Obsessive-compulsive disorder

Summary

Obsessive-compulsive disorder (MONDO:0008114) is a disease with 75 cohort genes (307 GWAS associations across 83 studies) and 618 clinical trials. Top therapeutic interventions include fluvoxamine, fluoxetine, and cycloserine.

At a glance

• Cohort genes: 75
• GWAS associations: 307
• ClinVar variants: 2
• Clinical trials: 618

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	obsessive-compulsive disorder
Mondo ID	MONDO:0008114
EFO	EFO:0004242
MeSH	D009771
OMIM	164230
DOID	DOID:10933
ICD-10-CM	F42
ICD-11	1582741816
NCIT	C88411
SNOMED CT	191736004
UMLS	C0028768
MedGen	14445
Is cancer (heuristic)	no

Also known as: obsessive compulsive disorder · obsessive-compulsive disorder · obsessive-compulsive disorder, susceptibility to · OCD

Data availability: 2 ClinVar variants · 307 GWAS associations (83 studies) · 1 GenCC gene-disease record · 6 cell lines.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › anxiety disorder › obsessive-compulsive disorder

Related subtypes (9): separation anxiety disorder, neurocirculatory asthenia, generalized anxiety disorder, phobic disorder, acute stress disorder, neurotic disorder, panic disorder, anxiety, mixed anxiety and depressive disorder

Genetics & variants

GWAS landscape

307 GWAS associations across 83 studies. Top hits map to 33 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2799079	2e-31	ZSCAN26	?
rs9379897	1e-28	ABT1 - ZNF322	?
rs13217619	1e-27	ZSCAN31	?
rs10465868	2e-20	LINC01360 - LINC02238	?
rs4298967	8e-20	CACNA1C, CACNA1C-IT3	?
rs9834970	2e-17	HSPD1P6 - LINC02033	?
rs7822799	2e-17	TSNARE1	?
rs12129573	5e-17	RN7SKP19 - LINC01360	?
rs4481150	5e-17	ITIH3	?
rs644883	7e-17	OR5BA1P - OR5AZ1P	?
rs12658451	2e-16	NIHCOLE - RNU6-334P	?
rs1702294	3e-16	MIR137HG	?
rs7085104	3e-16	BORCS7-ASMT	?
rs7531118	1e-15	LINC02796	?
rs4129585	2e-15	TSNARE1	?
rs4788196	3e-15	TMEM219	?
rs61867293	8e-15	SORCS3	?
rs11688767	2e-14	EIF2S2P7 - ACTG1P22	?
rs10883832	3e-14	NT5C2	?
rs71395455	5e-14	ZSCAN2-AS1, ZSCAN2	?
rs5758265	5e-14	L3MBTL2-AS1, L3MBTL2	?
rs3001723	7e-14	PTPRF	?
rs12668848	1e-13	MAD1L1	?
rs2582897	3e-13	METTL15 - LINC02758	?
rs10149470	5e-13	RNU7-160P - BAG5	?
rs11693528	1e-12	FTCDNL1 - RN7SL717P	?
rs12958048	1e-12	TCF4	?
rs7405404	1e-12	TMF1P1 - ERCC4	?
rs140505938	2e-12	RPL6P31 - VPS45	?
rs1950829	2e-12	LRFN5	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90016615	Peyrot WJ	2021	170,756	2,688	Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST90016623	Peyrot WJ	2021	40,675	2,688	Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST90624485	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624490	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624494	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624497	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624500	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.
GCST90624504	Ding H	2022	32,858	0	Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.
GCST90624507	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	2
Tier 3: regulatory	2
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	49
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	39
intergenic_variant	7
regulatory_region_variant	2
5_prime_UTR_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2799079	6	28267398	A>C	0.05	5_prime_UTR_variant	ZSCAN26	2e-31	Tier 2: splice/UTR
rs9379897	6	26601298	T>C	0.05	intergenic_variant	ABT1 - ZNF322	1e-28	Tier 4: intronic/intergenic
rs13217619	6	28338894	T>C	0.05	intron_variant	ZSCAN31	1e-27	Tier 4: intronic/intergenic
rs10465868	1	73414971	A>C,G	0.05	intron_variant	LINC01360 - LINC02238	2e-20	Tier 4: intronic/intergenic
rs4298967	12	2299028	A>C,G,T	0.05	intron_variant	CACNA1C, CACNA1C-IT3	8e-20	Tier 4: intronic/intergenic
rs9834970	3	36814539	T>C	0.05	regulatory_region_variant	HSPD1P6 - LINC02033	2e-17	Tier 3: regulatory
rs7822799	8	142242486	A>C,G,T	0.05	intron_variant	TSNARE1	2e-17	Tier 4: intronic/intergenic
rs12129573	1	73302683	C>A	0.05	intron_variant	RN7SKP19 - LINC01360	5e-17	Tier 4: intronic/intergenic
rs4481150	3	52803777	T>C,G	0.05	intron_variant	ITIH3	5e-17	Tier 4: intronic/intergenic
rs644883	11	57896050	C>G	0.05	intergenic_variant	OR5BA1P - OR5AZ1P	7e-17	Tier 4: intronic/intergenic
rs12658451	5	104568336	T>C	0.05	intron_variant	NIHCOLE - RNU6-334P	2e-16	Tier 4: intronic/intergenic
rs1702294	1	98036428	T>A,C,G	0.05	intron_variant	MIR137HG	3e-16	Tier 4: intronic/intergenic
rs7085104	10	102869116	A>G	0.05	intron_variant	BORCS7-ASMT	3e-16	Tier 4: intronic/intergenic
rs7531118	1	72371556	T>C	0.05	intron_variant	LINC02796	1e-15	Tier 4: intronic/intergenic
rs4129585	8	142231572	A>C,G,T	0.05	intron_variant	TSNARE1	2e-15	Tier 4: intronic/intergenic
rs4788196	16	29956113	A>C,G	0.05	intron_variant	TMEM219	3e-15	Tier 4: intronic/intergenic
rs61867293	10	104804166	C>T	0.05	intron_variant	SORCS3	8e-15	Tier 4: intronic/intergenic
rs11688767	2	57761059	A>G,T	0.05	intron_variant	EIF2S2P7 - ACTG1P22	2e-14	Tier 4: intronic/intergenic
rs10883832	10	103111522	T>A,G	0.05	intron_variant	NT5C2	3e-14	Tier 4: intronic/intergenic
rs71395455	15	84610573	A>C,G,T	0.05	intron_variant	ZSCAN2-AS1, ZSCAN2	5e-14	Tier 4: intronic/intergenic
rs5758265	22	41221893	G>A,C,T	0.05	intron_variant	L3MBTL2-AS1, L3MBTL2	5e-14	Tier 4: intronic/intergenic
rs3001723	1	43572014	G>A	0.05	intron_variant	PTPRF	7e-14	Tier 4: intronic/intergenic
rs12668848	7	1981360	G>A,T	0.05	intron_variant	MAD1L1	1e-13	Tier 4: intronic/intergenic
rs2582897	11	28594153	T>A,C	0.05	intergenic_variant	METTL15 - LINC02758	3e-13	Tier 4: intronic/intergenic
rs10149470	14	103551616	A>G,T	0.05	regulatory_region_variant	RNU7-160P - BAG5	5e-13	Tier 3: regulatory
rs11693528	2	199871784	C>G,T	0.05	intron_variant	FTCDNL1 - RN7SL717P	1e-12	Tier 4: intronic/intergenic
rs12958048	18	55434367	A>G,T	0.05	intron_variant	TCF4	1e-12	Tier 4: intronic/intergenic
rs7405404	16	13656002	T>A,C,G	0.05	intron_variant	TMF1P1 - ERCC4	1e-12	Tier 4: intronic/intergenic
rs140505938	1	150059494	C>T	0.05	intron_variant	RPL6P31 - VPS45	2e-12	Tier 4: intronic/intergenic
rs1950829	14	41628734	A>G	0.05	intron_variant	LRFN5	2e-12	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1300132	NM_001045.6(SLC6A4):c.1745dup (p.Thr583fs)	SLC6A4	Likely pathogenic	criteria provided, single submitter
1031015	NM_001045.6(SLC6A4):c.837+2T>C	SLC6A4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 54 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
SLC6A4	Limited	Autosomal dominant	obsessive-compulsive disorder	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
CNNM4	Orphanet:1873	Jalili syndrome
ATXN7	Orphanet:94147	Spinocerebellar ataxia type 7
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
SOX5	Orphanet:313884	12p12.1 microdeletion syndrome
SOX5	Orphanet:313892	Developmental and speech delay due to SOX5 deficiency
SOX5	Orphanet:626	Large/giant congenital melanocytic nevus
TCF20	Orphanet:528084	Non-specific syndromic intellectual disability
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
TFAP2B	Orphanet:46627	Char syndrome
TFAP2B	Orphanet:466729	Familial patent arterial duct
BCL11B	Orphanet:662829	Intellectual disability-speech delay-dysmorphic features-T cell abnormalities syndrome
SLC30A9	Orphanet:505242	Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome
KDM3B	Orphanet:633004	KDM3B-related intellectual disability-facial dysmorphism-short stature syndrome
PCLO	Orphanet:97249	Pontocerebellar hypoplasia type 3
ATP9A	Orphanet:528084	Non-specific syndromic intellectual disability
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
CACNA1I	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
CACNB2	Orphanet:130	Brugada syndrome
VPS45	Orphanet:369852	Congenital neutropenia-myelofibrosis-nephromegaly syndrome
TRIM8	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
KIZ	Orphanet:791	Retinitis pigmentosa
SALL4	Orphanet:2307	IVIC syndrome
SALL4	Orphanet:233	Duane retraction syndrome
SALL4	Orphanet:261638	Okihiro syndrome due to 20q13 microdeletion
SALL4	Orphanet:261647	Okihiro syndrome due to a point mutation
SALL4	Orphanet:959	Acro-renal-ocular syndrome
CD320	Orphanet:280183	Methylmalonic aciduria due to transcobalamin receptor defect
SYNE2	Orphanet:98853	Autosomal dominant Emery-Dreifuss muscular dystrophy
DHX38	Orphanet:791	Retinitis pigmentosa
RIMS1	Orphanet:1872	Cone rod dystrophy
PMFBP1	Orphanet:529970	Male infertility due to acephalic spermatozoa

