Malaria

Summary

Malaria (MONDO:0005136) is a disease (an umbrella term covering 7 Mondo subtypes) with 75 cohort genes (158 GWAS associations across 14 studies) and 889 clinical trials. The dominant Reactome pathway is Expression and translocation of olfactory receptors (59 cohort genes). Top therapeutic interventions include amodiaquine, primaquine, and chloroquine.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 158
• Phenotypes (HPO): 16
• Clinical trials: 889

Clinical features

Epidemiology

Prevalence records

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

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	1.2	Europe	Validated
Point prevalence	1-9 / 100 000	3	Europe	Validated
Annual incidence	1-9 / 100 000	1.62	Denmark	Validated
Annual incidence	1-9 / 1 000 000	0.75	Iceland	Validated
Annual incidence	1-9 / 1 000 000	0.8	Austria	Validated
Annual incidence	1-9 / 100 000	2.1	Belgium	Validated
Annual incidence	1-9 / 1 000 000	0.16	Bulgaria	Validated
Annual incidence	1-9 / 1 000 000	0.1	Croatia	Validated
Annual incidence	1-9 / 1 000 000	0.52	Cyprus	Validated
Annual incidence	1-9 / 1 000 000	0.32	Czech Republic	Validated
Annual incidence	1-9 / 1 000 000	0.2	Estonia	Validated
Annual incidence	1-9 / 1 000 000	0.74	Finland	Validated
Annual incidence	1-9 / 1 000 000	0.68	Greece	Validated
Annual incidence	1-9 / 1 000 000	0.14	Hungary	Validated
Annual incidence	1-9 / 100 000	1.7	Ireland	Validated
Annual incidence	1-9 / 1 000 000	0.18	Latvia	Validated
Annual incidence	1-9 / 1 000 000	0.22	Lithuania	Validated
Annual incidence	1-9 / 1 000 000	0.84	Luxembourg	Validated
Annual incidence	1-9 / 100 000	1.54	Malta	Validated
Annual incidence	1-9 / 100 000	1.84	Netherlands	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0001903	Anemia	Very frequent (80-99%)
HP:0001919	Acute kidney injury	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002011	Morphological central nervous system abnormality	Very frequent (80-99%)
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0002315	Headache	Very frequent (80-99%)
HP:0011227	Elevated circulating C-reactive protein concentration	Very frequent (80-99%)
HP:0001871	Abnormality of blood and blood-forming tissues	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)
HP:0002141	Gait imbalance	Frequent (30-79%)
HP:0002904	Hyperbilirubinemia	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0004372	Reduced consciousness/confusion	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0000488	Retinopathy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	malaria
Mondo ID	MONDO:0005136
EFO	EFO:0001068
MeSH	D008288
Orphanet	673
DOID	DOID:12365
ICD-10-CM	B53
ICD-11	1439886552
NCIT	C34797
SNOMED CT	61462000
UMLS	C0024530
MedGen	7443
GARD	0006961
MedDRA	10025487
NORD	1395
Is cancer (heuristic)	no

Data availability: 158 GWAS associations (14 studies).

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › parasitic infectious disease › protozoa infectious disease › malaria

Related subtypes (14): primary amebic meningoencephalitis, granulomatous amebic encephalitis, trypanosomiasis, giardiasis, protozoal dysentery, trichomoniasis, Acanthamoeba keratitis, amebiasis, babesiosis, balantidiasis, coccidiosis, theileriasis, leishmaniasis, dientamoebiasis

Subtypes (7): Plasmodium ovale malaria, Plasmodium malariae malaria, mixed malaria, cerebral malaria, blackwater fever, Plasmodium falciparum malaria, Plasmodium vivax malaria

Genetics & variants

GWAS landscape

158 GWAS associations across 14 studies. Top hits map to 38 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs334	4e-69	HBB	?	1.57
rs8176719	4e-21	ABO	G	1.48
rs12788102	2e-16	OR51F1, MMP26	A	2.15
rs372091	6e-14	HBG2, OR51B5, HBE1	C	2.17
rs4951377	1e-11	ATP2B4	?	0.4
rs11036238	4e-11	OR51V1 - HBB	?	1.59
rs186873296	4e-11	GUSBP5	?
rs567544458	7e-11	FREM3, GUSBP5	?	0.59
rs10900585	2e-10	ATP2B4	T	1.64
rs8176722	9e-10	ABO	A	1.28
rs80169640	2e-09	CHST15 - OAT	A	0.41
rs116423146	3e-09	ARL14 - SNORA72	?	0.28
rs57032711	1e-08	MVB12B	?	0.23
rs142480106	5e-08	MYLK4	T	2.52
rs1469170	8e-08	HNRNPA1P60 - RNA5SP350	A	1.2
rs74806154	8e-08	DIP2C	?	0.14
rs9296359	1e-07	TREML4	?	4.09
rs113449872	2e-07	NNT - RNU6-381P	?	2.82
rs149085856	2e-07	MAP2K4 - LINC00670	?	3.87
rs199722126	2e-07	STAU2	?	0.21
rs116782507	2e-07	RNU6-649P - LINC01248	?	0.38
rs11335470	3e-07	LINC00944	?	2.48
rs5784724	3e-07	SMPDL3A	?	0.21
rs56291704	3e-07	LINC01320	?	0.17
rs73832816	4e-07	ADH7 - C4orf17	?	3.46
rs76088706	4e-07	LINC01600	T	2.22
rs6124419	4e-07	PTPRT	A	1.58
rs6117276	4e-07	CASC20	?	0.46
rs12083051	4e-07	SMYD3	?	0.14
rs7701116	4e-07	SIL1	?	0.17

