Tuberculosis

Summary

Tuberculosis (MONDO:0018076) is a disease (an umbrella term covering 12 Mondo subtypes) with 69 cohort genes (173 GWAS associations across 47 studies) and 952 clinical trials. The dominant Reactome pathway is Translocation of ZAP-70 to Immunological synapse (3 cohort genes). Top therapeutic interventions include isoniazid, pyridoxine, and pyrazinamide.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 69
• GWAS associations: 173
• Clinical trials: 952

Clinical features

Epidemiology

Prevalence records

40 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	>1 / 1000	139	Worldwide	Validated
Annual incidence	1-9 / 100 000	9	Europe	Validated
Point prevalence	1-5 / 10 000	16	Europe	Validated
Annual incidence	1-9 / 100 000	4	Greece	Validated
Annual incidence	1-9 / 100 000	5	Iceland	Validated
Annual incidence	1-9 / 100 000	6	Israel	Validated
Annual incidence	1-5 / 10 000	15	Spain	Validated
Annual incidence	1-5 / 10 000	24	Portugal	Validated
Annual incidence	1-9 / 100 000	8	Belgium	Validated
Annual incidence	1-9 / 100 000	4	Austria	Validated
Annual incidence	6-9 / 10 000	90	Algeria	Validated
Annual incidence	1-5 / 10 000	23	Poland	Validated
Annual incidence	1-5 / 10 000	42	Latvia	Validated
Annual incidence	1-5 / 10 000	59	Lithuania	Validated
Annual incidence	1-5 / 10 000	49	Bosnia and Herzegovina	Validated
Annual incidence	1-5 / 10 000	17	Croatia	Validated
Annual incidence	>1 / 1000	101	Romania	Validated
Annual incidence	6-9 / 10 000	97	Russian Federation	Validated
Annual incidence	1-9 / 100 000	3.4	United States	Validated
Annual incidence	1-5 / 10 000	20	Japan	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	tuberculosis
Mondo ID	MONDO:0018076
MeSH	D014376
Orphanet	3389
DOID	DOID:399
ICD-10-CM	A15-A19
ICD-11	2072728114
NCIT	C3423
SNOMED CT	56717001
UMLS	C0041296
MedGen	22513
GARD	0007827
MedDRA	10044755
NORD	1801
Is cancer (heuristic)	no

Also known as: active tuberculosis · Kochs disease · TB · tuberculosis disease

Data availability: 173 GWAS associations (47 studies).

Disease family

An umbrella term covering 12 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › bacterial infectious disease › primary bacterial infectious disease › tuberculosis

Related subtypes (36): Buruli ulcer disease, sennetsu fever, salmonellosis, pinta disease, chancroid, gonorrhea, anthrax infection, leprosy, botulism, diphtheria, tetanus, bartonellosis, brucellosis, campylobacteriosis, glanders, granuloma inguinale, legionellosis, leptospirosis, listeriosis, Mycobacterium avium complex disease, ornithosis, rhinoscleroma, staphyloenterotoxemia, syphilis, cholera, ehrlichiosis, melioidosis, tularemia, plague, Q fever, shigellosis, Lyme disease, relapsing fever, spirillary rat-bite fever, streptobacillary rat-bite fever, Borrelia miyamotoi disease

Subtypes (12): extrapulmonary tuberculosis, pulmonary tuberculosis, endocrine tuberculosis, tuberculoma, latent tuberculosis infection, drug-resistant tuberculosis, active tuberculosis, tuberculous encephalopathy, primary tuberculous lymphadenitis, primary bone and joint tuberculosis, multifocal tuberculosis, primary tuberculosis of the digestive system

Genetics & variants

GWAS landscape

173 GWAS associations across 47 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1823897	7e-14	RPS24P21 - LINC01546 x FRMPD4	?
rs532003101	1e-13	SERPINA9 - SERPINA12	C	2.95
rs2057178	1e-12	THEM7P - WT1	?
rs426247	2e-12	TAB3 - FTHL17 x PCDH11X	?
rs2112508	3e-12	ISCA1P1 - HTR1A x THAP12P3 - LNCAROD	?
rs1347075	3e-12	RBMX2P4 - ETV1 x PPP1R3B-DT	?
rs75609205	3e-12	MYT1L	A	2.33
rs7971813	3e-12	PPFIA2-AS1, PPFIA2	A	2.88
rs4733781	4e-12	ASAP1	A
rs5991619	6e-12	IMPDH1P4 - NANOGP10 x UBE2V1P9 - RNU6-555P	?
rs7991005	6e-12	GPC6 x LPCAT2	?
rs11094800	7e-12	LINC03070 x PCDH11X	?
rs7341174	8e-12	LINC02208, LINC02147 x SYT1	?
rs68046754	8e-12	PCDH11X x MAGEC1 - MAGEC2	?
rs4240897	1e-11	MFN2	?	1.27
rs6694239	1e-11	TNR - LINC01657 x SPATS2L	?
rs4824843	1e-11	FUNDC1 - CHTF8P1 x PCDH11X	?
rs2170314	1e-11	DIAPH2-AS1 - NCKAP1P1 x DIAPH2-AS1 - NCKAP1P1	?
rs564904244	1e-11	CDC14C - DDX43P2	G	2.71
rs12437118	2e-11	ESRRB - CYCSP1	A	1.28
rs6114027	2e-11	TGM6	C	1.34
rs5972637	2e-11	DMD x UBE2V1P9 - RNU6-555P	?
rs1352015	2e-11	EDA2R x PCDH11X	?
rs554596237	2e-11	KDM4C	G	1.09
rs5916341	3e-11	NLGN4X x PCDH11X	?
rs3072699	3e-11	NLGN4X x PCDH11X	?
rs191653573	5e-11	HNRNPA1P47 - LINC01821	G	2.67
rs1495741	7e-11	NAT2 - PSD3	A	6.01
rs41553512	8e-11	HLA-DRB5	?	2.14
rs570545343	1e-10	NLN - ERBIN	A	1.06

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002810	Curtis J	2015	5,530	5,607	Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration.
GCST90473018	UK Biobank Whole-Genome Sequencing Consortium	2025	2,516	455,924	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90038710	Donertas HM	2021	2,473	482,125	Common genetic associations between age-related diseases.
GCST000764	Thye T	2010	2,237	3,122	Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2.
GCST90077846	Backman JD	2021	2,209	329,545	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081832	Backman JD	2021	2,209	329,545	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST008488	Luo Y	2019	2,160	1,820	Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians.
GCST90077847	Backman JD	2021	2,076	326,976	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081833	Backman JD	2021	2,076	326,976	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90726832	Kim HI	2026	1,556	42,470	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	34
low_freq (0.01-0.05)	8
rare (<0.01)	7
unknown	1

