Schizophrenia

Summary

Schizophrenia (MONDO:0005090) is a disease (an umbrella term covering 18 Mondo subtypes) with 39 cohort genes (5,595 GWAS associations across 259 studies) and 2,957 clinical trials. The dominant Reactome pathway is Butyrophilin (BTN) family interactions (7 cohort genes). Top therapeutic interventions include ziprasidone, olanzapine, and risperidone.

At a glance

• Umbrella term: 18 Mondo subtypes
• Cohort genes: 39
• GWAS associations: 5,595
• ClinVar variants: 351
• Clinical trials: 2,957

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	schizophrenia
Mondo ID	MONDO:0005090
OMIM	181500
Orphanet	3140
DOID	DOID:5419
ICD-10-CM	F20
ICD-11	1683919430
NCIT	C3362
SNOMED CT	58214004
UMLS	C0036341
MedGen	48574
Is cancer (heuristic)	no

Also known as: schizophrenia · schizophrenia (disease) · schizophrenia 12 · SCZD

Data availability: 351 ClinVar variants · 5,595 GWAS associations (259 studies) · 90 GenCC gene-disease records · 1 HPO phenotype · 134 cell lines.

Disease family

An umbrella term covering 18 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › cognitive disorder › psychotic disorder › schizophrenia

Related subtypes (7): schizophreniform disorder, alcoholic psychosis, delusional disorder, substance-induced psychosis, methamphetamine-induced psychosis, schizoaffective disorder, postpartum psychosis

Subtypes (18): paranoid schizophrenia, treatment-refractory schizophrenia, schizophrenia 1, schizophrenia 3, schizophrenia 5, schizophrenia 7, schizophrenia 8, schizophrenia 2, schizophrenia 10, schizophrenia 11, schizophrenia 12, schizophrenia 15, schizophrenia 16, chromosome 2p16.3 deletion syndrome, early-onset schizophrenia, schizophrenia 19, schizophrenia 17, childhood-onset schizophrenia

Genetics & variants

GWAS landscape

5,595 GWAS associations across 259 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs115329265	3e-31	RPSAP2 - NOP56P1	A	1.21
rs13217619	2e-29	ZSCAN31	T	1.25
rs144447022	2e-28	LINC03003	G	1.25
rs34706883	5e-27	H2AC15	A	1.24
rs41266839	7e-27	BTN3A1	G	1.25
rs55834529	9e-27	VN1R11P - RNU2-62P	A	1.24
rs116137698	3e-26	LINC00533	A	1.22
rs13198474	3e-20	SLC17A3	G	1.22
rs2596500	8e-20	LINC02571 - HLA-B	A	1.18
rs114200269	2e-19	UBQLN1P1 - MICC	T	1.23
rs1702294	3e-19	MIR137HG	C	1.13
rs9467711	3e-19	H3C9P - BTN3A2	A	1.16
rs11191419	6e-19	PTGES3P4 - BORCS7	T	1.1
rs9274623	6e-19	HLA-DQB1	G	1.14
rs67682613	7e-19	NEU1	G	1.15
rs2007044	3e-18	CACNA1C	G	1.1
rs2660304	1e-17	MIR137HG	T	1.12
rs144762289	3e-17	HCG27 - HLA-C	?	1.16
rs187696124	7e-17	HLA-DRB9	T	1.14
rs2523722	1e-16	TRIM26	G	1.25
rs10883832	2e-16	NT5C2	T	1.16
rs114882497	2e-16	TSBP1-AS1 - HLA-DRA	T	1.13
rs202906	3e-16	ZSCAN16-AS1	T	1.13
rs13212562	3e-16	VN1R10P - ZNF204P	A	1.14
rs73396800	4e-16	HLA-DMB - HLA-DMA	G	1.19
rs144373461	6e-16	HLA-F-AS1	C	1.15
rs4129585	2e-15	TSNARE1	A	1.09
rs114904464	3e-15	FGFR3P1 - ZDHHC20P2	?	1.14
rs145547914	3e-15	NOTCH4 - TSBP1-AS1	?	1.12
rs13217239	4e-15	POM121L2	T	1.09

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002539	Ripke S	2014	32,405	42,221	Biological insights from 108 schizophrenia-associated genetic loci.
GCST001851	Aberg KA	2013	11,185	10,768	A comprehensive family-based replication study of schizophrenia genes.
GCST004252	McLaughlin RL	2017	10,147	22,094	Genetic correlation between amyotrophic lateral sclerosis and schizophrenia.
GCST001242	Ripke S	2011	9,394	12,462	Genome-wide association study identifies five new schizophrenia loci.
GCST001877	Smoller JW	2013	6,990	27,888	Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
GCST004521	Anney RJL	2017	6,197	7,377	Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.
GCST002149	Ripke S	2013	5,001	6,243	Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
GCST002295	Ruderfer DM	2013	4,528	11,637	Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.
GCST003880	Yu H	2016	4,384	5,770	Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.
GCST001301	Shi Y	2011	3,750	6,468	Common variants on 8p12 and 1q24.2 confer risk of schizophrenia.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	3
Tier 3: regulatory	0
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	38
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	12