Cohort genes → proteins

75 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	74
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC6A4	HGNC:11050	ENSG00000108576	P31645	Sodium-dependent serotonin transporter	gencc,clinvar
RGS6	HGNC:10002	ENSG00000182732	P49758	Regulator of G-protein signaling 6	gwas
RNU6-1	HGNC:10227	ENSG00000206625		RNA, U6 small nuclear 1	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
RTN1	HGNC:10467	ENSG00000139970	Q16799	Reticulon-1	gwas
CNNM4	HGNC:105	ENSG00000158158	Q6P4Q7	Metal transporter CNNM4	gwas
ATXN7	HGNC:10560	ENSG00000163635	O15265	Ataxin-7	gwas
SHMT2	HGNC:10852	ENSG00000182199	P34897	Serine hydroxymethyltransferase, mitochondrial	gwas
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	gwas
SOX5	HGNC:11201	ENSG00000134532	P35711	Transcription factor SOX-5	gwas
BTF3P11	HGNC:1126	ENSG00000118903		basic transcription factor 3 pseudogene 11	gwas
SRPK2	HGNC:11306	ENSG00000135250	P78362	SRSF protein kinase 2	gwas
TCF20	HGNC:11631	ENSG00000100207	Q9UGU0	Transcription factor 20	gwas
TCF4	HGNC:11634	ENSG00000196628	P15884	Transcription factor 4	gwas
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	gwas
TFAP2B	HGNC:11743	ENSG00000008196	Q92481	Transcription factor AP-2-beta	gwas
TRPC4	HGNC:12336	ENSG00000133107	Q9UBN4	Short transient receptor potential channel 4	gwas
TXNL1	HGNC:12436	ENSG00000091164	O43396	Thioredoxin-like protein 1	gwas
BCL11B	HGNC:13222	ENSG00000127152	Q9C0K0	B-cell lymphoma/leukemia 11B	gwas
SLC30A9	HGNC:1329	ENSG00000014824	Q6PML9	Proton-coupled zinc antiporter SLC30A9, mitochondrial	gwas
FAM53C	HGNC:1336	ENSG00000120709	Q9NYF3	Protein FAM53C	gwas
KDM3B	HGNC:1337	ENSG00000120733	Q7LBC6	Lysine-specific demethylase 3B	gwas
PCLO	HGNC:13406	ENSG00000186472	Q9Y6V0	Protein piccolo	gwas
WDR7	HGNC:13490	ENSG00000091157	Q9Y4E6	WD repeat-containing protein 7	gwas
ATP9A	HGNC:13540	ENSG00000054793	O75110	Probable phospholipid-transporting ATPase IIA	gwas
FBXL3	HGNC:13599	ENSG00000005812	Q9UKT7	F-box/LRR-repeat protein 3	gwas
FOLH1B	HGNC:13636	ENSG00000134612	Q9HBA9	Putative N-acetylated-alpha-linked acidic dipeptidase	gwas
ZKSCAN3	HGNC:13853	ENSG00000189298	Q9BRR0	Zinc finger protein with KRAB and SCAN domains 3	gwas
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	gwas
CACNA1I	HGNC:1396	ENSG00000100346	Q9P0X4	Voltage-dependent T-type calcium channel subunit alpha-1I	gwas
CACNB2	HGNC:1402	ENSG00000165995	Q08289	Voltage-dependent L-type calcium channel subunit beta-2	gwas
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
ZSCAN31	HGNC:14097	ENSG00000235109	Q96LW9	Zinc finger and SCAN domain-containing protein 31	gwas
PMEPA1	HGNC:14107	ENSG00000124225	Q969W9	Protein TMEPAI	gwas
PCDH18	HGNC:14268	ENSG00000189184	Q9HCL0	Protocadherin-18	gwas
IFT81	HGNC:14313	ENSG00000122970	Q8WYA0	Intraflagellar transport protein 81 homolog	gwas
MRPL33	HGNC:14487	ENSG00000243147	O75394	Large ribosomal subunit protein bL33m	gwas
VPS45	HGNC:14579	ENSG00000136631	Q9NRW7	Vacuolar protein sorting-associated protein 45	gwas
IMMP2L	HGNC:14598	ENSG00000184903	Q96T52	Mitochondrial inner membrane protease subunit 2	gwas
LETM2	HGNC:14648	ENSG00000165046	Q2VYF4	LETM1 domain-containing protein LETM2, mitochondrial	gwas
ACTR5	HGNC:14671	ENSG00000101442	Q9H9F9	Actin-related protein 5	gwas
KCTD12	HGNC:14678	ENSG00000178695	Q96CX2	BTB/POZ domain-containing protein KCTD12	gwas
PPP1R13B	HGNC:14950	ENSG00000088808	Q96KQ4	Apoptosis-stimulating of p53 protein 1	gwas
SNAP91	HGNC:14986	ENSG00000065609	O60641	Clathrin coat assembly protein AP180	gwas
CACNA2D3	HGNC:15460	ENSG00000157445	Q8IZS8	Voltage-dependent calcium channel subunit alpha-2/delta-3	gwas
TRIM8	HGNC:15579	ENSG00000171206	Q9BZR9	E3 ubiquitin-protein ligase TRIM8	gwas
TFAP2D	HGNC:15581	ENSG00000008197	Q7Z6R9	Transcription factor AP-2-delta	gwas
PPP1R16B	HGNC:15850	ENSG00000101445	Q96T49	Protein phosphatase 1 regulatory inhibitor subunit 16B	gwas
KIZ	HGNC:15865	ENSG00000088970	Q2M2Z5	Centrosomal protein kizuna	gwas
SALL4	HGNC:15924	ENSG00000101115	Q9UJQ4	Sal-like protein 4	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
RGS6	Regulator of G-protein signaling 6	Regulates G protein-coupled receptor signaling cascades.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
RTN1	Reticulon-1	Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.
CNNM4	Metal transporter CNNM4	Probable metal transporter.
ATXN7	Ataxin-7	Acts as a component of the SAGA (aka STAGA) transcription coactivator-HAT complex.
SHMT2	Serine hydroxymethyltransferase, mitochondrial	Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
SOX5	Transcription factor SOX-5	Transcription factor involved in chondrocytes differentiation and cartilage formation.
SRPK2	SRSF protein kinase 2	Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splici…
TCF20	Transcription factor 20	Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression.