Functional consequences

Consequence	Count
intron_variant	19
intergenic_variant	12
intron_variant x intron_variant	9
intergenic_variant x intron_variant	3
missense_variant	3
intergenic_variant x intergenic_variant	2
intron_variant x intergenic_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1823897	X x X	3164354	G>A,C,T	0.05	intergenic_variant x intron_variant	RPS24P21 - LINC01546 x FRMPD4	7e-14	Tier 4: intronic/intergenic
rs532003101	14	94485337	C>T	0	intergenic_variant	SERPINA9 - SERPINA12	1e-13	Tier 4: intronic/intergenic
rs2057178	11	32342641	G>A,C,T	0.05	intron_variant	THEM7P - WT1	1e-12	Tier 4: intronic/intergenic
rs426247	X x X	31060417	C>T	0.05	intron_variant x intron_variant	TAB3 - FTHL17 x PCDH11X	2e-12	Tier 4: intronic/intergenic
rs2112508	5 x 10	63465907	C>A,T	0.05	intergenic_variant x intergenic_variant	ISCA1P1 - HTR1A x THAP12P3 - LNCAROD	3e-12	Tier 4: intronic/intergenic
rs1347075	7 x 8	13480818	A>C,T	0.05	intron_variant x intron_variant	RBMX2P4 - ETV1 x PPP1R3B-DT	3e-12	Tier 4: intronic/intergenic
rs75609205	2	2156032	G>A	0.05	intron_variant	MYT1L	3e-12	Tier 4: intronic/intergenic
rs7971813	12	81304971	A>C,G	0	intron_variant	PPFIA2-AS1, PPFIA2	3e-12	Tier 4: intronic/intergenic
rs4733781	8	130284521	A>C	0.313	intron_variant	ASAP1	4e-12	Tier 4: intronic/intergenic
rs5991619	X x X	43287584	C>A,G,T	0.05	intron_variant x intergenic_variant	IMPDH1P4 - NANOGP10 x UBE2V1P9 - RNU6-555P	6e-12	Tier 4: intronic/intergenic
rs7991005	13 x 16	94382101	C>G,T	0.05	intron_variant x intron_variant	GPC6 x LPCAT2	6e-12	Tier 4: intronic/intergenic
rs11094800	X x X	5693674	T>A,C,G	0.05	intron_variant x intron_variant	LINC03070 x PCDH11X	7e-12	Tier 4: intronic/intergenic
rs7341174	5 x 12	118256646	C>A,T	0.05	intron_variant x intron_variant	LINC02208, LINC02147 x SYT1	8e-12	Tier 4: intronic/intergenic
rs68046754	X x X	92573550	C>T	0.05	intron_variant x intron_variant	PCDH11X x MAGEC1 - MAGEC2	8e-12	Tier 4: intronic/intergenic
rs4240897	1	11982698	G>A,T	0.493	intron_variant	MFN2	1e-11	Tier 4: intronic/intergenic
rs6694239	1 x 2	175755086	G>C	0.05	intergenic_variant x intron_variant	TNR - LINC01657 x SPATS2L	1e-11	Tier 4: intronic/intergenic
rs4824843	X x X	44617664	A>G,T	0.05	intergenic_variant x intron_variant	FUNDC1 - CHTF8P1 x PCDH11X	1e-11	Tier 4: intronic/intergenic
rs2170314	X x X	97753578	G>A,C	0.05	intergenic_variant x intergenic_variant	DIAPH2-AS1 - NCKAP1P1 x DIAPH2-AS1 - NCKAP1P1	1e-11	Tier 4: intronic/intergenic
rs564904244	7	48999618	G>A	0	intergenic_variant	CDC14C - DDX43P2	1e-11	Tier 4: intronic/intergenic
rs12437118	14	76517387	G>A,C	0.261	intron_variant	ESRRB - CYCSP1	2e-11	Tier 4: intronic/intergenic
rs6114027	20	2398952	T>C	0.158	intron_variant	TGM6	2e-11	Tier 4: intronic/intergenic
rs5972637	X x X	32656919	C>T	0.05	intron_variant x intergenic_variant	DMD x UBE2V1P9 - RNU6-555P	2e-11	Tier 4: intronic/intergenic
rs1352015	X x X	66624001	G>A	0.05	intron_variant x intron_variant	EDA2R x PCDH11X	2e-11	Tier 4: intronic/intergenic
rs554596237	9	6953063	T>G	0.006	intron_variant	KDM4C	2e-11	Tier 4: intronic/intergenic
rs5916341	X x X	6217939	C>T	0.05	intron_variant x intron_variant	NLGN4X x PCDH11X	3e-11	Tier 4: intronic/intergenic
rs3072699	X x X	6218474	C>A,G	0.05	intron_variant x intron_variant	NLGN4X x PCDH11X	3e-11	Tier 4: intronic/intergenic
rs191653573	2	194278463	G>T	0.001	intergenic_variant	HNRNPA1P47 - LINC01821	5e-11	Tier 4: intronic/intergenic
rs1495741	8	18415371	G>A	0.41	intergenic_variant	NAT2 - PSD3	7e-11	Tier 4: intronic/intergenic
rs41553512	6	32518625	C>G,T	0.016	missense_variant	HLA-DRB5	8e-11	Tier 1: coding
rs570545343	5	65876162	G>A	0.015	intergenic_variant	NLN - ERBIN	1e-10	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 82 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SALL2	Orphanet:98942	Coloboma of choroid and retina
SALL2	Orphanet:98943	Coloboma of eye lens
SALL2	Orphanet:98944	Coloboma of iris
SALL2	Orphanet:98945	Coloboma of macula
SALL2	Orphanet:98946	Coloboma of eyelid
SALL2	Orphanet:98947	Coloboma of optic disc
SALL2	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
SOX11	Orphanet:1465	Coffin-Siris syndrome
BTNL2	Orphanet:797	Sarcoidosis
TNFRSF1B	Orphanet:2584	Classic mycosis fungoides
TNFRSF1B	Orphanet:3162	Sézary syndrome
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
TGM6	Orphanet:276193	Spinocerebellar ataxia type 35
TGM6	Orphanet:319465	Inherited acute myeloid leukemia
ZFPM2	Orphanet:2140	Congenital diaphragmatic hernia
ZFPM2	Orphanet:251510	46,XY partial gonadal dysgenesis
ZFPM2	Orphanet:3303	Tetralogy of Fallot
MFN2	Orphanet:2398	Multiple symmetric lipomatosis
MFN2	Orphanet:64751	Hereditary motor and sensory neuropathy type 5
MFN2	Orphanet:90118	Severe early-onset axonal neuropathy due to MFN2 deficiency
MFN2	Orphanet:90120	Hereditary motor and sensory neuropathy type 6
MFN2	Orphanet:99947	Autosomal dominant Charcot-Marie-Tooth disease type 2A2
CLCN6	Orphanet:610573	CLCN6-related childhood-onset progressive neurodegeneration-peripheral neuropathy syndrome
SMOC1	Orphanet:1106	Microphthalmia with limb anomalies
VPS13C	Orphanet:2828	Young-onset Parkinson disease
NAA60	Orphanet:1980	Bilateral striopallidodentate calcinosis
DYNC2H1	Orphanet:474	Jeune syndrome
DYNC2H1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
DYNC2H1	Orphanet:93270	Short rib-polydactyly syndrome, Saldino-Noonan type
DYNC2H1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
ESRRB	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
GATA6	Orphanet:2140	Congenital diaphragmatic hernia
GATA6	Orphanet:2255	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
GATA6	Orphanet:3303	Tetralogy of Fallot
GATA6	Orphanet:334	Hereditary atrial fibrillation
GATA6	Orphanet:665044	Common arterial trunk with aortic dominance
GATA6	Orphanet:665058	Common arterial trunk with pulmonary dominance and interrupted aortic arch
GATA6	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA6	Orphanet:99103	Atrial septal defect, ostium secundum type
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid

Cohort genes → proteins

69 cohort genes, 63 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	69

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SALL2	HGNC:10526	ENSG00000165821	Q9Y467	Sal-like protein 2	gwas
SLC6A4	HGNC:11050	ENSG00000108576	P31645	Sodium-dependent serotonin transporter	gwas
SOX11	HGNC:11191	ENSG00000176887	P35716	Transcription factor SOX-11	gwas
SPON1	HGNC:11252	ENSG00000262655	Q9HCB6	Spondin-1	gwas
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
TNFRSF1B	HGNC:11917	ENSG00000028137	P20333	Tumor necrosis factor receptor superfamily member 1B	gwas
TNFRSF8	HGNC:11923	ENSG00000120949	P28908	Tumor necrosis factor receptor superfamily member 8	gwas
C2CD2	HGNC:1266	ENSG00000157617	Q9Y426	C2 domain-containing protein 2	gwas
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	gwas
SLC38A1	HGNC:13447	ENSG00000111371	Q9H2H9	Sodium-coupled neutral amino acid symporter 1	gwas
DMRTA1	HGNC:13826	ENSG00000176399	Q5VZB9	Doublesex- and mab-3-related transcription factor A1	gwas
PRND	HGNC:15748	ENSG00000171864	Q9UKY0	Prion-like protein doppel	gwas
TGM6	HGNC:16255	ENSG00000166948	O95932	Protein-glutamine gamma-glutamyltransferase 6	gwas
ZFPM2	HGNC:16700	ENSG00000169946	Q8WW38	Zinc finger protein ZFPM2	gwas
TENT4A	HGNC:16705	ENSG00000112941	Q5XG87	Terminal nucleotidyltransferase 4A	gwas
MFN2	HGNC:16877	ENSG00000116688	O95140	Mitofusin-2	gwas
DPF3	HGNC:17427	ENSG00000205683	Q92784	Zinc finger protein DPF3	gwas
DROSHA	HGNC:17904	ENSG00000113360	Q9NRR4	Ribonuclease 3	gwas
CNOT6L	HGNC:18042	ENSG00000138767	Q96LI5	CCR4-NOT transcription complex subunit 6-like	gwas
HCG23	HGNC:19713			HLA complex group 23	gwas
CLCN6	HGNC:2024	ENSG00000011021	P51797	H(+)/Cl(-) exchange transporter 6	gwas
SMOC1	HGNC:20318	ENSG00000198732	Q9H4F8	SPARC-related modular calcium-binding protein 1	gwas
C6orf118	HGNC:21233	ENSG00000112539	Q5T5N4	Uncharacterized protein C6orf118	gwas
VPS13C	HGNC:23594	ENSG00000129003	Q709C8	Intermembrane lipid transfer protein VPS13C	gwas
E2F7	HGNC:23820	ENSG00000165891	Q96AV8	Transcription factor E2F7	gwas
CTAGE1	HGNC:24346	ENSG00000212710	Q96RT6	cTAGE family member 2	gwas
GRAMD2B	HGNC:24911	ENSG00000155324	Q96HH9	GRAM domain-containing protein 2B	gwas
CABLES1	HGNC:25097	ENSG00000134508	Q8TDN4	CDK5 and ABL1 enzyme substrate 1	gwas
MIIP	HGNC:25715	ENSG00000116691	Q5JXC2	Migration and invasion-inhibitory protein	gwas
NAA60	HGNC:25875	ENSG00000122390	Q9H7X0	N-alpha-acetyltransferase 60	gwas
CYP2C8	HGNC:2622	ENSG00000138115	P10632	Cytochrome P450 2C8	gwas
CFAP54	HGNC:26456	ENSG00000188596	Q96N23	Cilia- and flagella-associated protein 54	gwas
LINC00955	HGNC:26644	ENSG00000216560		long intergenic non-protein coding RNA 955	gwas
LINC03122	HGNC:26744	ENSG00000178722	Q2M2E5	Uncharacterized protein encoded by LINC03122	gwas
PLD5	HGNC:26879	ENSG00000180287	Q8N7P1	Inactive phospholipase D5	gwas
RNF187	HGNC:27146	ENSG00000168159	Q5TA31	E3 ubiquitin-protein ligase RNF187	gwas
ASAP1	HGNC:2720	ENSG00000153317	Q9ULH1	Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1	gwas
UBLCP1	HGNC:28110	ENSG00000164332	Q8WVY7	Ubiquitin-like domain-containing CTD phosphatase 1	gwas
DCUN1D5	HGNC:28409	ENSG00000137692	Q9BTE7	DCN1-like protein 5	gwas
KIAA2013	HGNC:28513	ENSG00000116685	Q8IYS2	Uncharacterized protein KIAA2013	gwas
VWA8	HGNC:29071	ENSG00000102763	A3KMH1	von Willebrand factor A domain-containing protein 8	gwas
DYNC2H1	HGNC:2962	ENSG00000187240	Q8NCM8	Cytoplasmic dynein 2 heavy chain 1	gwas
DSCAM	HGNC:3039	ENSG00000171587	O60469	Cell adhesion molecule DSCAM	gwas
SNORD114-31	HGNC:33019	ENSG00000200089		small nucleolar RNA, C/D box 114-31	gwas
MSANTD1	HGNC:33741	ENSG00000188981	Q6ZTZ1	Myb/SANT-like DNA-binding domain-containing protein 1	gwas
AGMO	HGNC:33784	ENSG00000187546	Q6ZNB7	Alkylglycerol monooxygenase	gwas
ESRRB	HGNC:3473	ENSG00000119715	O95718	Steroid hormone receptor ERR2	gwas
NCS1	HGNC:3953	ENSG00000107130	P62166	Neuronal calcium sensor 1	gwas
GATA6	HGNC:4174	ENSG00000141448	Q92908	Transcription factor GATA-6	gwas
GLO1	HGNC:4323	ENSG00000124767	Q04760	Lactoylglutathione lyase	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SALL2	Sal-like protein 2	Probable transcription factor that plays a role in eye development before, during, and after optic fissure closure.
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.
SOX11	Transcription factor SOX-11	Transcription factor that acts as a transcriptional activator.
SPON1	Spondin-1	Cell adhesion protein that promotes the attachment of spinal cord and sensory neuron cells and the outgrowth of neurites in vitro.
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
TNFRSF1B	Tumor necrosis factor receptor superfamily member 1B	Receptor with high affinity for TNFSF2/TNF and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha.
TNFRSF8	Tumor necrosis factor receptor superfamily member 8	Receptor for TNFSF8/CD30L.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
SLC38A1	Sodium-coupled neutral amino acid symporter 1	Symporter that cotransports short-chain neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane.
PRND	Prion-like protein doppel	Required for normal acrosome reaction and for normal male fertility.
TGM6	Protein-glutamine gamma-glutamyltransferase 6	Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.
ZFPM2	Zinc finger protein ZFPM2	Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis.
TENT4A	Terminal nucleotidyltransferase 4A	Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3’ poly(A) tail creating a heterogeneous 3’ poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation.
MFN2	Mitofusin-2	Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion.
DPF3	Zinc finger protein DPF3	Belongs to the neuron-specific chromatin remodeling complex (nBAF complex).
DROSHA	Ribonuclease 3	Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis.
CNOT6L	CCR4-NOT transcription complex subunit 6-like	Has 3’-5’ poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate.
CLCN6	H(+)/Cl(-) exchange transporter 6	Voltage-gated channel mediating the exchange of chloride ions against protons.
SMOC1	SPARC-related modular calcium-binding protein 1	Plays essential roles in both eye and limb development.
VPS13C	Intermembrane lipid transfer protein VPS13C	Mediates the transfer of lipids between membranes at organelle contact sites.
E2F7	Transcription factor E2F7	Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response.
CABLES1	CDK5 and ABL1 enzyme substrate 1	Cyclin-dependent kinase binding protein.
MIIP	Migration and invasion-inhibitory protein	Inhibits glioma cells invasion and down-regulates adhesion- and motility-associated genes such as NFKB2 and ICAM1.
NAA60	N-alpha-acetyltransferase 60	N-alpha-acetyltransferase that specifically mediates the acetylation of N-terminal residues of the transmembrane proteins, with a strong preference for N-termini facing the cytosol.
CYP2C8	Cytochrome P450 2C8	A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins.
CFAP54	Cilia- and flagella-associated protein 54	Required for assembly and function of cilia and flagella.
RNF187	E3 ubiquitin-protein ligase RNF187	E3 ubiquitin-protein ligase that acts as a coactivator of JUN-mediated gene activation in response to growth factor signaling via the MAP3K1 pathway, independently from MAPK8.
ASAP1	Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1	Possesses phosphatidylinositol 4,5-bisphosphate-dependent GTPase-activating protein activity for ARF1 (ADP ribosylation factor 1) and ARF5 and a lesser activity towards ARF6.
UBLCP1	Ubiquitin-like domain-containing CTD phosphatase 1	Dephosphorylates 26S nuclear proteasomes, thereby decreasing their proteolytic activity.
DCUN1D5	DCN1-like protein 5	Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes which is necessary for the activation of cullin-RING E3 ubiqu…
VWA8	von Willebrand factor A domain-containing protein 8	Exhibits ATPase activity in vitro.
DYNC2H1	Cytoplasmic dynein 2 heavy chain 1	May function as a motor for intraflagellar retrograde transport.
DSCAM	Cell adhesion molecule DSCAM	Cell adhesion molecule that plays a role in neuronal self-avoidance.
AGMO	Alkylglycerol monooxygenase	Glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids.
ESRRB	Steroid hormone receptor ERR2	Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5’TCAAGGTCA-3’ localized on promoter and enhancer of targets genes regulating their expression or their transcription activity.
NCS1	Neuronal calcium sensor 1	Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner.
GATA6	Transcription factor GATA-6	Transcriptional activator.
GLO1	Lactoylglutathione lyase	Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB5	HLA class II histocompatibility antigen, DR beta 5 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
IL12B	Interleukin-12 subunit beta	Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.
IL2RB	Interleukin-2 receptor subunit beta	Receptor for interleukin-2.
IL6	Interleukin-6	Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism.
LRPAP1	Alpha-2-macroglobulin receptor-associated protein	Molecular chaperone for LDL receptor-related proteins that may regulate their ligand binding activity along the secretory pathway.
MTHFR	Methylenetetrahydrofolate reductase (NADPH)	Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.
NPPA	Natriuretic peptides A	Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism.
NPPB	Natriuretic peptides B	Cardiac hormone that plays a key role in mediating cardio-renal homeostasis.
PCSK6	Proprotein convertase subtilisin/kexin type 6	Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif.