Functional consequences

Consequence	Count
intron_variant	34
intergenic_variant	12
3_prime_UTR_variant	2
missense_variant	1
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs115329265	6	28744470		0.15	intron_variant	RPSAP2 - NOP56P1	3e-31	Tier 4: intronic/intergenic
rs13217619	6	28338894	T>C	0.05	intron_variant	ZSCAN31	2e-29	Tier 4: intronic/intergenic
rs144447022	6	29276442	G>C,T	0.05	intron_variant	LINC03003	2e-28	Tier 4: intronic/intergenic
rs34706883	6	27837477	A>C,T	0.05	intergenic_variant	H2AC15	5e-27	Tier 4: intronic/intergenic
rs41266839	6	26409662	G>A,C	0.05	missense_variant	BTN3A1	7e-27	Tier 1: coding
rs55834529	6	27104763	A>G	0.05	intergenic_variant	VN1R11P - RNU2-62P	9e-27	Tier 4: intronic/intergenic
rs116137698	6	28699892			intron_variant	LINC00533	3e-26	Tier 4: intronic/intergenic
rs13198474	6	25874195	G>A,T	0.05	5_prime_UTR_variant	SLC17A3	3e-20	Tier 2: splice/UTR
rs2596500	6	31353490	A>C,G	0.05	intron_variant	LINC02571 - HLA-B	8e-20	Tier 4: intronic/intergenic
rs114200269	6	30368886			intergenic_variant	UBQLN1P1 - MICC	2e-19	Tier 4: intronic/intergenic
rs1702294	1	98036428	T>A,C,G	0.191	intron_variant	MIR137HG	3e-19	Tier 4: intronic/intergenic
rs9467711	6	26332377	A>C	0.05	intron_variant	H3C9P - BTN3A2	3e-19	Tier 4: intronic/intergenic
rs11191419	10	102852578	T>A,C	0.36	intron_variant	PTGES3P4 - BORCS7	6e-19	Tier 4: intronic/intergenic
rs9274623	6	32668221	G>C,T	0.05	intergenic_variant	HLA-DQB1	6e-19	Tier 4: intronic/intergenic
rs67682613	6	31858928			3_prime_UTR_variant	NEU1	7e-19	Tier 2: splice/UTR
rs2007044	12	2235794	A>G	0.376	intron_variant	CACNA1C	3e-18	Tier 4: intronic/intergenic
rs2660304	1	98046571	G>A,C,T	0.05	intergenic_variant	MIR137HG	1e-17	Tier 4: intronic/intergenic
rs144762289	6	31229085			intergenic_variant	HCG27 - HLA-C	3e-17	Tier 4: intronic/intergenic
rs187696124	6	32469754			intron_variant	HLA-DRB9	7e-17	Tier 4: intronic/intergenic
rs2523722	6	30197496	C>A,G,T	0.263	intron_variant	TRIM26	1e-16	Tier 4: intronic/intergenic
rs10883832	10	103111522	T>A,G	0.05	intron_variant	NT5C2	2e-16	Tier 4: intronic/intergenic
rs114882497	6	32423415			intron_variant	TSBP1-AS1 - HLA-DRA	2e-16	Tier 4: intronic/intergenic
rs202906	6	28043874	T>A,C,G	0.05	intron_variant	ZSCAN16-AS1	3e-16	Tier 4: intronic/intergenic
rs13212562	6	27332531	A>G	0.05	intergenic_variant	VN1R10P - ZNF204P	3e-16	Tier 4: intronic/intergenic
rs73396800	6	32946949	G>C,T	0.05	intron_variant	HLA-DMB - HLA-DMA	4e-16	Tier 4: intronic/intergenic
rs144373461	6	29783228			intron_variant	HLA-F-AS1	6e-16	Tier 4: intronic/intergenic
rs4129585	8	142231572	A>C,G,T	0.424	intron_variant	TSNARE1	2e-15	Tier 4: intronic/intergenic
rs114904464	6	31380300			intron_variant	FGFR3P1 - ZDHHC20P2	3e-15	Tier 4: intronic/intergenic
rs145547914	6	32238466			intergenic_variant	NOTCH4 - TSBP1-AS1	3e-15	Tier 4: intronic/intergenic
rs13217239	6	27287188	T>C	0.05	intergenic_variant	POM121L2	4e-15	Tier 4: intronic/intergenic

ClinVar germline variants

351 retrieved; paginated sample, class counts are floors:

141 likely pathogenic, 106 uncertain significance, 55 pathogenic, 13 pathogenic/likely pathogenic, 13 conflicting classifications of pathogenicity, 10 benign, 4 not provided, 4 benign/likely benign, 2 risk factor, 1 uncertain risk allele, 1 benign/likely benign; other, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
545220	NC_000017.11:g.(?36357256)(37995300_?)del	AATF	Pathogenic	criteria provided, single submitter
545186	NC_000016.10:g.(?14780667)(16415941_?)del	ABCC1	Pathogenic	criteria provided, single submitter
545187	Single allele	ABCC1	Pathogenic	criteria provided, single submitter
545188	Single allele	ABCC1	Pathogenic	criteria provided, single submitter
545189	Single allele	ABCC1	Pathogenic	criteria provided, single submitter
545190	Single allele	ABCC1	Pathogenic	criteria provided, single submitter
545191	Single allele	ABCC1	Pathogenic	criteria provided, single submitter
545192	NC_000016.10:g.(?15328439)(16443962_?)del	ABCC1	Pathogenic	criteria provided, single submitter
545256	NC_000022.11:g.(?18159879)(21362822_?)del	AIFM3	Pathogenic	criteria provided, single submitter
545257	NC_000022.11:g.(?18159879)(21387988_?)del	AIFM3	Pathogenic	criteria provided, single submitter
545258	NC_000022.11:g.(?18163926)(21277123_?)del	AIFM3	Pathogenic	criteria provided, single submitter
545259	NC_000022.11:g.(?18802709)(21343709_?)del	AIFM3	Pathogenic	criteria provided, single submitter
545260	NC_000022.11:g.(?18832909)(21123588_?)del	AIFM3	Pathogenic	criteria provided, single submitter
545261	NC_000022.11:g.(?18846939)(21221413_?)del	AIFM3	Pathogenic	criteria provided, single submitter
545263	NC_000022.11:g.(?18880919)(21123588_?)del	AIFM3	Pathogenic	criteria provided, single submitter
545200	Single allele	ALDOA	Pathogenic	criteria provided, single submitter
545202	Single allele	ALDOA	Pathogenic	criteria provided, single submitter
545203	NC_000016.10:g.(?29627836)(30184960_?)del	ALDOA	Pathogenic	criteria provided, single submitter
545204	Single allele	ALDOA	Pathogenic	criteria provided, single submitter
545205	Single allele	ALDOA	Pathogenic	criteria provided, single submitter
545143	NC_000001.11:g.(?145430995)(148427734_?)del	ANKRD35-DT	Pathogenic	criteria provided, single submitter
545197	NC_000016.10:g.(?28351819)(29325073_?)del	APOBR	Pathogenic	criteria provided, single submitter
488014	Single allele	ARAF	Pathogenic	criteria provided, single submitter
545177	NC_000015.10:g.(?30325774)(32194551_?)del	ARHGAP11B	Pathogenic	criteria provided, single submitter
1330206	GRCh37/hg19 22q11.21(chr22:19036286-21208284)x1	ARVCF	Pathogenic	criteria provided, single submitter
545262	NC_000022.11:g.(?18880919)(20346734_?)del	ARVCF	Pathogenic	criteria provided, single submitter
545294	NC_000003.12:g.(?195990063)(197617301_?)del	BDH1	Pathogenic	criteria provided, single submitter
545295	NC_000003.12:g.(?196154147)(197376501_?)del	CEP19	Pathogenic	criteria provided, single submitter
545167	NC_000015.10:g.(?22673675)(23126124_?)del	CYFIP1	Pathogenic	criteria provided, single submitter
545168	NC_000015.10:g.(?22681827)(23226874_?)del	CYFIP1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 85 · Orphanet: 49 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 13