TCF4	Transcription factor 4	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
ELP4	Elongator complex protein 4	Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).
TFAP2B	Transcription factor AP-2-beta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
TRPC4	Short transient receptor potential channel 4	Forms a receptor-activated non-selective calcium permeant cation channel.
TXNL1	Thioredoxin-like protein 1	Active thioredoxin with a redox potential of about -250 mV.
BCL11B	B-cell lymphoma/leukemia 11B	Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals.
SLC30A9	Proton-coupled zinc antiporter SLC30A9, mitochondrial	Mitochondrial proton-coupled zinc ion antiporter mediating the export of zinc from the mitochondria and involved in zinc homeostasis, zinc mobilization as well as mitochondrial morphology and health.
KDM3B	Lysine-specific demethylase 3B	Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code.
PCLO	Protein piccolo	Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released.
ATP9A	Probable phospholipid-transporting ATPase IIA	Plays a role in regulating membrane trafficking of cargo proteins, namely endosome to plasma membrane recycling, probably acting through RAB5 and RAB11 activation.
FBXL3	F-box/LRR-repeat protein 3	Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function.
FOLH1B	Putative N-acetylated-alpha-linked acidic dipeptidase	Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity.
ZKSCAN3	Zinc finger protein with KRAB and SCAN domains 3	Transcriptional factor that binds to the consensus sequence 5’-[GT][AG][AGT]GGGG-3’ and acts as a repressor of autophagy.
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.
CACNA1I	Voltage-dependent T-type calcium channel subunit alpha-1I	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
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.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
ZSCAN31	Zinc finger and SCAN domain-containing protein 31	May function as a transcription factor.
PMEPA1	Protein TMEPAI	Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression.
PCDH18	Protocadherin-18	Potential calcium-dependent cell-adhesion protein.
IFT81	Intraflagellar transport protein 81 homolog	Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.
VPS45	Vacuolar protein sorting-associated protein 45	May play a role in vesicle-mediated protein trafficking from the Golgi stack through the trans-Golgi network.
IMMP2L	Mitochondrial inner membrane protease subunit 2	Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space.
ACTR5	Actin-related protein 5	Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
KCTD12	BTB/POZ domain-containing protein KCTD12	Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response.
PPP1R13B	Apoptosis-stimulating of p53 protein 1	Regulator that plays a central role in regulation of apoptosis via its interaction with p53/TP53.
SNAP91	Clathrin coat assembly protein AP180	Adaptins are components of the adapter complexes which link clathrin to receptors in coated vesicles.
CACNA2D3	Voltage-dependent calcium channel subunit alpha-2/delta-3	The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
TRIM8	E3 ubiquitin-protein ligase TRIM8	E3 ubiquitin-protein ligase that participates in multiple biological processes including cell survival, differentiation, apoptosis, and in particular, the innate immune response.
TFAP2D	Transcription factor AP-2-delta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
PPP1R16B	Protein phosphatase 1 regulatory inhibitor subunit 16B	Regulator of protein phosphatase 1 (PP1) that acts as a positive regulator of pulmonary endothelial cell (EC) barrier function.
KIZ	Centrosomal protein kizuna	Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation.
SALL4	Sal-like protein 4	Transcription factor with a key role in the maintenance and self-renewal of embryonic and hematopoietic stem cells.
OSBPL3	Oxysterol-binding protein-related protein 3	Lipid transfer protein that mediates the non-vesicular transport of phosphoinositide 4-phosphate (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate), or PI(4)P) at the plasma membrane (PM)/ endoplasmic reticulum (ER) contact sit…
OTUD7B	OTU domain-containing protein 7B	Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses.
CD320	CD320 antigen	Receptor for transcobalamin saturated with cobalamin (TCbl).
SORCS3	VPS10 domain-containing receptor SorCS3	Plays an important role in modulating synaptic transmission and plasticity in the hippocampus, probably by affecting the trafficking and localization ofAMPA-type glutamate receptors in the postsynaptic density.
POSTN	Periostin	Induces cell attachment and spreading and plays a role in cell adhesion.
FAIM2	Protein lifeguard 2	Antiapoptotic protein which protects cells uniquely from Fas-induced apoptosis.