Protein-family classification

Druggable: 21 · Difficult: 9 · Unknown: 39 · Druggable fraction: 0.3

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
Antibody/Immunoglobulin	9	3.8×	0.004
Nuclear receptor	1	5.6×	0.438
Enzyme (other)	9	1.6×	0.438
Phosphatase	1	1.2×	0.902
Other/Unknown	39	1.0×	0.902
Transcription factor	7	0.8×	0.915
Protease	1	0.5×	0.915
Scaffold/PPI	2	0.5×	0.915

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SALL2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
SLC6A4	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_serotonin_N, SNS_sf
SOX11	Transcription factor	no		HMG_box_dom, SOX-12/11/4, HMG_box_dom_sf
SPON1	Other/Unknown	no		TSP1_rpt, Reeler_dom, Spondin_N
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
TNFRSF1B	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_1B, TNFRSF1B_N
TNFRSF8	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_8, TNFRSF8_N
C2CD2	Other/Unknown	no		C2_dom, C2_domain_sf, C2CD2/C2CD2L
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
SLC38A1	Other/Unknown	no		AA_transpt_TM
DMRTA1	Other/Unknown	no		DM_DNA-bd, DMA, UBA-like_sf
PRND	Other/Unknown	no		Doppel, Prion/Doppel_prot_b-ribbon_dom, Prion/Doppel_b-ribbon_dom_sf
TGM6	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
ZFPM2	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_FOG, Znf_C2H2_sf
TENT4A	Enzyme (other)	yes	2.7.7.19	PAP_assoc, NT_sf, Trf4-like
MFN2	Other/Unknown	no		Fzo/mitofusin_HR2, Mitofusin_fam, P-loop_NTPase
DPF3	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
DROSHA	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, RNase_III, dsRBD_dom
CNOT6L	Phosphatase	yes	3.1.13.4	Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, Endo/exonuclease/phosphatase
HCG23	Other/Unknown	no
CLCN6	Other/Unknown	no		CBS_dom, ClC, Cl_channel-6
SMOC1	Other/Unknown	no		Thyroglobulin_1, Kazal_dom, EF-hand-dom_pair
C6orf118	Other/Unknown	no		TSNAXIP1_N
VPS13C	Other/Unknown	no		VPS13_VAB, VPS13, VPS13_N
E2F7	Other/Unknown	no		E2F_WHTH_DNA-bd_dom, E2F, WH-like_DNA-bd_sf
CTAGE1	Other/Unknown	no		cTAGE_MIA/OTOR
GRAMD2B	Other/Unknown	no		GRAM, PH-like_dom_sf, GRAM_domain_protein_2B
CABLES1	Other/Unknown	no		Cyclin_N, CABLES1/2, Cyclin-like_sf
MIIP	Other/Unknown	no		MIIP
NAA60	Enzyme (other)	yes	2.3.1.259	GNAT_dom, Acyl_CoA_acyltransferase, NAA60-like
CYP2C8	Enzyme (other)	yes	1.14.14.1	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
CFAP54	Other/Unknown	no		CFAP54
LINC00955	Other/Unknown	no
LINC03122	Other/Unknown	no
PLD5	Other/Unknown	no		PLipase_D/transphosphatidylase, PLDc_3, Diverse_PLD-related
RNF187	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
ASAP1	Scaffold/PPI	no		ArfGAP_dom, SH3_domain, PH_domain
UBLCP1	Other/Unknown	no		Ubiquitin-like_dom, FCP1_dom, HAD-SF_hydro_IIID
DCUN1D5	Enzyme (other)	yes	2.3.2.32	PONY_dom, DCN-prot, DCN1-like_PONY
KIAA2013	Other/Unknown	no		K2013-like
VWA8	Other/Unknown	no		VWF_A, AAA+_ATPase, ATPase_dyneun-rel_AAA
DYNC2H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DSCAM	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SNORD114-31	Other/Unknown	no
MSANTD1	Other/Unknown	no		Myb/SANT-like_DNA-bd_dom_prot, Myb_DNA-bind_4
AGMO	Enzyme (other)	yes	1.14.16.5	Fatty_acid_hydroxylase, Sterol_desaturase/TMEM195, AGMP_C
ESRRB	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
NCS1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
GATA6	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA
GLO1	Enzyme (other)	yes	4.4.1.5	Glyas_Fos-R_dOase_dom, Glyoxalase_1, Glyoxalase_1_CS