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

Gene	HGNC	Evidence routes
SLC12A2	SLC12A2	GWAS, GenCC, Orphanet
CACNA1C	CACNA1C	GWAS, Orphanet
CSMD1	CSMD1	GWAS
ZDHHC5	ZDHHC5	GWAS, GenCC
ZNF804A	ZNF804A	GWAS
CTNNA1	CTNNA1	GWAS, Orphanet
ZDBF2	ZDBF2	GWAS, GenCC
DRD2	DRD2	GWAS, Orphanet
ALDOA	ALDOA	GWAS, Orphanet
KIT	KIT	GWAS, Orphanet
LRP1	LRP1	GWAS, GenCC, Orphanet
MECP2	MECP2	GWAS, Orphanet
RELN	RELN	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
ABCA13	Limited	Unknown	schizophrenia
ARFGEF1	Limited	Unknown	schizophrenia	6
DNAH9	Limited	Autosomal dominant	schizophrenia	7
DRD3	Limited	Autosomal dominant	schizophrenia	2
GET1	Limited	Unknown	schizophrenia	4
LRP1	Limited	Unknown	schizophrenia	7
NRXN1	Limited	Unknown	schizophrenia	7
SLC4A8	Limited	Unknown	schizophrenia
SMARCA1	Limited	Unknown	schizophrenia	3
SPAG9	Limited	Autosomal dominant	schizophrenia
ST8SIA2	Limited	Autosomal dominant	schizophrenia
ZDHHC5	Limited	Unknown	schizophrenia
ANAPC5	No Known Disease Relationship	Unknown	schizophrenia
ARHGEF15	No Known Disease Relationship	Unknown	schizophrenia	2
CBX8	No Known Disease Relationship	Unknown	schizophrenia
CHI3L1	No Known Disease Relationship	Unknown	schizophrenia
FAXDC2	No Known Disease Relationship	Unknown	schizophrenia
PAQR8	No Known Disease Relationship	Unknown	schizophrenia
RELT	No Known Disease Relationship	Unknown	schizophrenia	5
SELENBP1	No Known Disease Relationship	Unknown	schizophrenia	4
SHOX2	No Known Disease Relationship	Unknown	schizophrenia	2
SLC12A2	No Known Disease Relationship	Unknown	schizophrenia	8
SLC18A2	No Known Disease Relationship	Unknown	schizophrenia	6
SYNGR1	No Known Disease Relationship	Unknown	schizophrenia	2
TAF9	No Known Disease Relationship	Unknown	schizophrenia
TBXA2R	No Known Disease Relationship	Unknown	schizophrenia	4
UTRN	No Known Disease Relationship	Unknown	schizophrenia
ZDBF2	No Known Disease Relationship	Unknown	schizophrenia	2
ZNF229	No Known Disease Relationship	Unknown	schizophrenia
ZP4	No Known Disease Relationship	Unknown	schizophrenia

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC12A2	Orphanet:633021	SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2	Orphanet:633024	SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome
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
CTNNA1	Orphanet:26106	Hereditary diffuse gastric cancer
CTNNA1	Orphanet:99001	Butterfly-shaped pigment dystrophy
DNAH9	Orphanet:101063	Situs inversus totalis
DNAH9	Orphanet:157769	Situs ambiguus
DNAH9	Orphanet:244	Primary ciliary dyskinesia
DRD2	Orphanet:36899	Myoclonus-dystonia syndrome
ALDOA	Orphanet:57	Glycogen storage disease due to aldolase A deficiency
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans
KIT	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
KIT	Orphanet:98834	Acute myeloblastic leukemia with maturation
KIT	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
LRP1	Orphanet:2340	Keratosis follicularis spinulosa decalvans
LRP1	Orphanet:79100	Atrophoderma vermiculata
MECP2	Orphanet:1762	Proximal Xq28 duplication syndrome
MECP2	Orphanet:209370	MECP2-related severe neonatal encephalopathy
MECP2	Orphanet:3077	X-linked intellectual disability-psychosis-macroorchidism syndrome
MECP2	Orphanet:3095	Atypical Rett syndrome
MECP2	Orphanet:536	Systemic lupus erythematosus
MECP2	Orphanet:777	X-linked non-syndromic intellectual disability
MECP2	Orphanet:778	Rett syndrome
NRXN1	Orphanet:600663	NRXN1-related severe neurodevelopmental disorder-motor stereotypies-chronic constipation-sleep-wake cycle disturbance
RELN	Orphanet:101046	Epilepsy with auditory features
RELN	Orphanet:89844	Lissencephaly syndrome, Norman-Roberts type
SELENBP1	Orphanet:562538	Autosomal recessive extra-oral halitosis
SLC18A2	Orphanet:352649	Brain dopamine-serotonin vesicular transport disease
TBXA2R	Orphanet:220443	Bleeding diathesis due to thromboxane synthesis deficiency
RELT	Orphanet:100032	Hypocalcified amelogenesis imperfecta

Cohort genes → proteins

39 cohort genes, 39 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_and_gencc	4
gwas_and_clinvar	9
multi_evidence	26