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010725	Malaria Genomic Epidemiology Network	2019	7,957	7,746	Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania.
GCST002033	Band G	2013	5,425	6,891	Imputation-based meta-analysis of severe malaria in three African populations.
GCST003145	Band G	2015	5,130	5,291	A novel locus of resistance to severe malaria in a region of ancient balancing selection.
GCST000410	Jallow M	2009	958	1,382	Genome-wide and fine-resolution association analysis of malaria in West Africa.
GCST90473091	UK Biobank Whole-Genome Sequencing Consortium	2025	744	457,696	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90077848	Backman JD	2021	563	331,191	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081834	Backman JD	2021	563	331,191	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST005356	Ravenhall M	2018	449	0	Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania.
GCST005357	Ravenhall M	2018	449	0	Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania.
GCST90297839	Hamid I	2024	46	0	Mid-pass Whole-genome Sequencing in a Malagasy Cohort Uncovers Body Composition Associations.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	38
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	9

Functional consequences

Consequence	Count
intron_variant	30
intergenic_variant	14
3_prime_UTR_variant	2
missense_variant	1
frameshift_variant	1
synonymous_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs334	11	5227002	T>A,C,G		missense_variant	HBB	4e-69	Tier 1: coding
rs8176719	9	133257522	T>TC	0.37	frameshift_variant	ABO	4e-21	Tier 1: coding
rs12788102	11	4769345	A>G	0.05	synonymous_variant	OR51F1, MMP26	2e-16	Tier 4: intronic/intergenic
rs372091	11	5496926	A>C,G,T	0.028	intron_variant	HBG2, OR51B5, HBE1	6e-14	Tier 4: intronic/intergenic
rs4951377	1	203689343	A>G	0.05	intron_variant	ATP2B4	1e-11	Tier 4: intronic/intergenic
rs11036238	11	5204405	G>C	0.14	intergenic_variant	OR51V1 - HBB	4e-11	Tier 4: intronic/intergenic
rs186873296	4	143781321	A>G		intron_variant	GUSBP5	4e-11	Tier 4: intronic/intergenic
rs567544458	4	143592208	T>G		intron_variant	FREM3, GUSBP5	7e-11	Tier 4: intronic/intergenic
rs10900585	1	203684896	G>A,C,T	0.38	intron_variant	ATP2B4	2e-10	Tier 4: intronic/intergenic
rs8176722	9	133257367	C>A	0.05	intron_variant	ABO	9e-10	Tier 4: intronic/intergenic
rs80169640	10	124100463	G>A	0.17	intergenic_variant	CHST15 - OAT	2e-09	Tier 4: intronic/intergenic
rs116423146	3	160679075	C>T	0.05	intergenic_variant	ARL14 - SNORA72	3e-09	Tier 4: intronic/intergenic
rs57032711	9	126487840	G>A	0.05	intron_variant	MVB12B	1e-08	Tier 4: intronic/intergenic
rs142480106	6	2666821	C>A,G,T	0.019	3_prime_UTR_variant	MYLK4	5e-08	Tier 2: splice/UTR
rs1469170	11	110870290	A>G	0.05	intergenic_variant	HNRNPA1P60 - RNA5SP350	8e-08	Tier 4: intronic/intergenic