Expression context

Cohort genes with no expression data: 1.

61 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)	2
broad (>20)	66
unknown	1

Top tissues across cohort

Tissue	Cohort genes
granulocyte	7
male germ line stem cell (sensu Vertebrata) in testis	7
ileal mucosa	5
jejunal mucosa	4
primordial germ cell in gonad	4
sural nerve	4
ventricular zone	4
germinal epithelium of ovary	4
right lobe of liver	4
oocyte	4
secondary oocyte	4
right atrium auricular region	4
right lung	3
cortical plate	3
ganglionic eminence	3
leukocyte	3
monocyte	3
left testis	3
right testis	3
apex of heart	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SALL2	243	ubiquitous	marker	cerebellar vermis, superior vestibular nucleus, paraflocculus
SLC6A4	162	tissue_specific	marker	right lung, jejunal mucosa, ileal mucosa
SOX11	93	broad	marker	ganglionic eminence, cortical plate, embryo
SPON1	272	broad	marker	gall bladder, mucosa of sigmoid colon, pericardium
BTNL2	106		yes	sural nerve, ventricular zone, primordial germ cell in gonad
TNFRSF1B	262	ubiquitous	marker	granulocyte, monocyte, leukocyte
TNFRSF8	148	broad	yes	granulocyte, monocyte, leukocyte
C2CD2	275	ubiquitous	marker	right adrenal gland cortex, adrenal cortex, left adrenal gland cortex
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
SLC38A1	282	ubiquitous	marker	lateral nuclear group of thalamus, seminal vesicle, superficial temporal artery
DMRTA1	131	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, islet of Langerhans
PRND	98	tissue_specific	marker	right testis, left testis, adult organism
TGM6	39	tissue_specific	marker	colonic epithelium, bone marrow cell, kidney epithelium
ZFPM2	239	ubiquitous	marker	skeletal muscle tissue of biceps brachii, germinal epithelium of ovary, biceps brachii
TENT4A	293	ubiquitous	marker	secondary oocyte, oocyte, tibia
MFN2	297	ubiquitous	marker	apex of heart, heart left ventricle, cardiac ventricle
DPF3	217	ubiquitous	marker	left ventricle myocardium, quadriceps femoris, vastus lateralis
DROSHA	283	ubiquitous	marker	endothelial cell, ventricular zone, germinal epithelium of ovary
CNOT6L	256	ubiquitous	marker	secondary oocyte, oocyte, ileal mucosa
HCG23
CLCN6	239	ubiquitous	marker	right testis, left testis, right atrium auricular region
SMOC1	203	broad	marker	ganglionic eminence, inferior vagus X ganglion, right lobe of liver
C6orf118	114	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, bronchial epithelial cell
VPS13C	291	ubiquitous	marker	calcaneal tendon, upper leg skin, epithelium of nasopharynx
E2F7	153	ubiquitous	yes	ventricular zone, thymus, upper arm skin
CTAGE1	13	tissue_specific	yes	right testis, left testis, testis
GRAMD2B	282	ubiquitous	marker	calcaneal tendon, medial globus pallidus, globus pallidus
CABLES1	218	ubiquitous	marker	putamen, caudate nucleus, nucleus accumbens
MIIP	288	ubiquitous	marker	granulocyte, type B pancreatic cell, vena cava
NAA60	288	ubiquitous	marker	pancreatic ductal cell, endothelial cell, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 21.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL6	9,239
DROSHA	6,846
WT1	3,938
MFN2	3,853
MTHFR	3,492
HLA-DRB1	3,448
HLA-DRA	3,244
RBBP8	3,235
TNFRSF1B	2,885
DSCAM	2,848

Intra-cohort edges

A	B	Sources
BTNL2	HLA-DQB1	intact
BTNL2	HLA-DRA	string_interaction
BTNL2	HLA-DRB1	string_interaction
BTNL2	HLA-DRB5	string_interaction
CABLES1	CTAGE1	string_interaction
CLCN6	MTHFR	string_interaction
DPF3	IL6	intact
DSCAM	TNFRSF8	intact
ESRRB	IL12B	intact
ESRRB	PCSK6	string_interaction
HLA-DRA	HLA-DRB1	biogrid_interaction, intact, string_interaction
HLA-DRA	HLA-DRB5	biogrid_interaction, intact, string_interaction
HLA-DRB1	HLA-DRB5	biogrid_interaction, intact
IL12B	IL6	string_interaction
IL6	TNFRSF1B	string_interaction
KIAA2013	MIIP	string_interaction
KIAA2013	PLOD1	string_interaction
MIIP	PLOD1	string_interaction
NPPA	NPPB	string_interaction
SOX11	WT1	string_interaction
TNFRSF1B	TNFRSF8	string_interaction