Protein-family classification

Druggable: 18 · Difficult: 20 · Unknown: 37 · Druggable fraction: 0.24

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	3	4.5×	0.168
Transcription factor	15	1.6×	0.168
Complement	1	3.6×	0.639
Antibody/Immunoglobulin	4	1.6×	0.639
Scaffold/PPI	5	1.1×	0.777
Kinase	3	1.1×	0.777
Transporter	1	1.0×	0.777
Protease	2	1.0×	0.777
Other/Unknown	37	0.9×	0.894
Enzyme (other)	4	0.6×	0.894

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC6A4	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_serotonin_N, SNS_sf
RGS6	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS
RNU6-1	Other/Unknown	no
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
RTN1	Other/Unknown	no		Reticulon, RTN1-4
CNNM4	Enzyme (other)	yes	7.2.2.14	cNMP-bd_dom, CBS_dom, CNNM
ATXN7	Other/Unknown	no		SCA7_dom, Ataxin-7-like_regulator
SHMT2	Enzyme (other)	yes	2.1.2.1	Ser_HO-MeTrfase, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
SOX5	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
BTF3P11	Other/Unknown	no
SRPK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TCF20	Transcription factor	no		Znf_PHD, Znf_RING/FYVE/PHD, EPHD
TCF4	Transcription factor	no	7.6.2.3	bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
TFAP2B	Transcription factor	no		TF_AP2, TF_AP2_beta, TF_AP2_C
TRPC4	Ion channel	yes		Ankyrin_rpt, TRPC_channel, TRPC4_channel
TXNL1	Other/Unknown	no		Galactose-bd-like_sf, PITH_dom, Thioredoxin_domain
BCL11B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF
SLC30A9	Other/Unknown	no		Cation_efflux, DNA-bd_dom_put_sf, Cation_efflux_TMD_sf
FAM53C	Other/Unknown	no		FAM53
KDM3B	Enzyme (other)	yes	1.14.11.65	JmjC_dom, LSDs-like, KDM3A/B_DUF7030
PCLO	Transcription factor	no		C2_dom, PDZ, Znf_piccolo
WDR7	Scaffold/PPI	no		WD40_rpt, Quinoprotein_ADH-like_sf, WD40/YVTN_repeat-like_dom_sf
ATP9A	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
FBXL3	Other/Unknown	no		F-box_dom, LRR_dom_sf, F-box-like_dom_sf
FOLH1B	Protease	yes		TFR-like_dimer_dom, Peptidase_M28, TFR-like_dimer_dom_sf
ZKSCAN3	Transcription factor	no		KRAB, SCAN_dom, Znf_C2H2_type
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CACNA1I	Ion channel	yes		VDCCAlpha1, VDCC_T_a1, Ion_trans_dom
CACNB2	Scaffold/PPI	no		VDCC_L_bsu, SH3_domain, VDCC_L_b2su
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
ZSCAN31	Transcription factor	no		SCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
PMEPA1	Other/Unknown	no		TMEPAI/LRAD4
PCDH18	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Cadherin-like_sf
IFT81	Other/Unknown	no		IFT81, IFT81_CH, IFT81_N_sf
MRPL33	Other/Unknown	no		Ribosomal_bL33, Ribosomal_zn-bd, Ribosomal_bL33_sf
VPS45	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
IMMP2L	Protease	yes		Pept_S26A_signal_pept_1, Peptidase_S26, Pept_S26A_signal_pept_1_CS
LETM2	Other/Unknown	no		LETM1-like_RBD, LETM1/MDM38-like, LETM2_N
ACTR5	Other/Unknown	no		Actin, Actin_CS, ATPase_NBD
KCTD12	Other/Unknown	no		BTB/POZ_dom, T1-type_BTB, SKP1/BTB/POZ_sf
PPP1R13B	Scaffold/PPI	no		SH3_domain, Ankyrin_rpt, ASPP1_RA
SNAP91	Other/Unknown	no		ENTH_VHS, ANTH_dom, ENTH
CACNA2D3	Other/Unknown	no		VWF_A, VWA_N, VDCC_a2/dsu
TRIM8	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
TFAP2D	Transcription factor	no		TF_AP2, TF_AP2_C
PPP1R16B	Scaffold/PPI	no		Ankyrin_rpt, Pase-1_reg_su_16AB, Ankyrin_rpt-contain_sf
KIZ	Other/Unknown	no		Centrosomal_kizuma
SALL4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger

Expression context

Cohort genes with no expression data: 0.