rs74806154	10	574544	G>GGCAC	0.05	intron_variant	DIP2C	8e-08	Tier 4: intronic/intergenic
rs9296359	6	41237952	G>A,T	0.05	3_prime_UTR_variant	TREML4	1e-07	Tier 2: splice/UTR
rs113449872	5	43909241	G>A,T	0.05	intergenic_variant	NNT - RNU6-381P	2e-07	Tier 4: intronic/intergenic
rs149085856	17	12496210	GC>G,GCC,GCCC		intergenic_variant	MAP2K4 - LINC00670	2e-07	Tier 4: intronic/intergenic
rs199722126	8	73585144	T>TTAAA	0.05	intron_variant	STAU2	2e-07	Tier 4: intronic/intergenic
rs116782507	2	5295571	A>C,G		intergenic_variant	RNU6-649P - LINC01248	2e-07	Tier 4: intronic/intergenic
rs11335470	12	126753075	GT>G	0.05	intron_variant	LINC00944	3e-07	Tier 4: intronic/intergenic
rs5784724	6	122807710	CT>C,CTT,CTTT	0.05	intron_variant	SMPDL3A	3e-07	Tier 4: intronic/intergenic
rs56291704	2	33976154	G>A,C,T	0.05	intron_variant	LINC01320	3e-07	Tier 4: intronic/intergenic
rs73832816	4	99508600	G>A	0.05	intergenic_variant	ADH7 - C4orf17	4e-07	Tier 4: intronic/intergenic
rs76088706	6	2606805	G>T	0.025	intron_variant	LINC01600	4e-07	Tier 4: intronic/intergenic
rs6124419	20	42134228	G>A	0.12	intron_variant	PTPRT	4e-07	Tier 4: intronic/intergenic
rs6117276	20	6467874	C>T	0.05	intergenic_variant	CASC20	4e-07	Tier 4: intronic/intergenic
rs12083051	1	245838142	G>T	0.05	intron_variant	SMYD3	4e-07	Tier 4: intronic/intergenic
rs7701116	5	139070389	C>T	0.05	intron_variant	SIL1	4e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RRM1	Orphanet:254886	Autosomal recessive progressive external ophthalmoplegia
SCO1	Orphanet:1561	Fatal infantile cytochrome C oxidase deficiency
SLC67A1	Orphanet:227535	Hereditary breast cancer
SLC67A1	Orphanet:99757	Embryonal rhabdomyosarcoma
SMARCA5	Orphanet:370334	Extraskeletal Ewing sarcoma
SMPD1	Orphanet:77292	Infantile neurovisceral acid sphingomyelinase deficiency
SMPD1	Orphanet:77293	Chronic visceral acid sphingomyelinase deficiency
STIM1	Orphanet:2593	Tubular aggregate myopathy
STIM1	Orphanet:317430	Combined immunodeficiency due to STIM1 deficiency
STIM1	Orphanet:3204	Stormorken-Sjaastad-Langslet syndrome
STX1A	Orphanet:586	Cystic fibrosis
STX1A	Orphanet:904	Williams syndrome
SURF1	Orphanet:391351	SURF1-related Charcot-Marie-Tooth disease type 4
TBL2	Orphanet:904	Williams syndrome
TNFAIP3	Orphanet:536	Systemic lupus erythematosus
TNFAIP3	Orphanet:674762	Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
MYOT	Orphanet:268129	Spheroid body myopathy
MYOT	Orphanet:98911	Distal myotilinopathy
TUB	Orphanet:791	Retinitis pigmentosa
ADAMTS13	Orphanet:93583	Congenital thrombotic thrombocytopenic purpura
DCHS1	Orphanet:314679	Cerebrofacioarticular syndrome
DCHS1	Orphanet:741	Familial mitral valve prolapse
ABHD16A	Orphanet:631085	Autosomal recessive spastic paraplegia type 86