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	gwas,gencc
SYNGR1	HGNC:11498	ENSG00000100321	O43759	Synaptogyrin-1	gencc,clinvar
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	gwas,clinvar
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas,clinvar
ABCA13	HGNC:14638	ENSG00000179869	Q86UQ4	ATP-binding cassette sub-family A member 13	gencc,clinvar
ZDHHC5	HGNC:18472	ENSG00000156599	Q9C0B5	Palmitoyltransferase ZDHHC5	gwas,gencc
CHI3L1	HGNC:1932	ENSG00000133048	P36222	Chitinase-3-like protein 1	gencc,clinvar
ZNF804A	HGNC:21711	ENSG00000170396	Q7Z570	Zinc finger protein 804A	gwas,clinvar
CTNNA1	HGNC:2509	ENSG00000044115	P35221	Catenin alpha-1	gwas,clinvar
ZDBF2	HGNC:29313	ENSG00000204186	Q9HCK1	DBF4-type zinc finger-containing protein 2	gwas,gencc
DNAH9	HGNC:2953	ENSG00000007174	Q9NYC9	Dynein axonemal heavy chain 9	gencc,clinvar
DRD2	HGNC:3023	ENSG00000149295	P14416	D(2) dopamine receptor	gwas,clinvar
DRD3	HGNC:3024	ENSG00000151577	P35462	D(3) dopamine receptor	gencc,clinvar
ALDOA	HGNC:414	ENSG00000149925	P04075	Fructose-bisphosphate aldolase A	gwas,clinvar
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	gwas,clinvar
LRP1	HGNC:6692	ENSG00000123384	Q07954	Prolow-density lipoprotein receptor-related protein 1	gwas,gencc
MECP2	HGNC:6990	ENSG00000169057	P51608	Methyl-CpG-binding protein 2	gwas,clinvar
NRXN1	HGNC:8008	ENSG00000179915	P58400	Neurexin-1-beta	gencc,clinvar
RELN	HGNC:9957	ENSG00000189056	P78509	Reelin	gwas,clinvar
SELENBP1	HGNC:10719	ENSG00000143416	Q13228	Methanethiol oxidase	gencc
SHOX2	HGNC:10854	ENSG00000168779	O60902	Short stature homeobox protein 2	gencc
ST8SIA2	HGNC:10870	ENSG00000140557	Q92186	Alpha-2,8-sialyltransferase 8B	gencc
SLC18A2	HGNC:10935	ENSG00000165646	Q05940	Synaptic vesicular amine transporter	gencc
SLC4A8	HGNC:11034	ENSG00000050438	Q2Y0W8	Electroneutral sodium bicarbonate exchanger 1	gencc
SMARCA1	HGNC:11097	ENSG00000102038	P28370	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 1	gencc
TAF9	HGNC:11542	ENSG00000273841	Q16594	Transcription initiation factor TFIID subunit 9	gencc
TBXA2R	HGNC:11608	ENSG00000006638	P21731	Thromboxane A2 receptor	gencc
UTRN	HGNC:12635	ENSG00000152818	P46939	Utrophin	gencc
GET1	HGNC:12790	ENSG00000182093	O00258	Guided entry of tail-anchored proteins factor 1	gencc
ZNF229	HGNC:13022	ENSG00000278318	Q9UJW7	Zinc finger protein 229	gencc
FAXDC2	HGNC:1334	ENSG00000170271	Q96IV6	Fatty acid hydroxylase domain-containing protein 2	gencc
RELT	HGNC:13764	ENSG00000054967	Q969Z4	Tumor necrosis factor receptor superfamily member 19L	gencc
SPAG9	HGNC:14524	ENSG00000008294	O60271	C-Jun-amino-terminal kinase-interacting protein 4	gencc
ARHGEF15	HGNC:15590	ENSG00000198844	O94989	Rho guanine nucleotide exchange factor 15	gencc
PAQR8	HGNC:15708	ENSG00000170915	Q8TEZ7	Membrane progestin receptor beta	gencc
ANAPC5	HGNC:15713	ENSG00000089053	Q9UJX4	Anaphase-promoting complex subunit 5	gencc
ZP4	HGNC:15770	ENSG00000116996	Q12836	Zona pellucida sperm-binding protein 4	gencc
ARFGEF1	HGNC:15772	ENSG00000066777	Q9Y6D6	Brefeldin A-inhibited guanine nucleotide-exchange protein 1	gencc
CBX8	HGNC:15962	ENSG00000141570	Q9HC52	Chromobox protein homolog 8	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
SYNGR1	Synaptogyrin-1	May play a role in regulated exocytosis.
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.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
ABCA13	ATP-binding cassette sub-family A member 13	May mediate the cholesterol and gangliosides transport from the plasma membrane to intracellular vesicles in an ATP hydrolysis dependent manner, thus playing a role in their internalization by endocytic retrograde transport and may also pa…
ZDHHC5	Palmitoyltransferase ZDHHC5	Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflam…
CHI3L1	Chitinase-3-like protein 1	Carbohydrate-binding lectin with a preference for chitin.
CTNNA1	Catenin alpha-1	Associates with the cytoplasmic domain of a variety of cadherins.
DNAH9	Dynein axonemal heavy chain 9	Force generating protein required for cilia beating in respiratory epithelia.
DRD2	D(2) dopamine receptor	Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
DRD3	D(3) dopamine receptor	Dopamine receptor that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions.
ALDOA	Fructose-bisphosphate aldolase A	Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
LRP1	Prolow-density lipoprotein receptor-related protein 1	Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells.
MECP2	Methyl-CpG-binding protein 2	Chromosomal protein that binds to methylated DNA.
NRXN1	Neurexin-1-beta	Neuronal cell surface protein involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins.
RELN	Reelin	Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment.
SELENBP1	Methanethiol oxidase	Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria.
SHOX2	Short stature homeobox protein 2	May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation.
ST8SIA2	Alpha-2,8-sialyltransferase 8B	Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan acceptor through alpha-2,8-linkages.
SLC18A2	Synaptic vesicular amine transporter	Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles.
SLC4A8	Electroneutral sodium bicarbonate exchanger 1	Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1.
SMARCA1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 1	ATPase that possesses intrinsic ATP-dependent chromatin-remodeling activity.
TAF9	Transcription initiation factor TFIID subunit 9	The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.
TBXA2R	Thromboxane A2 receptor	Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation.
UTRN	Utrophin	May play a role in anchoring the cytoskeleton to the plasma membrane.
GET1	Guided entry of tail-anchored proteins factor 1	Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER).
ZNF229	Zinc finger protein 229	May be involved in transcriptional regulation.
FAXDC2	Fatty acid hydroxylase domain-containing protein 2	Promotes megakaryocyte differentiation by enhancing ERK phosphorylation and up-regulating RUNX1 expression.
RELT	Tumor necrosis factor receptor superfamily member 19L	May play a role in apoptosis.
SPAG9	C-Jun-amino-terminal kinase-interacting protein 4	The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module.
ARHGEF15	Rho guanine nucleotide exchange factor 15	Guanine nucleotide exchange factor (GEF) that activates RhoA, playing a role in the regulation of actin cytoskeleton organization.
PAQR8	Membrane progestin receptor beta	Plasma membrane progesterone (P4) receptor coupled to G proteins.
ANAPC5	Anaphase-promoting complex subunit 5	Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
ZP4	Zona pellucida sperm-binding protein 4	Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.
ARFGEF1	Brefeldin A-inhibited guanine nucleotide-exchange protein 1	Promotes guanine-nucleotide exchange on ARF1 and ARF3.
CBX8	Chromobox protein homolog 8	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.

