNK2B	14	4
SMARCA2	2	2
CACNB2	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C, SCN2A, SLC6A4
CLOTRIMAZOLE	4	CACNA1C, SLC6A4
PROPIVERINE	4	CACNA1C
DIBUCAINE	4	CACNA1C, SCN2A
IMIPRAMINE	4	CACNA1C, SCN2A, SCN9A, SLC6A4
DULOXETINE	4	CACNA1C, SLC6A4
QUINIDINE	4	CACNA1C, SCN2A, SLC6A4
ESTRADIOL	4	CACNA1C, SLC6A4
TOLTERODINE	4	CACNA1C, SLC6A4
PIMOZIDE	4	CACNA1C, SCN2A, SCN9A, SLC6A4
NIMODIPINE	4	CACNA1C, CACNB2
NICARDIPINE	4	CACNA1C, SLC6A4
AMLODIPINE	4	CACNA1C
VARDENAFIL	4	CACNA1C
CLEMASTINE	4	CACNA1C, SLC6A4
ISRADIPINE	4	CACNA1C
TERFENADINE	4	CACNA1C, SLC6A4
NISOLDIPINE	4	CACNA1C, SCN2A
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C
NIFEDIPINE	4	CACNA1C, SCN2A, SCN9A
XANOMELINE	4	CACNA1C, SLC6A4
DILTIAZEM	4	CACNA1C, SCN2A, SCN9A
PRENYLAMINE	4	CACNA1C, SCN2A, SLC6A4
OLICERIDINE	4	CACNA1C
PROPRANOLOL	4	CACNA1C, SLC6A4
ALVIMOPAN	4	CACNA1C
ASTEMIZOLE	4	CACNA1C, SLC6A4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
SLC6A4	1,055	Binding:1021, Functional:18, ADMET:9, Toxicity:6, Unclassified:1
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
RPS6KA2	448	Binding:446, ADMET:1, Functional:1
SCN9A	428	Binding:395, Functional:29, ADMET:3, Toxicity:1
CSNK2B	421	Binding:419, Functional:2
GRIN2A	324	Binding:296, Functional:23, ADMET:4, Toxicity:1
SMARCA2	311	Binding:274, Functional:25, ADMET:12
TAOK2	232	Binding:232
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
CFB	33	Binding:33
TCF4	31	Binding:31
CACNB2	22	Binding:20, ADMET:1, Toxicity:1
SLC12A2	13	Binding:9, Functional:4
CORO1A	12	Binding:12
SRSF1	9	Binding:9
CAPRIN1	2	Binding:2
RNF5	2	Binding:2
STXBP1	1	Binding:1
TM9SF4	1	Binding:1
SLC7A3	1	Functional:1
SEC13	1	Binding:1
SLC17A1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TCF4	7.6.2.3	ABC-type glutathione-S-conjugate transporter
CFB	3.4.21.47	alternative-complement-pathway C3/C5 convertase
RPS6KA2	2.7.11.1	non-specific serine/threonine protein kinase
SBF1	3.1.3.16	protein-serine/threonine phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMARCA2	311
CACNA1C	575
CSNK2B	421
GRIN2A	324
SLC6A4	1,055
TAOK2	232
RPS6KA2	448
SCN2A	203
SCN9A	428

Pharmacogenomics

Cohort genes with a PharmGKB record: 51; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
SLC6A4	1