Cohort genes → proteins

75 cohort genes, 68 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BCL7B	HGNC:1005	ENSG00000106635	Q9BQE9	B-cell CLL/lymphoma 7 protein family member B	gwas
TRIM34	HGNC:10063	ENSG00000258659	Q9BYJ4	E3 ubiquitin-protein ligase TRIM34	gwas
TRIM3	HGNC:10064	ENSG00000110171	O75382	Tripartite motif-containing protein 3	gwas
SNORD24	HGNC:10146	ENSG00000206611		small nucleolar RNA, C/D box 24	gwas
SNORD36A	HGNC:10163	ENSG00000199744		small nucleolar RNA, C/D box 36A	gwas
SNORD36B	HGNC:10164	ENSG00000200831		small nucleolar RNA, C/D box 36B	gwas
SNORD36C	HGNC:10165	ENSG00000252542		small nucleolar RNA, C/D box 36C	gwas
RPL7A	HGNC:10364	ENSG00000148303	P62424	Large ribosomal subunit protein eL8	gwas
RRM1	HGNC:10451	ENSG00000167325	P23921	Ribonucleoside-diphosphate reductase large subunit	gwas
RYR3	HGNC:10485	ENSG00000198838	Q15413	Ryanodine receptor 3	gwas
SCO1	HGNC:10603	ENSG00000133028	O75880	Cytochrome c oxidase assembly factor SCO1	gwas
SDC4	HGNC:10661	ENSG00000124145	P31431	Syndecan-4	gwas
SEMG1	HGNC:10742	ENSG00000124233	P04279	Semenogelin-1	gwas
SEMG2	HGNC:10743	ENSG00000124157	Q02383	Semenogelin-2	gwas
SF3B3	HGNC:10770	ENSG00000189091	Q15393	Splicing factor 3B subunit 3	gwas
ST3GAL2	HGNC:10863	ENSG00000157350	Q16842	CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 2	gwas
SLC67A1	HGNC:10964	ENSG00000110628	Q96BI1	Solute carrier family 67 member A1	gwas
SLC67A1-AS	HGNC:10965	ENSG00000254827	Q8N1D0	Uncharacterized protein SLC67A1-AS	gwas
SLPI	HGNC:11092	ENSG00000124107	P03973	Antileukoproteinase	gwas
SMARCA5	HGNC:11101	ENSG00000153147	O60264	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5	gwas
SMPD1	HGNC:11120	ENSG00000166311	P17405	Sphingomyelin phosphodiesterase	gwas
SPINT1	HGNC:11246	ENSG00000166145	O43278	Kunitz-type protease inhibitor 1	gwas
TRIM21	HGNC:11312	ENSG00000132109	P19474	E3 ubiquitin-protein ligase TRIM21	gwas
STAU2	HGNC:11371	ENSG00000040341	Q9NUL3	Double-stranded RNA-binding protein Staufen homolog 2	gwas
STIM1	HGNC:11386	ENSG00000167323	Q13586	Stromal interaction molecule 1	gwas
STX1A	HGNC:11433	ENSG00000106089	Q16623	Syntaxin-1A	gwas
SURF1	HGNC:11474	ENSG00000148290	Q15526	Surfeit locus protein 1	gwas
SURF2	HGNC:11475	ENSG00000148291	Q15527	Surfeit locus protein 2	gwas
SURF4	HGNC:11476	ENSG00000148248	O15260	Surfeit locus protein 4	gwas
MED22	HGNC:11477	ENSG00000148297	Q15528	Mediator of RNA polymerase II transcription subunit 22	gwas
SURF6	HGNC:11478	ENSG00000148296	O75683	Surfeit locus protein 6	gwas
TAF10	HGNC:11543	ENSG00000166337	Q12962	Transcription initiation factor TFIID subunit 10	gwas
TBL2	HGNC:11586	ENSG00000106638	Q9Y4P3	Transducin beta-like protein 2	gwas
ELOC	HGNC:11617	ENSG00000154582	Q15369	Elongin-C	gwas
TNF	HGNC:11892	ENSG00000232810	P01375	Tumor necrosis factor	gwas
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gwas
TRPC2	HGNC:12334	ENSG00000182048		transient receptor potential cation channel subfamily C member 2 (pseudogene)	gwas
TSSC2	HGNC:12384	ENSG00000223756		tumor suppressing subtransferable candidate 2 (pseudogene)	gwas
PHLDA2	HGNC:12385	ENSG00000181649	Q53GA4	Pleckstrin homology-like domain family A member 2	gwas
TSSC4	HGNC:12386	ENSG00000184281	Q9Y5U2	U5 small nuclear ribonucleoprotein TSSC4	gwas
MYOT	HGNC:12399	ENSG00000120729	Q9UBF9	Myotilin	gwas
TUB	HGNC:12406	ENSG00000166402	P50607	Tubby protein homolog	gwas
UBQLN3	HGNC:12510	ENSG00000175520	Q9H347	Ubiquilin-3	gwas
UCP1	HGNC:12517	ENSG00000109424	P25874	Mitochondrial brown fat uncoupling protein 1	gwas
MLXIPL	HGNC:12744	ENSG00000009950	Q9NP71	Carbohydrate-responsive element-binding protein	gwas
REXO4	HGNC:12820	ENSG00000148300	Q9GZR2	RNA exonuclease 4	gwas
ZNF195	HGNC:12986	ENSG00000005801	O14628	Zinc finger protein 195	gwas
ZNF214	HGNC:13006	ENSG00000149050	Q9UL59	Zinc finger protein 214	gwas
ZNF215	HGNC:13007	ENSG00000149054	Q9UL58	Zinc finger protein 215	gwas
C11orf21	HGNC:13231	ENSG00000110665	Q9P2W6	Uncharacterized protein C11orf21	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCL7B	B-cell CLL/lymphoma 7 protein family member B	Positive regulator of apoptosis.
TRIM34	E3 ubiquitin-protein ligase TRIM34	Functions as antiviral protein and contributes to the defense against retroviral infections.
TRIM3	Tripartite motif-containing protein 3	E3 ubiquitin ligase that plays essential roles in neuronal functions such as regulation of neuronal plasticity, learning, and memory.
RPL7A	Large ribosomal subunit protein eL8	Component of the large ribosomal subunit.
RRM1	Ribonucleoside-diphosphate reductase large subunit	Provides the precursors necessary for DNA synthesis.
RYR3	Ryanodine receptor 3	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a role in triggering muscle contraction.