Protein-family classification

Druggable: 12 · Difficult: 7 · Unknown: 20 · 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	1	6.9×	0.664
Transporter	2	4.0×	0.664
Ion channel	1	2.9×	0.664
GPCR	3	1.8×	0.664
Transcription factor	6	1.3×	0.664
Other/Unknown	20	0.9×	0.854
Enzyme (other)	3	0.9×	0.854
Antibody/Immunoglobulin	1	0.8×	0.854
Kinase	1	0.7×	0.854
Scaffold/PPI	1	0.4×	0.902

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom
SYNGR1	Other/Unknown	no		Marvel, Synaptogyrin
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
ABCA13	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
ZDHHC5	Enzyme (other)	yes	2.3.1.225	Palmitoyltrfase_DHHC
CHI3L1	Other/Unknown	no		Glyco_hydro18_cat, Chitinase_II/V-like_cat, GH_hydrolase_sf
ZNF804A	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, ZNF804A-like/GPATCH8
CTNNA1	Other/Unknown	no		Vinculin_CS, Alpha_catenin, Vinculin/catenin
ZDBF2	Transcription factor	no		Znf_DBF, Znf_DBF_sf, ZDBF2
DNAH9	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DRD2	GPCR	yes		GPCR_Rhodpsn, Dopamine_rcpt, Dopamine_D2_rcpt
DRD3	GPCR	yes		GPCR_Rhodpsn, Dopamine_rcpt, Dopamine_D3_rcpt
ALDOA	Enzyme (other)	yes	4.1.2.13	FBA_I, Aldolase_TIM, Aldolase_I_AS
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
LRP1	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
MECP2	Other/Unknown	no		Methyl_CpG_DNA-bd, DNA-bd_dom_sf, Me_CpG-bd_MeCP2
NRXN1	Other/Unknown	no		Laminin_G, Neurexin-like, ConA-like_dom_sf
RELN	Other/Unknown	no		EGF, Reeler_dom, EGF_extracell
SELENBP1	Other/Unknown	no		Se-bd
SHOX2	Transcription factor	no		HTH_motif, HD, OAR_dom
ST8SIA2	Enzyme (other)	yes	2.4.99.8	Glyco_trans_29, Sialyl_trans, GT29-like_sf
SLC18A2	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
SLC4A8	Other/Unknown	no		HCO3_transpt_euk, Na/HCO3_transpt, HCO3_transpt-like_TM_dom
SMARCA1	Transcription factor	no		SNF2_N, SANT/Myb, Helicase_C-like
TAF9	Other/Unknown	no		TFIID-31, Histone-fold, TFIID_subunit_9/TAF9
TBXA2R	GPCR	yes		GPCR_Rhodpsn, Thbox_rcpt, Prostanoid_rcpt
UTRN	Transcription factor	no		Znf_ZZ, WW_dom, Actinin_actin-bd_CS
GET1	Other/Unknown	no		Get1, Helix_hairpin_bin_sf
ZNF229	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
FAXDC2	Other/Unknown	no		Fatty_acid_hydroxylase, Sterol_desaturase-rel
RELT	Other/Unknown	no		TNF_rcpt_RELT, TNFR_19-like, TNFRSF19L_N
SPAG9	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, JIP_LZII, RH1
ARHGEF15	Other/Unknown	no		DH_dom, PH-like_dom_sf, DBL_dom_sf
PAQR8	Other/Unknown	no		AdipoR/HlyIII-related
ANAPC5	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, Apc5_dom
ZP4	Antibody/Immunoglobulin	yes		P_trefoil_dom, ZP_dom, P_trefoil_CS
ARFGEF1	Other/Unknown	no		Sec7_dom, ARM-like, Mon2/Sec7/BIG1-like_HDS
CBX8	Other/Unknown	no		Chromo/chromo_shadow_dom, Chromo-like_dom_sf, Chromodomain_CS

Expression context

Cohort genes with no expression data: 0.

34 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)	38
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	4
male germ line stem cell (sensu Vertebrata) in testis	4
secondary oocyte	4
inferior vagus X ganglion	3
Brodmann (1909) area 10	3
Brodmann (1909) area 23	3
ganglionic eminence	3
calcaneal tendon	3
adrenal tissue	3
right uterine tube	3
sural nerve	3
primordial germ cell in gonad	3
apex of heart	2
middle temporal gyrus	2
epithelium of nasopharynx	2
ileal mucosa	2
epithelium of bronchus	2
lateral nuclear group of thalamus	2
oocyte	2
stromal cell of endometrium	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC12A2	277	ubiquitous	marker	palpebral conjunctiva, parotid gland, inferior vagus X ganglion
SYNGR1	298	ubiquitous	marker	Brodmann (1909) area 10, right hemisphere of cerebellum, cerebellar hemisphere
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
ABCA13	126	broad	marker	bronchial epithelial cell, bronchus, epithelium of nasopharynx
ZDHHC5	257	ubiquitous	marker	esophagus squamous epithelium, gingival epithelium, ileal mucosa
CHI3L1	271	ubiquitous	marker	pericardium, cartilage tissue, upper leg skin
ZNF804A	144	broad	marker	ganglionic eminence, Brodmann (1909) area 10, Brodmann (1909) area 23
CTNNA1	305	ubiquitous	marker	colonic epithelium, calcaneal tendon, amniotic fluid
ZDBF2	134	ubiquitous	yes	adrenal tissue, male germ line stem cell (sensu Vertebrata) in testis, corpus callosum
DNAH9	184	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
DRD2	159	broad	yes	putamen, nucleus accumbens, male germ line stem cell (sensu Vertebrata) in testis
DRD3	25		marker	male germ line stem cell (sensu Vertebrata) in testis, metanephric glomerulus, endometrium epithelium
ALDOA	134	ubiquitous	marker	skeletal muscle tissue, gastrocnemius, hindlimb stylopod muscle
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
LRP1	293	ubiquitous	marker	stromal cell of endometrium, descending thoracic aorta, ascending aorta
MECP2	277	ubiquitous	marker	paraflocculus, Brodmann (1909) area 10, sural nerve
NRXN1	222	broad	marker	sural nerve, cortical plate, middle temporal gyrus
RELN	254	broad	marker	olfactory bulb, cerebellar vermis, cerebellum
SELENBP1	281	ubiquitous	marker	mucosa of transverse colon, rectum, colonic mucosa
SHOX2	167	broad	marker	buccal mucosa cell, lateral nuclear group of thalamus, saphenous vein
ST8SIA2	98	broad	marker	cortical plate, ganglionic eminence, ventricular zone
SLC18A2	191	broad	marker	substantia nigra pars reticulata, substantia nigra pars compacta, secondary oocyte
SLC4A8	219	ubiquitous	marker	pons, Brodmann (1909) area 23, superior vestibular nucleus
SMARCA1	286	ubiquitous	marker	adrenal tissue, choroid plexus epithelium, tibia
TAF9	144	broad	marker	left testis, right testis, testis
TBXA2R	241	ubiquitous	yes	tendon of biceps brachii, type B pancreatic cell, olfactory bulb
UTRN	272	ubiquitous	marker	calcaneal tendon, tendon, sural nerve
GET1	292	ubiquitous	marker	bronchial epithelial cell, substantia nigra pars compacta, epithelium of bronchus
ZNF229	168	ubiquitous	yes	primordial germ cell in gonad, adrenal tissue, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIT	6,087
MECP2	5,688
SMARCA1	4,447
ALDOA	3,591
DRD2	3,148
CACNA1C	3,145
CTNNA1	3,128
LRP1	2,662
ZDHHC5	2,548
ANAPC5	2,532