63 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	11
middle temporal gyrus	10
cortical plate	8
calcaneal tendon	8
endothelial cell	6
ventricular zone	6
sural nerve	5
left testis	5
right testis	5
oocyte	4
mucosa of transverse colon	4
buccal mucosa cell	4
male germ line stem cell (sensu Vertebrata) in testis	4
sperm	4
primordial germ cell in gonad	4
jejunal mucosa	3
adrenal tissue	3
right adrenal gland	3
secondary oocyte	3
male germ cell	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC6A4	162	tissue_specific	marker	right lung, jejunal mucosa, ileal mucosa
RGS6	185	broad	marker	cortical plate, sural nerve, middle temporal gyrus
RNU6-1	117	broad	yes	sural nerve, adrenal tissue, corpus callosum
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland
RTN1	270	broad	marker	Brodmann (1909) area 23, endothelial cell, pons
CNNM4	189	ubiquitous	marker	mucosa of transverse colon, rectum, ileal mucosa
ATXN7	290	ubiquitous	marker	mucosa of paranasal sinus, jejunal mucosa, superficial temporal artery
SHMT2	288	ubiquitous	marker	tendon of biceps brachii, cartilage tissue, right lobe of liver
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
SOX5	221	ubiquitous	marker	cortical plate, calcaneal tendon, synovial joint
BTF3P11	76		yes	male germ line stem cell (sensu Vertebrata) in testis, endometrium epithelium, Brodmann (1909) area 10
SRPK2	293	ubiquitous	marker	sperm, male germ cell, pons
TCF20	134	ubiquitous	yes	cortical plate, ganglionic eminence, tonsil
TCF4	292	ubiquitous	marker	endothelial cell, skin of hip, pericardium
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad
TFAP2B	128	broad	marker	corpus epididymis, cauda epididymis, oocyte
TRPC4	158	broad	yes	stromal cell of endometrium, decidua, smooth muscle tissue
TXNL1	296	ubiquitous	marker	parotid gland, cervix squamous epithelium, endothelial cell
BCL11B	211	broad	marker	thymus, upper leg skin, cortical plate
SLC30A9	300	ubiquitous	marker	cortical plate, calcaneal tendon, germinal epithelium of ovary
FAM53C	290	ubiquitous	marker	left testis, right testis, blood
KDM3B	296	ubiquitous	marker	ventricular zone, ganglionic eminence, gluteal muscle
PCLO	235	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, cerebellar vermis
WDR7	288	ubiquitous	yes	endothelial cell, middle temporal gyrus, Brodmann (1909) area 23
ATP9A	299	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 46, Brodmann (1909) area 23
FBXL3	254	ubiquitous	marker	cardiac muscle of right atrium, calcaneal tendon, upper arm skin
FOLH1B	52		marker	primordial germ cell in gonad, liver, right lobe of liver
ZKSCAN3	193	ubiquitous	yes	primordial germ cell in gonad, sperm, hair follicle
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
CACNA1I	145		yes	Brodmann (1909) area 23, primary visual cortex, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 21.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRAF	7,394
SHMT2	5,293
SRPK2	3,839
POSTN	3,600
DHX38	3,449
TCF4	3,342
CACNA1C	3,145
RBFOX1	2,990
MRPL33	2,743
L3MBTL2	2,633

Intra-cohort edges

A	B	Sources
AS3MT	CNNM2	string_interaction
AS3MT	ZSCAN31	string_interaction
ATP9A	MOB4	string_interaction
CACNA1C	CACNA1I	string_interaction
CACNA1C	CACNA2D3	string_interaction
CACNA1C	CACNB2	intact, string_interaction
CACNA1C	CSMD1	string_interaction
CACNA1C	PCDH18	intact
CACNA1I	CACNB2	string_interaction
CACNA2D3	CACNB2	string_interaction
CNNM2	RIMS1	intact
CSMD1	PCLO	string_interaction
FAIM2	NEGR1	string_interaction
FAIM2	TFAP2B	string_interaction
FAM53C	KDM3B	string_interaction
IMMP2L	SHMT2	biogrid_interaction
NEGR1	SORCS3	string_interaction
NEGR1	TFAP2B	string_interaction
RIMS1	RTN1	intact
RIMS1	SRPK2	intact
TFAP2B	TFAP2D	biogrid_interaction