SCO1	Cytochrome c oxidase assembly factor SCO1	Copper metallochaperone essential for the maturation of cytochrome c oxidase subunit II (MT-CO2/COX2).
SDC4	Syndecan-4	Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP.
SEMG1	Semenogelin-1	Predominant protein in semen.
SEMG2	Semenogelin-2	Participates in the formation of a gel matrix (sperm coagulum) entrapping the accessory gland secretions and ejaculated spermatozoa.
SF3B3	Splicing factor 3B subunit 3	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
ST3GAL2	CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 2	A beta-galactoside alpha2-3 sialyltransferase primarily involved in terminal sialylation of ganglio and globo series glycolipids.
SLC67A1	Solute carrier family 67 member A1	May act as a transporter of organic cations based on a proton efflux antiport mechanism.
SLPI	Antileukoproteinase	Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G.
SMARCA5	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5	ATPase that possesses intrinsic ATP-dependent nucleosome-remodeling activity.
SMPD1	Sphingomyelin phosphodiesterase	Converts sphingomyelin to ceramide.
SPINT1	Kunitz-type protease inhibitor 1	Inhibitor of HGFAC.
TRIM21	E3 ubiquitin-protein ligase TRIM21	E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2.
STAU2	Double-stranded RNA-binding protein Staufen homolog 2	RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite.
STIM1	Stromal interaction molecule 1	Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels.
STX1A	Syntaxin-1A	Plays an essential role in hormone and neurotransmitter calcium-dependent exocytosis and endocytosis.
SURF1	Surfeit locus protein 1	Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.
SURF4	Surfeit locus protein 4	Endoplasmic reticulum cargo receptor that mediates the export of lipoproteins by recruiting cargos into COPII vesicles to facilitate their secretion.
MED22	Mediator of RNA polymerase II transcription subunit 22	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
SURF6	Surfeit locus protein 6	Binds to both DNA and RNA in vitro, with a stronger binding capacity for RNA.
TAF10	Transcription initiation factor TFIID subunit 10	The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.
ELOC	Elongin-C	SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites.
TNF	Tumor necrosis factor	Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
TNFAIP3	Tumor necrosis factor alpha-induced protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
PHLDA2	Pleckstrin homology-like domain family A member 2	Plays a role in regulating placenta growth.
TSSC4	U5 small nuclear ribonucleoprotein TSSC4	Protein associated with the U5 snRNP, during its maturation and its post-splicing recycling and which is required for spliceosomal tri-snRNP complex assembly in the nucleus.
MYOT	Myotilin	Component of a complex of multiple actin cross-linking proteins.
TUB	Tubby protein homolog	Functions in signal transduction from heterotrimeric G protein-coupled receptors.
UCP1	Mitochondrial brown fat uncoupling protein 1	Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to…
MLXIPL	Carbohydrate-responsive element-binding protein	Glucose-responsive transcription activator that regulates fatty acid synthesis and glycolysis.
ZNF195	Zinc finger protein 195	May be involved in transcriptional regulation.
ZNF214	Zinc finger protein 214	May be involved in transcriptional regulation.
ZNF215	Zinc finger protein 215	May be involved in transcriptional regulation.
KLRF1	Killer cell lectin-like receptor subfamily F member 1	Functions as an activating receptor involved in immunosurveillance upon binding to various ligands displayed at the surface of myeloid cells.
AVEN	Cell death regulator Aven	Protects against apoptosis mediated by Apaf-1.
ADAMTS13	A disintegrin and metalloproteinase with thrombospondin motifs 13	Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.
DCHS1	Protocadherin-16	Calcium-dependent cell-adhesion protein.
RBPJL	Recombining binding protein suppressor of hairless-like protein	Putative transcription factor, which cooperates with EBNA2 to activate transcription.
CHRNA10	Neuronal acetylcholine receptor subunit alpha-10	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits.
APOM	Apolipoprotein M	Probably involved in lipid transport.
DDX39B	Spliceosome RNA helicase DDX39B	Involved in nuclear export of spliced and unspliced mRNA.
PRRC2A	Protein PRRC2A	May play a role in the regulation of pre-mRNA splicing.
BAG6	Large proline-rich protein BAG6	ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins.
ABHD16A	Phosphatidylserine lipase ABHD16A	Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS).
LY6G5C	Lymphocyte antigen 6 complex locus protein G5c	May have a role in hematopoietic cell differentiation.