Intra-cohort edges

A	B	Sources
ALDOA	ZP4	intact
CACNA1C	CSMD1	string_interaction
CACNA1C	SLC4A8	intact
CACNA1C	ZNF804A	string_interaction
CSMD1	ZNF804A	string_interaction
DRD2	SLC18A2	string_interaction
DRD2	ZNF804A	string_interaction
DRD3	SELENBP1	biogrid_interaction
SLC12A2	SLC4A8	string_interaction

Structural data

PDB: 25 · AlphaFold-only: 14 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIT	P10721	52
CACNA1C	Q13936	33
SLC18A2	Q05940	32
TAF9	Q16594	31
ANAPC5	Q9UJX4	20
SLC12A2	P55011	14
CHI3L1	P36222	13
DRD2	P14416	11
CTNNA1	P35221	10
MECP2	P51608	9
ALDOA	P04075	8
DRD3	P35462	7
LRP1	Q07954	7
TBXA2R	P21731	6
GET1	O00258	4
NRXN1	P58400	3
UTRN	P46939	3
ARFGEF1	Q9Y6D6	3
CBX8	Q9HC52	3
SYNGR1	O43759	1
CSMD1	Q96PZ7	1
DNAH9	Q9NYC9	1
RELN	P78509	1
SLC4A8	Q2Y0W8	1
SPAG9	O60271	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SELENBP1	Q13228	96.85
PAQR8	Q8TEZ7	93.25
FAXDC2	Q96IV6	92.28
ST8SIA2	Q92186	85.70
SMARCA1	P28370	75.48
ZP4	Q12836	74.90
RELT	Q969Z4	63.38
ARHGEF15	O94989	62.96
ZNF229	Q9UJW7	62.77
SHOX2	O60902	61.50
ZDHHC5	Q9C0B5	59.32
ZNF804A	Q7Z570	45.51
ZDBF2	Q9HCK1	34.79
ABCA13	Q86UQ4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 690. Enrichment computed across 250 evidence-associated genes (168 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 168 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	36.6×	1e-07	BTN1A1, BTN2A1, BTN2A2, BTN3A1, BTN3A2, BTN3A3, BTNL2
Activation of C3 and C5	3	22.7×	0.085	CFB, C2, C4A
Defective TBXAS1 causes GHDD	1	68.0×	0.267	TBXAS1
Defective SLC2A9 causes hypouricemia renal 2 (RHUC2)	1	68.0×	0.267	SLC2A9
Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	68.0×	0.267	SLC6A3
Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	68.0×	0.267	SLC6A3
Loss of MECP2 binding ability to 5hmC-DNA	1	68.0×	0.267	MECP2
Dasatinib-resistant KIT mutants	1	68.0×	0.267	KIT
Imatinib-resistant KIT mutants	1	68.0×	0.267	KIT
KIT mutants bind TKIs	1	68.0×	0.267	KIT
Masitinib-resistant KIT mutants	1	68.0×	0.267	KIT
Nilotinib-resistant KIT mutants	1	68.0×	0.267	KIT
Regorafenib-resistant KIT mutants	1	68.0×	0.267	KIT
Signaling by kinase domain mutants of KIT	1	68.0×	0.267	KIT
Sunitinib-resistant KIT mutants	1	68.0×	0.267	KIT
Signaling by juxtamembrane domain KIT mutants	1	68.0×	0.267	KIT
Sorafenib-resistant KIT mutants	1	68.0×	0.267	KIT
Drug resistance of KIT mutants	1	68.0×	0.267	KIT
Signaling by extracellular domain mutants of KIT	1	68.0×	0.267	KIT
Dopamine receptors	2	27.2×	0.267	DRD2, DRD3
Regulation of cortical dendrite branching	2	27.2×	0.267	ROBO1, ROBO2
Cation-coupled Chloride cotransporters	2	19.4×	0.267	SLC12A2, SLC12A4
Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)	2	15.1×	0.267	SREBF1, SREBF2
Cholesterol biosynthesis	2	13.6×	0.267	SREBF1, SREBF2
Bicarbonate transporters	2	13.6×	0.267	SLC4A8, SLC4A10
Formation of the posterior neural plate	2	13.6×	0.267	TBX6, ZEB2
Regulation of commissural axon pathfinding by SLIT and ROBO	2	11.3×	0.267	ROBO1, ROBO2
Deadenylation-dependent mRNA decay	2	10.5×	0.267	SKIC2, LSM2
Glucose metabolism	2	10.5×	0.267	ALDOA, SEC13
Myogenesis	3	6.8×	0.267	CTNNA1, TCF4, SPAG9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 228 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 cytokine production	9	9.8×	5e-04	BTN1A1, BTN2A1, BTN2A2, BTN3A1, BTN3A2, BTN3A3, BTNL2, TRAF3 (+1 more)
learning	8	9.8×	1e-03	DRD3, NRXN1, ATXN1, TH, CNTNAP2, NLGN4X, SHANK2, PAK6
social behavior	8	9.5×	1e-03	DRD3, MECP2, NRXN1, ATXN1, TBX1, CNTNAP2, NLGN4X, SHANK2
prepulse inhibition	4	19.7×	0.016	DRD2, DRD3, SLC6A3, CNTNAP2
urate transport	3	31.7×	0.022	SLC17A1, SLC17A3, SLC2A9
hyaloid vascular plexus regression	3	31.7×	0.022	DRD2, SLC6A3, TH
vocalization behavior	4	15.6×	0.025	NRXN1, CNTNAP2, NLGN4X, SHANK2
T cell receptor signaling pathway	8	5.3×	0.026	BTN1A1, BTN2A1, BTN2A2, BTN3A1, BTN3A2, BTN3A3, BTNL2, BTN2A3P
phosphate ion transport	3	24.6×	0.031	SLC17A1, SLC17A3, SLC34A1
sodium-dependent phosphate transport	3	24.6×	0.031	SLC17A1, SLC17A4, SLC34A1
locomotory behavior	7	5.5×	0.041	DRD2, DRD3, RELN, SLC18A2, SLC6A3, TH, PAK6
nervous system process involved in regulation of systemic arterial blood pressure	2	49.3×	0.045	DRD2, MECP2
acid secretion	2	49.3×	0.045	DRD2, DRD3
negative regulation of negative chemotaxis	2	49.3×	0.045	ROBO1, ROBO2
melanocyte migration	2	49.3×	0.045	KIT, ZEB2
membrane depolarization during atrial cardiac muscle cell action potential	2	49.3×	0.045	CACNA1C, CACNB2
urate metabolic process	3	20.2×	0.045	SLC17A1, SLC17A3, SLC2A9
sodium ion import across plasma membrane	4	10.9×	0.045	SLC12A2, SCNN1B, SLC34A1, SLC9A3
response to cocaine	4	10.2×	0.045	DRD2, DRD3, ST8SIA2, SLC6A3
positive regulation of axonogenesis	4	10.2×	0.045	ROBO1, ROBO2, SHOX2, ZEB2
synapse assembly	6	6.1×	0.045	DRD2, MECP2, NRXN1, NLGN4X, SHANK2, GPHN
visual learning	5	6.7×	0.063	DRD2, DRD3, KIT, MECP2, ATXN1
response to histamine	2	37.0×	0.069	DRD2, DRD3
hematopoietic stem cell migration	2	37.0×	0.069	KIT, BCL11B
cellular response to metal ion	2	37.0×	0.069	SLC34A1, TLR9
cognition	5	6.3×	0.074	SLC6A3, TH, TNF, CYFIP1, CHRFAM7A
synapse organization	5	6.2×	0.077	SYN2, GET1, PRRT1, NLGN4X, SHANK2
adult behavior	4	8.2×	0.077	NRXN1, CNTNAP2, NLGN4X, SHANK2
regulation of DNA repair	5	6.1×	0.077	ATXN7, BABAM2, TAF5, TAF9, ACTR5
adenylate cyclase-inhibiting dopamine receptor signaling pathway	2	29.6×	0.079	DRD2, DRD3