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)
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C, SCN2A, SLC6A4
CLOTRIMAZOLE	4	CACNA1C, SLC6A4
PROPIVERINE	4	CACNA1C
DIBUCAINE	4	CACNA1C, SCN2A
IMIPRAMINE	4	CACNA1C, SCN2A, SCN9A, SLC6A4
DULOXETINE	4	CACNA1C, SLC6A4
QUINIDINE	4	CACNA1C, SCN2A, SLC6A4
ESTRADIOL	4	CACNA1C, SLC6A4
TOLTERODINE	4	CACNA1C, SLC6A4
PIMOZIDE	4	CACNA1C, SCN2A, SCN9A, SLC6A4
NIMODIPINE	4	CACNA1C, CACNB2
NICARDIPINE	4	CACNA1C, SLC6A4
AMLODIPINE	4	CACNA1C
VARDENAFIL	4	CACNA1C
CLEMASTINE	4	CACNA1C, SLC6A4
ISRADIPINE	4	CACNA1C
TERFENADINE	4	CACNA1C, SLC6A4
NISOLDIPINE	4	CACNA1C, SCN2A
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C
NIFEDIPINE	4	CACNA1C, SCN2A, SCN9A
XANOMELINE	4	CACNA1C, SLC6A4
DILTIAZEM	4	CACNA1C, SCN2A, SCN9A
PRENYLAMINE	4	CACNA1C, SCN2A, SLC6A4
OLICERIDINE	4	CACNA1C
PROPRANOLOL	4	CACNA1C, SLC6A4
ALVIMOPAN	4	CACNA1C
ASTEMIZOLE	4	CACNA1C, SLC6A4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	CACNA1C, CACNB2, CSNK2B, GRIN2A, SLC6A4, TAOK2, CFB, RPS6KA2, SCN2A, SCN9A (+1 more)
B	Phased (≥1) drug, not yet approved	3	TCF4, SMARCA2, SRSF1
C	Druggable family + PDB, no drug	3	CSMD1, ASTN2, ADGRG4
D	Druggable family + AlphaFold only, no drug	6	CNTN4, SBF1, SEMA3A, SLC17A1, SLC17A3, SLC17A4
E	Difficult family or no structure, no drug	29	STXBP1, ZMIZ1, DIP2A, WDFY3, CORO1A, CYCSP5, TM9SF4, ATP6V1G2-DDX39B, CAPRIN1, GIGYF1 (+19 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CSMD1	0	—
STXBP1	1	—
ZMIZ1	0	—
DIP2A	0	—
WDFY3	0	—
CNTN4	0	—
CORO1A	12	—
CYCSP5	0	—
TM9SF4	1	—
ATP6V1G2-DDX39B	0	—
CAPRIN1	2	—
GIGYF1	0	—
RERE	0	—
RFX3	0	—
SLC7A3	1	—
VEZF1	0	—
CTTNBP2	0	—
ASTN2	0	—
ZC3H12B	0	—
ADGRG4	0	—
RIT2	0	—
TRIM38	0	—
TRIM39	0	—
RNF5	2	—
SNORD48	0	—
SNORD52	0	—
CNNM2	0	—
SATB1	0	—
SBF1	0	—
SEC13	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,517.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	836
PHASE2	135
PHASE1	44
PHASE4	21
PHASE3	21
PHASE1/PHASE2	16
EARLY_PHASE1	15
PHASE2/PHASE3	12

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT05268796	PHASE2/PHASE3	RECRUITING	Telehealth-Enabled Versus In-Person Parent-Mediated Behavioral Treatment for Challenging Behaviors in Children With ASD
NCT05494398	PHASE2/PHASE3	ENROLLING_BY_INVITATION	Targeting the Neurobiology of RRB in Autism Using N-acetylcysteine: Open Label
NCT05664789	PHASE2/PHASE3	RECRUITING	Targeting the Neurobiology of RRB in Autism Using N-acetylcysteine: Trial
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT07257939	PHASE3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder
NCT07450443	PHASE2/PHASE3	RECRUITING	Role of the Gut Vascular Barrier and Microbiota in Autism Spectrum Disorders
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02007447	PHASE2/PHASE3	TERMINATED	Oxytocin in Adolescents With Autism Spectrum Disorders
NCT02212275	PHASE2/PHASE3	WITHDRAWN	Cortical Metrics in Intervention Trials With Autism Spectrum Disorders
NCT02757066	PHASE2/PHASE3	COMPLETED	Verification of the Efficacy of NPC-15 for Sleep Disorders of Children With Autism Spectrum Disorders
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03204786	PHASE2/PHASE3	COMPLETED	Intranasal Vasopressin Treatment in Children With Autism
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARIPRAZINE	4	6
BUSPIRONE	4	5
BUMETANIDE	4	4
MEMANTINE	4	4
AMITRIPTYLINE	4	3
PYRIDOXINE	4	3
RILUZOLE	4	3
LEVOLEUCOVORIN CALCIUM	4	2
METFORMIN	4	2
OXYTOCIN	4	2
POLYETHYLENE GLYCOL 3350	4	2
VASOPRESSIN	4	2
ACAMPROSATE	4	1
ACETYLCYSTEINE	4	1
AMPHETAMINE	4	1
ARIPIPRAZOLE	4	1
BACLOFEN	4	1
BETAHISTINE	4	1
CITALOPRAM	4	1
CITALOPRAM HYDROBROMIDE	4	1
CLOBAZAM	4	1
CLONIDINE	4	1
DIPHENHYDRAMINE	4	1
DIVALPROEX SODIUM	4	1
ESKETAMINE	4	1
FERRIC CARBOXYMALTOSE	4	1
FERROUS SULFATE	4	1
GABAPENTIN	4	1
GLYCERIN	4	1
LISDEXAMFETAMINE DIMESYLATE	4	1