Protein-family classification

Druggable: 11 · Difficult: 15 · Unknown: 49 · Druggable fraction: 0.15

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
Other/Unknown	49	1.2×	0.540
Complement	1	3.6×	0.667
Transporter	2	2.1×	0.667
Transcription factor	11	1.2×	0.667
Ion channel	1	1.5×	0.738
Antibody/Immunoglobulin	3	1.2×	0.738
Scaffold/PPI	4	0.9×	0.819
Protease	1	0.5×	0.955
Enzyme (other)	3	0.5×	0.955

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCL7B	Other/Unknown	no		BCL7
TRIM34	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
TRIM3	Transcription factor	no		Znf_B-box, NHL_repeat, Filamin/ABP280_rpt
SNORD24	Other/Unknown	no
SNORD36A	Other/Unknown	no
SNORD36B	Other/Unknown	no
SNORD36C	Other/Unknown	no
RPL7A	Other/Unknown	no		Ribosomal_eL8_euk, Ribosomal_eL8-like_CS, Ribosomal_eL8/eL30/eS12/Gad45
RRM1	Enzyme (other)	yes	1.17.4.1	RNR_lg_C, ATP-cone_dom, RNR_R1-su_N
RYR3	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
SCO1	Other/Unknown	no		SCO1/SenC, Synth_of_cyt-c-oxidase_Sco1/2, Thioredoxin-like_sf
SDC4	Other/Unknown	no		Syndecan, Neurexin-like, Syndecan/Neurexin_dom
SEMG1	Other/Unknown	no		Semenogelin
SEMG2	Other/Unknown	no		Semenogelin
SF3B3	Scaffold/PPI	no		RSE1/DDB1/CPSF1_C, WD40/YVTN_repeat-like_dom_sf, Beta-prop_RSE1/DDB1/CPSF1_1st
ST3GAL2	Enzyme (other)	yes	2.4.99.2	Glyco_trans_29, Sialyl_trans, GT29-like_sf
SLC67A1	Transporter	yes		Tet-R_TetA/multi-R_MdtG-like, MFS, MFS_dom
SLC67A1-AS	Other/Unknown	no
SLPI	Other/Unknown	no		WAP_dom, Elafin-like_sf, WAP_four-disulfide_core
SMARCA5	Transcription factor	no		SNF2_N, SANT/Myb, Helicase_C-like
SMPD1	Enzyme (other)	yes	3.1.4.12	Calcineurin-like_PHP, SaposinB_dom, Saposin-like
SPINT1	Antibody/Immunoglobulin	yes		LDrepeatLR_classA_rpt, Kunitz_BPTI, MANSC_N
TRIM21	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
STAU2	Other/Unknown	no		dsRBD_dom, Staufen_C, STAU2_DSRM_2
STIM1	Other/Unknown	no		SAM, SAM/pointed_sf, SOAR_STIM1/2
STX1A	Other/Unknown	no		T_SNARE_dom, Syntaxin_N, Syntaxin/epimorphin_CS
SURF1	Other/Unknown	no		Surf1/Shy1, Surf1/Surf4
SURF2	Other/Unknown	no		Surf2
SURF4	Other/Unknown	no		Surf4, Surf1/Surf4
MED22	Other/Unknown	no		Med22
SURF6	Other/Unknown	no		SURF6, Rrp14/SURF6_C
TAF10	Other/Unknown	no		TAF10
TBL2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_PAC1
ELOC	Other/Unknown	no		SKP1-like, SKP1/BTB/POZ_sf, Skp1_comp_POZ
TNF	Other/Unknown	no		TNF_alpha, TNF_dom, TNF
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
TRPC2	Other/Unknown	no
TSSC2	Other/Unknown	no
PHLDA2	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, PHLA1/2/3
TSSC4	Other/Unknown	no		TSSC4
MYOT	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
TUB	Other/Unknown	no		Tubby_C, Tubby_N, Tubby_C_CS
UBQLN3	Other/Unknown	no		Ubiquitin-like_dom, STI1_HS-bd, UBA-like_sf
UCP1	Transporter	yes		MCP, MCP_transmembrane, MCP_dom_sf
MLXIPL	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, Max-like/E-box_TFs
REXO4	Other/Unknown	no		RNaseH-like_sf, Ribonucl_H, RNaseH_sf
ZNF195	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZNF214	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZNF215	Transcription factor	no		KRAB, SCAN_dom, Znf_C2H2_type
C11orf21	Other/Unknown	no		DUF4620

Expression context

Cohort genes with no expression data: 0.

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)	1
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	11
monocyte	9
left testis	8
male germ line stem cell (sensu Vertebrata) in testis	8
leukocyte	7
right hemisphere of cerebellum	7
sural nerve	7
right testis	7
ganglionic eminence	6
ventricular zone	6
mucosa of transverse colon	6
apex of heart	5
liver	5
primordial germ cell in gonad	5
cortical plate	5
right lobe of liver	5
gastrocnemius	5
sperm	4
blood	4
buccal mucosa cell	4