Structural data

PDB: 36 · AlphaFold-only: 27 · No structure: 6

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRA	P01903	140
HLA-DRB1	P01911	108
SLC6A4	P31645	30
WT1	P19544	28
IL12B	P29460	20
IL6	P05231	17
GLO1	Q04760	16
NCS1	P62166	14
NPPA	P01160	13
DROSHA	Q9NRR4	12
HLA-DQB1	P01920	10
LRPAP1	P30533	10
DPF3	Q92784	8
CNOT6L	Q96LI5	8
IL2RB	P14784	8
TNFRSF1B	P20333	5
NAA60	Q9H7X0	5
CYP2C8	P10632	5
ASAP1	Q9ULH1	5
SOX11	P35716	4
SPON1	Q9HCB6	4
DYNC2H1	Q8NCM8	4
HLA-DRB5	Q30154	4
MTHFR	P42898	4
RBBP8	Q99708	4
MFN2	O95140	3
CLCN6	P51797	3
UBLCP1	Q8WVY7	3
ESRRB	O95718	3
ASNS	P08243	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGMO	Q6ZNB7	93.90
PLOD1	Q02809	93.04
TGM6	O95932	90.95
DCUN1D5	Q9BTE7	88.05
BTNL2	Q9UIR0	85.97
KIAA2013	Q8IYS2	85.77
PLD5	Q8N7P1	83.26
PCSK6	P29122	81.84
SLC38A1	Q9H2H9	79.81
VWA8	A3KMH1	79.24
SMOC1	Q9H4F8	73.69
MSANTD1	Q6ZTZ1	72.75
C6orf118	Q5T5N4	70.77
CTAGE1	Q96RT6	70.45
GRAMD2B	Q96HH9	63.97
TENT4A	Q5XG87	62.58
C2CD2	Q9Y426	62.52
CABLES1	Q8TDN4	57.66
MIIP	Q5JXC2	57.42
DMRTA1	Q5VZB9	57.14
GATA6	Q92908	53.48
SALL2	Q9Y467	52.09
ZFPM2	Q8WW38	51.93
E2F7	Q96AV8	51.31
LINC03122	Q2M2E5	51.09
VPS13C	Q709C8
CFAP54	Q96N23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 157. Enrichment computed across 69 evidence-associated genes (40 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 40 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Translocation of ZAP-70 to Immunological synapse	3	47.6×	0.003	HLA-DRA, HLA-DRB1, HLA-DRB5
Phosphorylation of CD3 and TCR zeta chains	3	40.8×	0.003	HLA-DRA, HLA-DRB1, HLA-DRB5
Co-inhibition by PD-1	3	38.9×	0.003	HLA-DRA, HLA-DRB1, HLA-DRB5
Generation of second messenger molecules	3	25.9×	0.008	HLA-DRA, HLA-DRB1, HLA-DRB5
Interferon gamma signaling	4	12.6×	0.009	HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
Interleukin-10 signaling	3	17.5×	0.017	TNFRSF1B, IL12B, IL6
Transcriptional regulation of testis differentiation	2	35.7×	0.031	WT1, ZFPM2
Factors involved in megakaryocyte development and platelet production	4	6.6×	0.058	ZFPM2, MFN2, CABLES1, GATA6
Downstream TCR signaling	3	9.6×	0.064	HLA-DRA, HLA-DRB1, HLA-DRB5
TNFs bind their physiological receptors	2	19.7×	0.072	TNFRSF1B, TNFRSF8
Interleukin-4 and Interleukin-13 signaling	3	7.7×	0.097	TNFRSF1B, IL12B, IL6
Neurotransmitter uptake and metabolism In glial cells	1	95.2×	0.126	SLC38A1
MHC class II antigen presentation	3	6.7×	0.126	HLA-DRA, HLA-DRB1, HLA-DRB5
NGF processing	1	71.4×	0.146	PCSK6
Serotonin clearance from the synaptic cleft	1	71.4×	0.146	SLC6A4
DSCAM interactions	1	57.1×	0.161	DSCAM
Miro GTPase Cycle	1	57.1×	0.161	MFN2
Astrocytic Glutamate-Glutamine Uptake And Metabolism	1	47.6×	0.172	SLC38A1
Biosynthesis of maresin-like SPMs	1	47.6×	0.172	CYP2C8
Signaling by BRAF and RAF1 fusions	2	8.5×	0.180	TENT4A, CLCN6
RHOT2 GTPase cycle	1	40.8×	0.181	MFN2
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	35.7×	0.189	CYP2C8
Neurotransmitter clearance	1	31.7×	0.189	SLC6A4
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	31.7×	0.189	CYP2C8
Interleukin-23 signaling	1	31.7×	0.189	IL12B
MAPK1 (ERK2) activation	1	28.6×	0.189	IL6
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	1	28.6×	0.189	GATA6
CD163 mediating an anti-inflammatory response	1	28.6×	0.189	IL6
MAPK3 (ERK1) activation	1	25.9×	0.189	IL6
Mitophagy	1	25.9×	0.189	MFN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 55 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	4	76.6×	1e-04	HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
positive regulation of memory T cell differentiation	3	102.1×	6e-04	HLA-DRA, HLA-DRB1, IL12B
antigen processing and presentation of exogenous peptide antigen via MHC class II	4	39.5×	6e-04	HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
positive regulation of immune response	4	35.0×	7e-04	HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
positive regulation of T cell activation	4	32.2×	8e-04	HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
antigen processing and presentation of endogenous peptide antigen via MHC class II	2	306.4×	0.001	HLA-DRA, HLA-DRB1
myeloid dendritic cell antigen processing and presentation	2	204.3×	0.003	HLA-DRA, HLA-DRB1
regulation of T-helper cell differentiation	2	153.2×	0.004	HLA-DRA, HLA-DRB1
negative regulation of female gonad development	2	153.2×	0.004	WT1, ZFPM2
positive regulation of CD4-positive, alpha-beta T cell activation	2	153.2×	0.004	HLA-DRA, HLA-DRB1
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	2	122.6×	0.006	HLA-DRA, HLA-DRB1
cellular response to gonadotropin stimulus	2	102.1×	0.008	WT1, GATA6
positive regulation of T cell mediated cytotoxicity	3	27.9×	0.008	HLA-DRA, HLA-DRB1, IL12B
male mating behavior	2	76.6×	0.012	SLC6A4, DMRTA1
T-helper 1 type immune response	2	68.1×	0.015	HLA-DRB1, IL12B
positive regulation of male gonad development	2	61.3×	0.017	WT1, ZFPM2
cGMP biosynthetic process	2	51.1×	0.022	NPPA, NPPB
regulation of neuroinflammatory response	2	51.1×	0.022	TNFRSF1B, IL6
receptor guanylyl cyclase signaling pathway	2	47.1×	0.025	NPPA, NPPB
humoral immune response	3	15.3×	0.029	HLA-DQB1, HLA-DRB1, IL6
negative regulation of systemic arterial blood pressure	2	38.3×	0.031	NPPA, NPPB
cardiac conduction system development	2	38.3×	0.031	NPPA, NPPB
cardiac muscle hypertrophy in response to stress	2	38.3×	0.031	GATA6, NPPA
positive regulation of T cell proliferation	3	14.1×	0.031	BTNL2, IL12B, IL6
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	306.4×	0.046	HLA-DRA
N-terminal peptidyl-methionine acetylation	1	306.4×	0.046	NAA60
regulation of interleukin-4 production	1	306.4×	0.046	HLA-DRB1
negative regulation of transforming growth factor beta2 production	1	306.4×	0.046	GATA6
tube morphogenesis	1	306.4×	0.046	GATA6
regulation of receptor-mediated endocytosis	1	306.4×	0.046	LRPAP1