Structural data

PDB: 42 · AlphaFold-only: 29 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRAF	P15056	131
MRPL33	O75394	86
MRPS33	Q9Y291	77
KDM3B	Q7LBC6	36
CACNA1C	Q13936	33
SLC6A4	P31645	30
TUBGCP5	Q96RT8	28
SHMT2	P34897	27
SALL4	Q9UJQ4	13
TXNL1	O43396	11
CNNM2	Q9H8M5	7
ACTR5	Q9H9F9	6
CD320	Q9NPF0	6
ATXN7	O15265	5
TCF4	P15884	5
ATP9A	O75110	4
CACNA1I	Q9P0X4	4
DHX38	Q92620	4
RBFOX1	Q9NWB1	4
SRPK2	P78362	3
TRPC4	Q9UBN4	3
CACNB2	Q08289	3
OSBPL3	Q9H4L5	3
OTUD7B	Q6GQQ9	3
POSTN	Q15063	3
SYNE2	Q8WXH0	3
L3MBTL2	Q969R5	3
CNNM4	Q6P4Q7	2
KCTD12	Q96CX2	2
MOB4	Q9Y3A3	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FOLH1B	Q9HBA9	96.69
VPS45	Q9NRW7	90.65
IMMP2L	Q96T52	87.66
ATPAF2	Q8N5M1	86.07
IFT81	Q8WYA0	83.45
OLFM4	Q6UX06	83.34
CACNA2D3	Q8IZS8	83.30
VSIG2	Q96IQ7	80.30
CDH10	Q9Y6N8	78.29
FAIM2	Q9BWQ8	77.90
PMFBP1	Q8TBY8	77.80
SORCS3	Q9UPU3	75.70
ELP4	Q96EB1	74.49
WDR7	Q9Y4E6	74.31
TRIM8	Q9BZR9	72.26
PPP1R16B	Q96T49	70.73
ZSCAN31	Q96LW9	67.96
SLC45A1	Q9Y2W3	66.26
LETM2	Q2VYF4	62.77
TFAP2D	Q7Z6R9	62.75
ZKSCAN3	Q9BRR0	60.16
SOX5	P35711	58.95
PMEPA1	Q969W9	57.03
SNAP91	O60641	55.46
KIZ	Q2M2Z5	54.82
FAM53C	Q9NYF3	52.63
BCL11B	Q9C0K0	51.76
RTN1	Q16799	48.88
TCF20	Q9UGU0	39.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 575. Enrichment computed across 229 evidence-associated genes (125 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 125 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MECP2 regulates transcription factors	2	36.5×	0.170	RBFOX1, MEF2C
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	3	15.2×	0.170	TFAP2B, TFAP2D, KIT
Synaptic adhesion-like molecules	3	13.1×	0.170	GRIN2A, PTPRD, PTPRF
NCAM signaling for neurite out-growth	4	8.7×	0.170	CACNA1C, CACNA1I, CACNB2, FGFR1
Transmission across Chemical Synapses	7	4.3×	0.170	SLC6A4, CACNB2, CACNA2D3, CHRNA3, CHRNB4, TUBB3, NRGN
Synthesis and processing of ENV and VPU	1	91.4×	0.192	FURIN
Dasatinib-resistant KIT mutants	1	91.4×	0.192	KIT
Imatinib-resistant KIT mutants	1	91.4×	0.192	KIT
KIT mutants bind TKIs	1	91.4×	0.192	KIT
Masitinib-resistant KIT mutants	1	91.4×	0.192	KIT
Nilotinib-resistant KIT mutants	1	91.4×	0.192	KIT
Regorafenib-resistant KIT mutants	1	91.4×	0.192	KIT
Signaling by kinase domain mutants of KIT	1	91.4×	0.192	KIT
Sunitinib-resistant KIT mutants	1	91.4×	0.192	KIT
Signaling by juxtamembrane domain KIT mutants	1	91.4×	0.192	KIT
Sorafenib-resistant KIT mutants	1	91.4×	0.192	KIT
Drug resistance of KIT mutants	1	91.4×	0.192	KIT
Signaling by extracellular domain mutants of KIT	1	91.4×	0.192	KIT
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	2	26.1×	0.192	CHRNA3, CHRNB4
Highly calcium permeable nicotinic acetylcholine receptors	2	20.3×	0.192	CHRNA3, CHRNB4
Activation of Ca-permeable Kainate Receptor	2	18.3×	0.192	GRIK2, GRIK3
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	2	18.3×	0.192	TFAP2B, TFAP2D
Role of second messengers in netrin-1 signaling	2	16.6×	0.192	TRPC4, DCC
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	2	16.6×	0.192	CHRNA3, CHRNB4
Presynaptic depolarization and calcium channel opening	2	15.2×	0.192	CACNB2, CACNA2D3
Presynaptic nicotinic acetylcholine receptors	2	15.2×	0.192	CHRNA3, CHRNB4
TP53 Regulates Transcription of Death Receptors and Ligands	2	15.2×	0.192	PPP1R13B, TMEM219
Activation of the TFAP2 (AP-2) family of transcription factors	2	15.2×	0.192	TFAP2B, TFAP2D
Acetylcholine binding and downstream events	2	13.1×	0.192	CHRNA3, CHRNB4
Postsynaptic nicotinic acetylcholine receptors	2	13.1×	0.192	CHRNA3, CHRNB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 205 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
postsynaptic modulation of chemical synaptic transmission	6	19.7×	6e-04	BRAF, SORCS3, DCC, DRD2, GRM3, NRGN
glutamate receptor signaling pathway	5	22.8×	0.001	GRID2, GRIK2, GRIK3, GRIN2A, KCNB1
negative regulation of synaptic transmission, glutamatergic	4	32.9×	0.002	DRD2, GRIK2, GRIK3, HCN1
obsolete signal peptide processing	4	27.4×	0.004	IMMP2L, CLN5, SPPL3, FURIN
cell surface receptor protein tyrosine phosphatase signaling pathway	3	30.8×	0.021	PTN, PTPRD, PTPRF
excitatory postsynaptic potential	5	10.8×	0.021	CHRNA3, DRD2, GRID2, GRIN2A, MEF2C
negative regulation of neuron apoptotic process	9	4.9×	0.021	BRAF, TFAP2B, TFAP2D, FAIM2, CLU, AMBRA1, GRIK2, MEF2C (+1 more)
negative regulation of relaxation of cardiac muscle	2	82.2×	0.024	PDE4B, PDE4D
regulation of synaptic plasticity	6	7.6×	0.024	SORCS3, CNTN4, GRIN2A, MEF2C, ATF4, PTN
nervous system development	14	3.1×	0.024	TCF4, TFAP2B, RBFOX1, CHRNA3, CNTN4, IGSF9B, LSAMP, MEF2C (+6 more)
pigmentation	4	13.7×	0.024	SZT2, DRD2, KIT, MC1R
habenula development	2	54.8×	0.045	NR4A2, PAX6
membrane depolarization during atrial cardiac muscle cell action potential	2	54.8×	0.045	CACNA1C, CACNB2
synaptic membrane adhesion	4	11.3×	0.045	CDH10, LRFN5, PTPRD, PTPRF
striatal medium spiny neuron differentiation	2	41.1×	0.050	BCL11B, ZSWIM6
hematopoietic stem cell migration	2	41.1×	0.050	BCL11B, KIT
negative regulation of heart contraction	2	41.1×	0.050	ATP2A2, PDE4D
synaptic transmission involved in micturition	2	41.1×	0.050	CHRNA3, CHRNB4
lncRNA transcription	2	41.1×	0.050	TOPAZ1, NFATC2
negative regulation of cellular response to hypoxia	2	41.1×	0.050	DDAH1, DRD2
positive regulation of synaptic transmission	3	16.4×	0.050	SORCS3, KCTD13, GRIK2
neuronal action potential	4	9.4×	0.050	CACNA1I, CHRNB4, GRIK2, HCN1
visual learning	5	7.5×	0.050	BRAF, TAFA2, DRD2, GRIN2A, KIT
memory	6	5.4×	0.050	SLC6A4, CSMD1, SORCS3, TAFA2, GRIN2A, PTN
modulation of chemical synaptic transmission	6	5.4×	0.050	CHMP2B, GRID2, GRIK2, GRIK3, NXPH4, PTPRD
positive regulation of neuron projection development	7	4.7×	0.050	NEGR1, ZNF804A, MARK2, FES, FGFR1, FUT9, PTN
positive regulation of axon regeneration	2	32.9×	0.074	BRAF, PTN
membrane depolarization during AV node cell action potential	2	32.9×	0.074	CACNA1C, CACNB2
regulation of postsynaptic density assembly	3	13.0×	0.074	FGFR1, GRID2, PTPRD
positive regulation of calcineurin-NFAT signaling cascade	3	11.7×	0.096	CAMTA1, SPPL3, AKAP6

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
Citalopram	Phase 3 (in late-stage trials)
Clomipramine	Phase 3 (in late-stage trials)
Cycloserine	Phase 3 (in late-stage trials)
Escitalopram	Phase 3 (in late-stage trials)
Fluoxetine	Phase 3 (in late-stage trials)
Fluvoxamine	Phase 3 (in late-stage trials)
Memantine	Phase 3 (in late-stage trials)
Paroxetine	Phase 3 (in late-stage trials)
Sertraline	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)
Troriluzole	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine, Agomelatine, Aripiprazole, Azithromycin, Bitopertin, Cannabidiol, Celecoxib, Flumazenil, Glycine, Ketamine, Levetiracetam, Methamphetamine, Midazolam, Minocycline, Naltrexone, Nitrogen, Nitrous Oxide, Ondansetron, Oxytocin, Paliperidone, Pramipexole, Quetiapine, Rapastinel, Riluzole, Risperidone, Secretin Synthetic Human, Sodium Chloride, Tolcapone, Xenon.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 8 · Phased (≥1): 11 · Undrugged: 64