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 10 · Undrugged: 29

Druggability breadth: 92 of 250 evidence-associated genes (37%) 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
SLC12A2	BUMETANIDE
CACNA1C	REMIFENTANIL
DRD2	CABERGOLINE
DRD3	CABERGOLINE
KIT	PONATINIB
SLC18A2	TETRABENAZINE
TBXA2R	CANDESARTAN CILEXETIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DRD3	448	4
DRD2	298	4
TBXA2R	210	4
KIT	99	4
CACNA1C	85	4
SLC18A2	6	4
SLC12A2	1	4
ALDOA	1	2
TAF9	1	2
UTRN	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BUMETANIDE	4	SLC12A2
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C, DRD2, DRD3
CLOTRIMAZOLE	4	CACNA1C, DRD2, DRD3, TBXA2R
PROPIVERINE	4	CACNA1C, DRD3
DIBUCAINE	4	CACNA1C
IMIPRAMINE	4	CACNA1C, DRD2, DRD3
DULOXETINE	4	CACNA1C, DRD2, DRD3
QUINIDINE	4	CACNA1C, DRD2, DRD3
ESTRADIOL	4	CACNA1C
TOLTERODINE	4	CACNA1C
PIMOZIDE	4	CACNA1C, DRD2, DRD3, TBXA2R
NIMODIPINE	4	CACNA1C
NICARDIPINE	4	CACNA1C, DRD3, TBXA2R
AMLODIPINE	4	CACNA1C, DRD2, DRD3, TBXA2R
VARDENAFIL	4	CACNA1C
CLEMASTINE	4	CACNA1C, DRD2, DRD3
ISRADIPINE	4	CACNA1C, TBXA2R
TERFENADINE	4	CACNA1C, DRD2, DRD3, TBXA2R
NISOLDIPINE	4	CACNA1C, DRD3
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C
NIFEDIPINE	4	CACNA1C
XANOMELINE	4	CACNA1C, DRD3
DILTIAZEM	4	CACNA1C
PRENYLAMINE	4	CACNA1C, DRD2, DRD3
OLICERIDINE	4	CACNA1C, DRD2, DRD3
PROPRANOLOL	4	CACNA1C, DRD3
ALVIMOPAN	4	CACNA1C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
DRD2	2,636	Binding:2064, Functional:517, ADMET:54, Unclassified:1
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
DRD3	1,359	Binding:1088, Functional:262, ADMET:6, Unclassified:3
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
TBXA2R	307	Binding:199, Functional:107, ADMET:1
SLC18A2	28	Binding:26, ADMET:1, Functional:1
CBX8	15	Binding:14, Functional:1
SLC12A2	13	Binding:9, Functional:4
ALDOA	9	Binding:9
CHI3L1	7	Binding:7
TAF9	6	Binding:6
UTRN	5	Binding:3, ADMET:2
CTNNA1	2	Binding:2
MECP2	1	Binding:1
SMARCA1	1	Binding:1
ARFGEF1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ZDHHC5	2.3.1.225	protein S-acyltransferase
ALDOA	4.1.2.13	fructose-bisphosphate aldolase
KIT	2.7.10.1	receptor protein-tyrosine kinase
ST8SIA2	2.4.99.8	alpha-N-acetylneuraminate alpha-2,8-sialyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CACNA1C	575
DRD2	2,636
DRD3	1,359
KIT	2,305
TBXA2R	307

Pharmacogenomics

Cohort genes with a PharmGKB record: 39; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