Therapeutics

Drugs indicated for this disease

15 approved, 28 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aminosalicylic Acid	Approved (phase 4)
Bedaquiline	Approved (phase 4)
Capreomycin	Approved (phase 4)
Cycloserine	Approved (phase 4)
Delamanid	Approved (phase 4)
Ethambutol	Approved (phase 4)
Ethionamide	Approved (phase 4)
Isoniazid	Approved (phase 4)
Pretomanid	Approved (phase 4)
Protionamide	Approved (phase 4)
Pyrazinamide	Approved (phase 4)
Rifabutin	Approved (phase 4)
Rifampin	Approved (phase 4)
Rifamycin	Approved (phase 4)
Rifapentine	Approved (phase 4)
Abacavir	Phase 3 (in late-stage trials)
Bcg Vaccine	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Clarithromycin	Phase 3 (in late-stage trials)
Clofazimine	Phase 3 (in late-stage trials)
Didanosine	Phase 3 (in late-stage trials)
Efavirenz	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
Gatifloxacin	Phase 3 (in late-stage trials)
Kanamycin	Phase 3 (in late-stage trials)
Lactose, Anhydrous	Phase 3 (in late-stage trials)
Lamivudine	Phase 3 (in late-stage trials)
Linezolid	Phase 3 (in late-stage trials)
Meloxicam	Phase 3 (in late-stage trials)
Moxifloxacin	Phase 3 (in late-stage trials)
Nevirapine	Phase 3 (in late-stage trials)
Niacin	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Pyridoxine	Phase 3 (in late-stage trials)
Retinol	Phase 3 (in late-stage trials)
Sitafloxacin Anhydrous	Phase 3 (in late-stage trials)
Sudapyridine	Phase 3 (in late-stage trials)
Sulfamethoxazole	Phase 3 (in late-stage trials)
Trimethoprim	Phase 3 (in late-stage trials)
Tuberculin	Phase 3 (in late-stage trials)
Zidovudine	Phase 3 (in late-stage trials)
Zinc Ion	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine, Amikacin, Amoxicillin, Aspirin, Atorvastatin, Auranofin, Azithromycin, Clavulanic Acid, Co-Trimoxazole, Dexamethasone, Ertapenem, Everolimus, Ibuprofen, Imatinib, Meropenem, Metronidazole, Nitazoxanide, Pravastatin, Sodium Chloride.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 7 · Undrugged: 62

Druggability breadth: 29 of 69 evidence-associated genes (42%) 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
CYP2C8	CLOTRIMAZOLE
ESRRB	ESTRADIOL
GLO1	TOLMETIN
IL6	PREDNISOLONE
RGS12	PSEUDOEPHEDRINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A4	422	4
CYP2C8	62	4
GLO1	11	4
RGS12	8	4
IL6	3	4
ESRRB	2	4
NPPA	1	2
SALL2	0	0
SOX11	0	0
SPON1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	SLC6A4
CLOTRIMAZOLE	4	CYP2C8, SLC6A4
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	SLC6A4
DESLORATADINE	4	SLC6A4
DULOXETINE	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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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

Symbol	Assays	Type breakdown
SLC6A4	1,055	Binding:1021, Functional:18, ADMET:9, Toxicity:6, Unclassified:1
CYP2C8	1,025	ADMET:1005, Binding:19, Toxicity:1
GLO1	72	Binding:70, ADMET:1, Functional:1
ESRRB	27	Binding:19, Functional:8
ASNS	27	Binding:27
HLA-DRB1	17	Binding:17
IL6	16	Binding:16
DCUN1D5	11	Binding:11
PCSK6	9	Binding:9
TGM6	8	Binding:8
TNFRSF1B	6	Binding:6
UBLCP1	5	Binding:5
NPPA	5	Binding:5
TENT4A	4	Binding:4
MFN2	3	Binding:3
SLC38A1	2	Binding:2
NCS1	2	Binding:2
RGS12	2	Functional:2
CNOT6L	1	Binding:1
CABLES1	1	Binding:1
NAA60	1	Binding:1
ASAP1	1	Functional:1
IL2RB	1	Binding:1
PLOD1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TGM6	2.3.2.13	protein-glutamine gamma-glutamyltransferase
TENT4A	2.7.7.19	polynucleotide adenylyltransferase
DROSHA	3.1.26.3	ribonuclease III
CNOT6L	3.1.13.4	poly(A)-specific ribonuclease
NAA60	2.3.1.259	N-terminal methionine Nalpha-acetyltransferase NatF
CYP2C8	1.14.14.1	unspecific monooxygenase
DCUN1D5	2.3.2.32	cullin-RING-type E3 NEDD8 transferase
AGMO	1.14.16.5	alkylglycerol monooxygenase
GLO1	4.4.1.5	lactoylglutathione lyase
MTHFR	1.5.1.20, 1.5.1.53	methylenetetrahydrofolate reductase [NAD(P)H], methylenetetrahydrofolate reductase (NADPH)
ASNS	6.3.5.4	asparagine synthase (glutamine-hydrolysing)
PCSK6	3.4.21.61, 3.4.21.B25	Kexin,

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
CYP2C8	1,025

Pharmacogenomics

Cohort genes with a PharmGKB record: 66; with CPIC/DPWG dosing guidelines: 2.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
SLC6A4	1
CYP2C8	1