Druggability breadth: 69 of 229 evidence-associated genes (30%) 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
SLC6A4	CETIRIZINE
SHMT2	OXAPROZIN
BRAF	VEMURAFENIB
SRPK2	FEDRATINIB
CACNA1C	REMIFENTANIL
CACNA1I	NIMODIPINE
CACNB2	NIMODIPINE
CACNA2D3	NIMODIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A4	422	4
CACNA1C	85	4
BRAF	48	4
SRPK2	11	4
SHMT2	7	4
CACNA1I	7	4
CACNB2	2	4
CACNA2D3	2	4
TCF4	1	2
TRPC4	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	CACNA1C, SLC6A4
CLOTRIMAZOLE	4	CACNA1C, SLC6A4
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	CACNA1C, SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	BRAF, SLC6A4
DESLORATADINE	4	SLC6A4
DULOXETINE	4	CACNA1C, SHMT2, SLC6A4
CELECOXIB	4	SLC6A4
UMECLIDINIUM	4	SLC6A4
PALONOSETRON	4	SLC6A4
PHENIRAMINE	4	SLC6A4
VILANTEROL	4	SLC6A4
ESCITALOPRAM OXALATE	4	SLC6A4
TIOCONAZOLE	4	SLC6A4
NEFAZODONE HYDROCHLORIDE	4	SLC6A4
ETHYLESTRENOL	4	SLC6A4
CALCIPOTRIENE	4	SLC6A4
CINACALCET HYDROCHLORIDE	4	SLC6A4
CITALOPRAM HYDROBROMIDE	4	SLC6A4
NORGESTIMATE	4	SLC6A4
VENLAFAXINE HYDROCHLORIDE	4	SLC6A4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
SLC6A4	1,055	Binding:1021, Functional:18, ADMET:9, Toxicity:6, Unclassified:1
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
SRPK2	221	Binding:221
CACNA1I	56	Binding:44, Functional:9, ADMET:3
TCF4	31	Binding:31
TRPC4	22	Binding:18, ADMET:4
CACNB2	22	Binding:20, ADMET:1, Toxicity:1
KDM3B	13	Binding:13
CACNA2D3	13	Binding:13
KCTD12	12	Binding:12
SALL4	12	Binding:12
ACTR5	7	Binding:7
SHMT2	6	Binding:6
OTUD7B	6	Binding:6
ATXN7	5	Binding:5
TXNL1	2	Binding:2
OSBPL3	1	Binding:1
AS3MT	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CNNM4	7.2.2.14	P-type Mg2+ transporter
SHMT2	2.1.2.1	glycine hydroxymethyltransferase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
TCF4	7.6.2.3	ABC-type glutathione-S-conjugate transporter
KDM3B	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase
ATP9A	7.6.2.1	P-type phospholipid transporter
AS3MT	2.1.1.137	arsenite methyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SLC6A4	1,055
BRAF	1,442
SRPK2	221
CACNA1C	575