29 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)
BUMETANIDE	4	SLC12A2
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C, DRD2, DRD3
CLOTRIMAZOLE	4	CACNA1C, DRD2, DRD3, TBXA2R
PROPIVERINE	4	CACNA1C, DRD3
DIBUCAINE	4	CACNA1C
IMIPRAMINE	4	CACNA1C, DRD2, DRD3
DULOXETINE	4	CACNA1C, DRD2, DRD3
QUINIDINE	4	CACNA1C, DRD2, DRD3
ESTRADIOL	4	CACNA1C
TOLTERODINE	4	CACNA1C
PIMOZIDE	4	CACNA1C, DRD2, DRD3, TBXA2R
NIMODIPINE	4	CACNA1C
NICARDIPINE	4	CACNA1C, DRD3, TBXA2R
AMLODIPINE	4	CACNA1C, DRD2, DRD3, TBXA2R
VARDENAFIL	4	CACNA1C
CLEMASTINE	4	CACNA1C, DRD2, DRD3
ISRADIPINE	4	CACNA1C, TBXA2R
TERFENADINE	4	CACNA1C, DRD2, DRD3, TBXA2R
NISOLDIPINE	4	CACNA1C, DRD3
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C
NIFEDIPINE	4	CACNA1C
DILTIAZEM	4	CACNA1C
PRENYLAMINE	4	CACNA1C, DRD2, DRD3
OLICERIDINE	4	CACNA1C, DRD2, DRD3
PROPRANOLOL	4	CACNA1C, DRD3
ALVIMOPAN	4	CACNA1C

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	SLC12A2, CACNA1C, DRD2, DRD3, KIT, SLC18A2, TBXA2R
B	Phased (≥1) drug, not yet approved	3	ALDOA, TAF9, UTRN
C	Druggable family + PDB, no drug	1	CSMD1
D	Druggable family + AlphaFold only, no drug	4	ABCA13, ZDHHC5, ST8SIA2, ZP4
E	Difficult family or no structure, no drug	24	SYNGR1, CHI3L1, ZNF804A, CTNNA1, ZDBF2, DNAH9, LRP1, MECP2, NRXN1, RELN (+14 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ZNF804A	0	CACNA1C
SYNGR1	0	—
CSMD1	0	—
ABCA13	0	—
ZDHHC5	0	—
CHI3L1	7	—
CTNNA1	2	—
ZDBF2	0	—
DNAH9	0	—
LRP1	0	—
MECP2	1	—
NRXN1	0	—
RELN	0	—
SELENBP1	0	—
SHOX2	0	—
ST8SIA2	0	—
SLC4A8	0	—
SMARCA1	1	—
GET1	0	—
ZNF229	0	—
FAXDC2	0	—
RELT	0	—
SPAG9	0	—
ARHGEF15	0	—
PAQR8	0	—
ANAPC5	0	—
ZP4	0	—
ARFGEF1	1	—
CBX8	15	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,957.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	419
PHASE3	387
PHASE2	221
PHASE2/PHASE3	42
PHASE1/PHASE2	31

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02639702	PHASE4	RECRUITING	Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia
NCT03495024	PHASE4	RECRUITING	Smoking Cessation With Varenicline in Schizophrenia: Antipsychotic-Induced Neurological Symptoms as Correlates
NCT03575000	PHASE4	NOT_YET_RECRUITING	Bromocriptine for Patients With Schizophrenia and Prediabetes
NCT04580134	PHASE4	RECRUITING	CLOZAPINE Response in Biotype-1
NCT04892199	PHASE4	ACTIVE_NOT_RECRUITING	Does GLP-1RA Prevent Deterioration of Metabolic State in Prediabetic and Diabetic Patients Treated With Antipsychotic Medication?
NCT05208190	PHASE4	RECRUITING	Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial
NCT05316883	PHASE4	RECRUITING	Biomarkers in Clozapine-responding Schizophrenia
NCT05648591	PHASE4	RECRUITING	Safety and Tolerability of Open-Labeled Iloperidone in Adolescents
NCT05823532	PHASE4	RECRUITING	Anti-Inflammatory Challenge in Schizophrenia
NCT06174116	PHASE4	RECRUITING	Metabolic Effects of Adjunctive Lumateperone Treatment in Clozapine-Treated Patients With Schizophrenia
NCT06562608	PHASE4	RECRUITING	Anticholinergic Deprescription in Schizophrenia
NCT06923891	PHASE4	NOT_YET_RECRUITING	An Open-Label Study to Evaluate the Efficacy and Tolerability of Xanomeline/Trospium In First Episode/Early Phase Schizophrenia Patients
NCT07075237	PHASE4	NOT_YET_RECRUITING	Efficacy and Functional Recovery After Switching From Paliperidone Palmitate Injection to Oral Antipsychotics in Schizophrenia
NCT07105111	PHASE4	RECRUITING	A Study to Evaluate the Effectiveness of Valbenazine in Adult Participants With Tardive Dyskinesia (TD) Who Remain Symptomatic While Receiving or After Stopping a Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor
NCT07153835	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Paliperidone in Schizophrenia - Bangladesh Study
NCT07221877	PHASE4	RECRUITING	A Study to Evaluate the Effect of KarXT on Urological Safety
NCT07615075	PHASE4	NOT_YET_RECRUITING	Clinical Trial of an IL-23 Inhibitor for Immune Activation in Clinical Trial of an IL-23 Inhibitor for Immune Activation in People With Schizophrenia
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ZIPRASIDONE	4	138
OLANZAPINE	4	120
RISPERIDONE	4	65
QUETIAPINE	4	61
PALIPERIDONE PALMITATE	4	59
ARIPIPRAZOLE	4	48
CARIPRAZINE	4	42
LURASIDONE	4	33
CLOZAPINE	4	28
HALOPERIDOL	4	24
PALIPERIDONE	4	22
AMISULPRIDE	4	18
BUPROPION	4	18
VARENICLINE	4	18
ASENAPINE	4	16
BREXPIPRAZOLE	4	16
CITALOPRAM	4	15
ATOMOXETINE	4	13
SERTINDOLE	4	10
XANOMELINE	4	10
ILOPERIDONE	4	9
PERPHENAZINE	4	9
TROSPIUM CHLORIDE	4	9
ESCITALOPRAM	4	8
GALANTAMINE	4	8
LUMATEPERONE	4	8
MEMANTINE	4	8
MINOCYCLINE	4	8
ARIPIPRAZOLE LAUROXIL	4	7
CYCLOSERINE	4	7