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	SLC6A4
CLOTRIMAZOLE	4	CYP2C8, SLC6A4
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	SLC6A4
DESLORATADINE	4	SLC6A4
DULOXETINE	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)	6	SLC6A4, CYP2C8, ESRRB, GLO1, IL6, RGS12
B	Phased (≥1) drug, not yet approved	1	NPPA
C	Druggable family + PDB, no drug	12	DROSHA, CNOT6L, NAA60, DSCAM, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, IL12B, IL2RB (+2 more)
D	Druggable family + AlphaFold only, no drug	6	BTNL2, TGM6, TENT4A, DCUN1D5, AGMO, PCSK6
E	Difficult family or no structure, no drug	44	SALL2, SOX11, SPON1, TNFRSF1B, TNFRSF8, C2CD2, WT1, SLC38A1, DMRTA1, PRND (+34 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NPPB	0	NPPA
PCSK6	9	ESRRB
SALL2	0	—
SOX11	0	—
SPON1	0	—
BTNL2	0	—
TNFRSF1B	6	—
TNFRSF8	0	—
C2CD2	0	—
WT1	0	—
SLC38A1	2	—
DMRTA1	0	—
PRND	0	—
TGM6	8	—
ZFPM2	0	—
TENT4A	4	—
MFN2	3	—
DPF3	0	—
DROSHA	0	—
CNOT6L	1	—
HCG23	0	—
CLCN6	0	—
SMOC1	0	—
C6orf118	0	—
VPS13C	0	—
E2F7	0	—
CTAGE1	0	—
GRAMD2B	0	—
CABLES1	1	—
MIIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 952.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	534
PHASE1	139
PHASE2	110
PHASE3	72
PHASE4	55
PHASE2/PHASE3	19
PHASE1/PHASE2	18
EARLY_PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05118490	PHASE4	ACTIVE_NOT_RECRUITING	Comparing Treatment Completion Of Daily Rifapentine & Isoniazid For One Month (1HP) To Weekly High Dose Rifapentine & Isoniazid For 3 Months (3HP) In Persons Living With HIV and in Household Contacts of Recently Diagnosed Tuberculosis Patients
NCT06153069	PHASE4	RECRUITING	Asymptomatic TB With Innovative Modified Short-course Regimens
NCT06403943	PHASE4	RECRUITING	Efficacy Safety BaiDiZiYin ShenQiYiFei Adjunctive Treatments Pulmonary Tuberculosis
NCT06484530	PHASE4	RECRUITING	Gene-guided N-acetyl Cysteine for Prophylaxis of Anti-tuberculous Drug- Induced Hepatitis
NCT00023400	PHASE4	COMPLETED	TBTC Study 23B:Intensive PK of the Nelfinavir Rifabutin Interaction in Patients With HIV-TB
NCT00107887	PHASE4	COMPLETED	TB (Tuberculosis) Preventive Therapy for HIV Patients With Access to HAART (Highly Active Antiretroviral Therapy)
NCT00108862	PHASE4	COMPLETED	Immediate Versus Deferred Start of Anti-HIV Therapy in HIV-Infected Adults Being Treated for Tuberculosis
NCT00146302	PHASE4	COMPLETED	Should Low Birth Weight Infants Be Vaccinated With BCG Vaccine at Birth in Developing Countries?
NCT00164281	PHASE4	COMPLETED	Study of Limited Versus Continuous Isoniazid Tuberculosis Preventive Therapy in HIV-infected Persons in Botswana
NCT00216333	PHASE4	UNKNOWN	Multicenter Trial for the Evaluation of a Fixed Dose Combined Tablet for the Treatment of Pulmonary Tuberculosis
NCT00242047	PHASE4	UNKNOWN	Randomized Controlled Trial of Percutaneous and Intradermal BCG Vaccination.
NCT00293228	PHASE4	COMPLETED	Treatment of Latent Tuberculosis Infection With Isoniazid
NCT00311220	PHASE4	UNKNOWN	Use TST and QFT-RD1 Test to Monitor the Tuberculous Infection in Patients, Close Contact People and Health Care Workers
NCT00397709	PHASE4	TERMINATED	Short-Course Isoniazid and Rifampin Compared With Isoniazid for Latent Tuberculosis Infection
NCT00402402	PHASE4	COMPLETED	Comparison of Quantiferon-TB Gold Assay With Tuberculin Skin Testing in Patients With Chronic Liver Disease
NCT00402610	PHASE4	COMPLETED	A Randomized Trial of Three Regimens to Prevent Tuberculosis in HIV-Infected Patients With Anergy
NCT00405301	PHASE4	COMPLETED	Study of Safety and Efficacy of Different Regimes of Reintroduction of Anti-TB Drugs in Anti-TB Drugs Induced Liver Damage
NCT00412009	PHASE4	COMPLETED	Investigation of a Novel Approach to Improve Treatment Success Rates for Tuberculosis Patients in Senegal
NCT00523458	PHASE4	TERMINATED	A Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV
NCT00533390	PHASE4	TERMINATED	Randomized Clinical Trial to Assess the Efficacy and Safety of Concomitant Use of Rifampicin and Efavirenz 600 X 800mg
NCT00617643	PHASE4	COMPLETED	Nevirapine Drug Levels in HIV Positive Patients Also Receiving Rifampicin for Tuberculosis
NCT00620438	PHASE4	UNKNOWN	Drug Interaction Between Coartem® and Nevirapine, Efavirenz or Rifampicin in HIV Positive Ugandan Patients
NCT00647205	PHASE4	COMPLETED	Evaluation of 2 Interferon γ Assays in the Diagnosis of Latent Tuberculosis in HIV-infected Patients.ANRS EP 40 QUANTI SPOT
NCT00728546	PHASE4	UNKNOWN	NAT2 in Re-challenge of INH in Patients With Hepatitis
NCT00771498	PHASE4	COMPLETED	An Evaluation of the Pharmacological Interaction of Lopinavir/r and Rifampin
NCT00797836	PHASE4	COMPLETED	Quantiferon for Detection of Latent Tuberculosis in Healthcare Workers
NCT00850915	PHASE4	COMPLETED	Feasibility and Effectiveness of Community Based Isoniazid Preventive Therapy in Kenya
NCT00851630	PHASE4	COMPLETED	Tuberculosis and Human Immunodeficiency Virus (HIV) Immune Reconstitution Syndrome Trial (THIRST)
NCT01014481	PHASE4	TERMINATED	Appropriate Timing of HAART in Co-infected HIV/TB Patients
NCT01048697	PHASE4	COMPLETED	Effect of Weight and/or Obesity on Ethambutol Drug Concentrations
NCT01059422	PHASE4	COMPLETED	Raltegravir + Lamivudine/Abacavir in HIV/Tuberculosis Co-Infected Patients
NCT01165840	PHASE4	COMPLETED	Effect of Weight and/or Obesity on Dapsone Drug Concentrations
NCT01167452	PHASE4	COMPLETED	Effect of Weight and/or Obesity on Sulfamethoxazole and Trimethoprim Concentrations
NCT01223976	PHASE4	UNKNOWN	Sensitivity and Specificity of QuantiFeron -TB Gold Test (QFT-G)in Patients With Psoriasis
NCT01329250	PHASE4	TERMINATED	Pharmacokinetics and Safety of Moxifloxacin
NCT01363765	PHASE4	COMPLETED	Xpert MTB/Rif, a New Tool for the Diagnosis of Pulmonary Tuberculosis in Two Municipalities in Brazil
NCT01417988	PHASE4	TERMINATED	Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment
NCT01494038	PHASE4	COMPLETED	Evaluating the Safety of Immediate Versus Deferred Isoniazid Preventive Therapy Among HIV-Infected Pregnant Women
NCT01637558	PHASE4	COMPLETED	Optimal Dosing of 1st Line Antituberculosis and Antiretroviral Drugs in Children (a Pharmacokinetic Study)
NCT01700790	PHASE4	TERMINATED	Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ISONIAZID	4	63
PYRIDOXINE	4	34
PYRAZINAMIDE	4	29
ETHAMBUTOL	4	26
RIFAPENTINE	4	23
BEDAQUILINE	4	22
RIFAMPIN	4	22
PRETOMANID	4	14
RIFABUTIN	4	14
MOXIFLOXACIN	4	13
LINEZOLID	4	7
DOLUTEGRAVIR	4	6
EFAVIRENZ	4	6
DELAMANID	4	5
ABACAVIR	4	4
CLOFAZIMINE	4	4
LEVOFLOXACIN ANHYDROUS	4	4
LOPINAVIR	4	4
NEVIRAPINE	4	4
RALTEGRAVIR	4	4
DEXAMETHASONE	4	3
ENTECAVIR ANHYDROUS	4	3
LAMIVUDINE	4	3
ETHIONAMIDE	4	2
KANAMYCIN	4	2
RITONAVIR	4	2
TRIMETHOPRIM	4	2
AURANOFIN	4	1
DAPSONE	4	1
DIDANOSINE	4	1