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
SLC6A4	1

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)
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	CACNA1C, SLC6A4
CLOTRIMAZOLE	4	CACNA1C, SLC6A4
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	CACNA1C, SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	BRAF, SLC6A4
DESLORATADINE	4	SLC6A4
CELECOXIB	4	SLC6A4
UMECLIDINIUM	4	SLC6A4
PALONOSETRON	4	SLC6A4
PHENIRAMINE	4	SLC6A4
VILANTEROL	4	SLC6A4
ESCITALOPRAM OXALATE	4	SLC6A4
TIOCONAZOLE	4	SLC6A4
NEFAZODONE HYDROCHLORIDE	4	SLC6A4
ETHYLESTRENOL	4	SLC6A4
CALCIPOTRIENE	4	SLC6A4
CINACALCET HYDROCHLORIDE	4	SLC6A4
CITALOPRAM HYDROBROMIDE	4	SLC6A4
NORGESTIMATE	4	SLC6A4
VENLAFAXINE HYDROCHLORIDE	4	SLC6A4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	SLC6A4, SHMT2, BRAF, SRPK2, CACNA1C, CACNA1I, CACNB2, CACNA2D3
B	Phased (≥1) drug, not yet approved	3	TCF4, TRPC4, ACTR5
C	Druggable family + PDB, no drug	7	CNNM4, KDM3B, CSMD1, MOB4, NEGR1, AS3MT, CAMTA1
D	Druggable family + AlphaFold only, no drug	5	FOLH1B, IMMP2L, SORCS3, VSIG2, SLC45A1
E	Difficult family or no structure, no drug	52	RGS6, RNU6-1, CNNM2, RTN1, ATXN7, SOX5, BTF3P11, TCF20, ELP4, TFAP2B (+42 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RGS6	0	—
RNU6-1	0	—
CNNM2	0	—
RTN1	0	—
CNNM4	0	—
ATXN7	5	—
SOX5	0	—
BTF3P11	0	—
TCF20	0	—
ELP4	0	—
TFAP2B	0	—
TXNL1	2	—
BCL11B	0	—
SLC30A9	0	—
FAM53C	0	—
KDM3B	13	—
PCLO	0	—
WDR7	0	—
ATP9A	0	—
FBXL3	0	—
FOLH1B	0	—
ZKSCAN3	0	—
CSMD1	0	—
ZSCAN31	0	—
PMEPA1	0	—
PCDH18	0	—
IFT81	0	—
MRPL33	0	—
VPS45	0	—
IMMP2L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 618.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	445
PHASE2	66
PHASE4	36
PHASE3	24
PHASE1/PHASE2	17
PHASE1	17
PHASE2/PHASE3	7
EARLY_PHASE1	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00640133	PHASE4	ACTIVE_NOT_RECRUITING	Effectiveness of Deep Brain Stimulation for Treating People With Treatment Resistant Obsessive-Compulsive Disorder
NCT04336228	PHASE4	ACTIVE_NOT_RECRUITING	The Role of Serotonin in Compulsive Behavior in Humans: Underlying Brain Mechanisms
NCT06956157	PHASE4	ACTIVE_NOT_RECRUITING	NAC for Treatment-Resistant OCD and Other Related Disorders
NCT00000373	PHASE4	COMPLETED	Treatment of Obsessive-Compulsive Disorder
NCT00001658	PHASE4	COMPLETED	Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections
NCT00116532	PHASE4	COMPLETED	Escitalopram for the Treatment of Obsessive Compulsive Disorder (OCD)
NCT00182520	PHASE4	COMPLETED	Efficacy of Adding Topiramate to Current Treatment in Refractory Obsessive Compulsive Disorder (OCD)
NCT00182533	PHASE4	TERMINATED	Sertraline in Generalized Social Phobia With Co-Occurring Anxiety and Mood Disorders
NCT00211744	PHASE4	COMPLETED	Topiramate Augmentation in the Treatment of Obsessive-Compulsive Disorder
NCT00352469	PHASE4	COMPLETED	Trial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety
NCT00352768	PHASE4	TERMINATED	Fluvoxamine Maleate in the Treatment of Obsessive-Compulsive Disorder: A Post-marketing Clinical Study in Children and Adolescents
NCT00382291	PHASE4	COMPLETED	Effectiveness of Sertraline and Cognitive Behavioral Therapy in Treating Pediatric Obsessive-Compulsive Disorder
NCT00464698	PHASE4	COMPLETED	Duloxetine for the Treatment of Obsessive Compulsive Disorder (OCD)
NCT00466609	PHASE4	COMPLETED	Using Drug Augmentation to Treat Obsessive Compulsive Disorder Patients Who Did Not Respond to Previous Treatment
NCT00564564	PHASE4	COMPLETED	Quetiapine Augmentation Versus Clomipramine Augmentation of SSRI for Obsessive-compulsive Disorder Patients
NCT00680602	PHASE4	COMPLETED	Group Cognitive Behavioral Therapy Versus Fluoxetine for Obsessive-Compulsive Disorder: a Practical Trial
NCT00708240	PHASE4	UNKNOWN	Treatment Youth With Obsessive-Compulsive Disorder
NCT00708396	PHASE4	UNKNOWN	Tolerability And Efficacy Of High Dose Escitalopram In The Treatment Of Patients Suffering From Schizophrenia And Obsessive-Compulsive Disorder (OCD) - An Open Label Study
NCT00723060	PHASE4	COMPLETED	Comparison of Effects Between Conventional Dose and High Dose Escitalopram on Clinical Improvement in Patients With Obsessive-compulsive Disorder
NCT00743834	PHASE4	UNKNOWN	Cost-Effectiveness of Adding Web-Based Cognitive-Behavioral Therapy (CBT) to Luvox CR for Obsessive Compulsive Disorder (OCD)
NCT00796497	PHASE4	COMPLETED	Ondansetron in Treatment Resistant Obsessive Compulsive Disorder (OCD)
NCT00994786	PHASE4	COMPLETED	A Study of Pregabalin (Lyrica) Augmentation in Serotonin Reuptake Inhibitor-Refractory Obsessive Compulsive Disorder
NCT01135745	PHASE4	COMPLETED	Deep Brain Stimulation for Obsessive Compulsive Disorder (OCD PMCF)
NCT01303536	PHASE4	COMPLETED	Ondansetron Augmentation in Treatment-resistant OCD
NCT01649895	PHASE4	COMPLETED	D-Cycloserine as an Adjunct to Internet-CBT for OCD
NCT02022709	PHASE4	COMPLETED	Efficacy of Exposure and Response Prevention(ERP) and SSRIs in Chinese OCD Patients
NCT02194075	PHASE4	COMPLETED	Methylphenidate Hydrochloride Controlled-Release Tablets Augmentation Strategy for Patients With Obsessive Compulsive Disorder
NCT02334644	PHASE4	TERMINATED	Probiotic Treatment in Adult Obsessive-Compulsive Disorder
NCT02656342	PHASE4	COMPLETED	Translational Approach to the Understanding and Treatment of Obsessive-Compulsive Disorder (OCD). Can D-Cycloserine Enhance and Stabilize the Treatment-response in Relapsed and Non-responding OCD-patients?
NCT02790710	PHASE4	WITHDRAWN	Brief Intervention for OCD Fears
NCT03068429	PHASE4	COMPLETED	Fear Conditioned Response in Healthy Subjects and in OCD Patients Pre and Post Treatment With Sertraline.
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT03993535	PHASE4	COMPLETED	Predicting Treatment Response in Patients With OCD
NCT04015596	PHASE4	TERMINATED	Trial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS
NCT04963257	PHASE4	UNKNOWN	Sertraline Combined With Fluvoxamine in the Treatment of Refractory Obsessive-compulsive Disorder
NCT06231095	PHASE4	COMPLETED	Does TMS Affect Neuroplasticity? The Role of Brain-derived Neurotrophic Factor and Neuronal Cell Adhesion Molecules - an Intensive Clinical Protocol Among Patients With Obsessive-compulsive Disorders
NCT05659082	PHASE3	ENROLLING_BY_INVITATION	Ventral Capsulotomy for Intractable OCD
NCT00000384	PHASE3	COMPLETED	Treatment of Obsessive-Compulsive Disorder (OCD) in Children
NCT00000386	PHASE3	COMPLETED	Behavior Therapy for Children and Adolescents With Obsessive-Compulsive Disorder (OCD)
NCT00000389	PHASE3	COMPLETED	Treatment for Anxiety in Children

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUVOXAMINE	4	24
FLUOXETINE	4	10
CYCLOSERINE	4	9
ONDANSETRON	4	9
SERTRALINE	4	8
QUETIAPINE	4	5
CLOMIPRAMINE	4	4
ESCITALOPRAM	4	4
PAROXETINE	4	4
CITALOPRAM	4	3
PRAMIPEXOLE	4	3
TOPIRAMATE	4	3
GLYCINE	4	2
KETAMINE HYDROCHLORIDE	4	2
MEMANTINE	4	2
MINOCYCLINE	4	2
NABILONE	4	2
RILUZOLE	4	2
TOLCAPONE	4	2
ACETYLCYSTEINE	4	1
AMISULPRIDE	4	1
AMOXICILLIN	4	1
DEXTROMETHORPHAN	4	1
DEXTROMETHORPHAN HYDROBROMIDE	4	1
DRONABINOL	4	1
DULOXETINE	4	1
FLUMAZENIL	4	1
HUMAN IMMUNOGLOBULIN G	4	1
LAMOTRIGINE	4	1
LEVETIRACETAM	4	1