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCL7B	287	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, apex of heart
TRIM34	134	ubiquitous	yes	monocyte, leukocyte, lymph node
TRIM3	238	ubiquitous	yes	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
SNORD24	45		yes	sural nerve, liver, calcaneal tendon
SNORD36A	11	tissue_specific	yes	sural nerve, liver, lung
SNORD36B	25	tissue_specific	yes	sural nerve, liver, lung
SNORD36C	115	tissue_specific	yes	sural nerve, granulocyte, skeletal muscle tissue
RPL7A	134	ubiquitous	marker	primordial germ cell in gonad, islet of Langerhans, left ovary
RRM1	296	ubiquitous	marker	ventricular zone, ganglionic eminence, cervix squamous epithelium
RYR3	233	broad	marker	diaphragm, sural nerve, right hemisphere of cerebellum
SCO1	243	ubiquitous	marker	left ventricle myocardium, primordial germ cell in gonad, mucosa of transverse colon
SDC4	290	ubiquitous	marker	olfactory segment of nasal mucosa, nasal cavity epithelium, cartilage tissue
SEMG1	62	tissue_specific	marker	seminal vesicle, sperm, male germ cell
SEMG2	45	tissue_specific	marker	seminal vesicle, sperm, male germ cell
SF3B3	296	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
ST3GAL2	248	ubiquitous	marker	blood, tendon of biceps brachii, endothelial cell
SLC67A1	132	ubiquitous	marker	mucosa of transverse colon, duodenum, right lobe of liver
SLC67A1-AS	124	broad	marker	mucosa of transverse colon, duodenum, transverse colon
SLPI	262	broad	marker	trachea, bronchus, bronchial epithelial cell
SMARCA5	300	ubiquitous	marker	ventricular zone, calcaneal tendon, buccal mucosa cell
SMPD1	262	ubiquitous	marker	type B pancreatic cell, stromal cell of endometrium, islet of Langerhans
SPINT1	228	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, jejunal mucosa
TRIM21	193	ubiquitous	marker	granulocyte, leukocyte, monocyte
STAU2	279	ubiquitous	marker	cortical plate, ganglionic eminence, prefrontal cortex
STIM1	237	ubiquitous	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
STX1A	186	ubiquitous	marker	right frontal lobe, right hemisphere of cerebellum, prefrontal cortex
SURF1	183	ubiquitous	marker	apex of heart, body of pancreas, right lobe of liver
SURF2	134	ubiquitous	marker	left testis, right testis, testis
SURF4	134	ubiquitous	marker	islet of Langerhans, stromal cell of endometrium, duodenum
MED22	134	ubiquitous	yes	cortical plate, granulocyte, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 55.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNF	11,116
SMARCA5	6,214
DDX39B	5,600
RRM1	4,985
SF3B3	4,351
SMC4	4,120
ELOC	4,044
TNFAIP3	3,716
TRIM21	3,613
MRPL17	3,339

Intra-cohort edges

A	B	Sources
ABHD16A	DDX39B	string_interaction
ABHD16A	GPANK1	string_interaction
ABHD16A	LST1	string_interaction
ABHD16A	LY6G5B	string_interaction
ABHD16A	LY6G5C	string_interaction
ABHD16A	PRRC2A	string_interaction
APOM	GPANK1	string_interaction
BAG6	MRPL17	intact
BAG6	PRRC2A	string_interaction
BCL7B	MLXIPL	string_interaction
BCL7B	TBL2	string_interaction
C11orf21	TSPAN32	string_interaction
C11orf21	TSSC4	string_interaction
DDX39B	LST1	string_interaction
GPANK1	LY6G5B	string_interaction
GPANK1	LY6G5C	string_interaction
GPANK1	LY6G6C	string_interaction
GPANK1	PRRC2A	string_interaction
LST1	TNF	string_interaction
LY6G5B	LY6G5C	string_interaction
LY6G5B	LY6G6C	string_interaction
LY6G5B	LY6G6F	string_interaction
LY6G5B	MPIG6B	string_interaction
LY6G5C	LY6G6C	string_interaction
LY6G5C	LY6G6F	string_interaction
LY6G6C	LY6G6F	string_interaction
LY6G6C	MPIG6B	string_interaction
LY6G6F	MPIG6B	string_interaction
MED22	SURF1	string_interaction
MED22	SURF2	string_interaction
MED22	SURF6	string_interaction
MLXIPL	TBL2	string_interaction
PHLDA2	SLC67A1	string_interaction
PHLDA2	SLC67A1-AS	string_interaction
PHLDA2	TSPAN32	string_interaction
PHLDA2	TSSC4	string_interaction
REXO4	RPL7A	intact
SCO1	SURF1	string_interaction
SEMG1	SEMG2	string_interaction
SEMG1	SLPI	string_interaction
SEMG2	SLPI	string_interaction
SLC67A1	SLC67A1-AS	string_interaction
SLC67A1	TSPAN32	string_interaction
SLC67A1	TSSC4	string_interaction
STIM1	SURF4	string_interaction
SURF1	SURF2	string_interaction
SURF1	SURF4	string_interaction
SURF1	SURF6	string_interaction
SURF2	SURF4	string_interaction
SURF2	SURF6	string_interaction

Structural data

PDB: 39 · AlphaFold-only: 29 · No structure: 7

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ELOC	Q15369	225
RPL7A	P62424	200
MRPL17	Q9NRX2	87
SF3B3	Q15393	67
TNF	P01375	52
TAF10	Q12962	48
TRIM21	P19474	20
TNFAIP3	P21580	17
DDX39B	Q13838	17
SMARCA5	O60264	15
RRM1	P23921	12
MED22	Q15528	11
RYR3	Q15413	10
SCO1	O75880	10
BAG6	P46379	10
UCP1	P25874	8
SPINT1	O43278	7
MLXIPL	Q9NP71	7
STIM1	Q13586	6
SDC4	P31431	5
ADAMTS13	Q76LX8	5
PRDM9	Q9NQV7	5
SEMG1	P04279	4
SMPD1	P17405	4
SURF6	O75683	4
BCL7B	Q9BQE9	3
TRIM3	O75382	3
TSSC4	Q9Y5U2	3
UBQLN3	Q9H347	3
APOM	O95445	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABHD16A	O95870	89.90
TBL2	Q9Y4P3	87.11
SLC67A1	Q96BI1	86.91
PHLDA2	Q53GA4	86.07
ST3GAL2	Q16842	85.68
STX1A	Q16623	84.94
LY6G6C	O95867	84.90
SURF4	O15260	84.65
CHRNA10	Q9GZZ6	82.93
SURF1	Q15526	82.62
RBPJL	Q9UBG7	80.58
LY6G5C	Q5SRR4	79.53
LY6G6F	Q5SQ64	77.31
LY6G5B	Q8NDX9	76.66
TSPAN32	Q96QS1	72.74
GPANK1	O95872	71.48
REXO4	Q9GZR2	71.20
SURF2	Q15527	71.05
STAU2	Q9NUL3	70.34
LST1	O00453	70.03
ZNF214	Q9UL59	62.28
KCNQ1DN	Q9H478	60.24
AVEN	Q9NQS1	58.86
C11orf21	Q9P2W6	55.54
ZNF195	O14628	55.00
ZNF215	Q9UL58	49.68
PRRC2A	P48634	40.07
SLC67A1-AS	Q8N1D0	32.95
SEMG2	Q02383	30.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 489. Enrichment computed across 250 evidence-associated genes (158 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 158 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Expression and translocation of olfactory receptors	59	10.5×	1e-42	OR51B2, OR51B4, OR51G1, OR51L1, OR51A2, OR52E2, OR56A1, OR5P2 (+51 more)
Olfactory Signaling Pathway	10	9.2×	3e-05	OR51L1, OR5P3, OR56A4, OR10A6, OR51D1, OR51E1, OR51E2, OR52B6 (+2 more)
Interferon gamma signaling	7	5.6×	0.042	TRIM34, TRIM3, TRIM21, TRIM5, TRIM6, TRIM22, TRIM68
Attachment of GPI anchor to uPAR	2	16.1×	0.628	PIGT, PIGU
Retrograde transport at the Trans-Golgi-Network	4	5.6×	0.628	SYS1, ARFIP2, COG4, SCOC
Defective SLC22A18 causes lung cancer (LNCR) and embryonal rhabdomyosarcoma 1 (RMSE1)	1	72.3×	0.738	SLC67A1
Defects of platelet adhesion to exposed collagen	1	72.3×	0.738	ADAMTS13
Mitochondrial Uncoupling	1	36.1×	0.738	UCP1
Defective MMAA causes MMA, cblA type	1	36.1×	0.738	MMAA
Defective MUT causes MMAM	1	36.1×	0.738	MMAA
Diseases of mitochondrial beta oxidation	1	36.1×	0.738	MMAA
Diseases of propionyl-CoA catabolism	1	36.1×	0.738	MMAA
Synthesis And Processing Of GAG, GAGPOL Polyproteins	1	24.1×	0.738	MVB12B
Toxicity of botulinum toxin type C (botC)	1	24.1×	0.738	STX1A
Synthesis of IPs in the nucleus	1	18.1×	0.738	IPPK
Catecholamine biosynthesis	1	18.1×	0.738	DDC
Diseases of hemostasis	1	18.1×	0.738	ADAMTS13
Enhanced cleavage of VWF variant by ADAMTS13	1	18.1×	0.738	ADAMTS13
Defective VWF cleavage by ADAMTS13 variant	1	18.1×	0.738	ADAMTS13
PKA-mediated phosphorylation of key metabolic factors	1	14.5×	0.738	MLXIPL
The fatty acid cycling model	1	14.5×	0.738	UCP1
Serotonin and melatonin biosynthesis	1	14.5×	0.738	DDC
Muscarinic acetylcholine receptors	1	14.5×	0.738	CHRM5
Propionyl-CoA catabolism	1	14.5×	0.738	MMAA
Signaling by MST1	1	14.5×	0.738	SPINT1
Acetylcholine inhibits contraction of outer hair cells	1	14.5×	0.738	CHRNA10
Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK	1	14.5×	0.738	CSNK2B
Condensation of Prometaphase Chromosomes	2	13.1×	0.738	SMC4, CSNK2B
SUMO is proteolytically processed	1	12.1×	0.738	SENP5
TNFR1-mediated ceramide production	1	12.1×	0.738	TNF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 192 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to lipid	26	67.1×	8e-42	OR51B2, OR51B4, OR51G1, OR51L1, OR51A2, OR56A1, OR56A3, OR56A4 (+18 more)
sensory perception of smell	13	10.6×	1e-07	OR51B4, OR51M1, OR10A5, OR51I1, OR51I2, OR52D1, OR6A2, OR52A5 (+5 more)
NK T cell activation	4	58.5×	8e-05	KLRF1, BAG6, NCR3, CLEC2B
coagulation	2	87.8×	0.031	SEMG1, SEMG2
antiviral innate immune response	6	7.1×	0.037	SMARCA5, TRIM21, TNF, TRIM6, OTUD4, UBE2W
immune response-activating cell surface receptor signaling pathway	2	58.5×	0.046	BAG6, NCR3
positive regulation of serine-type endopeptidase activity	2	58.5×	0.046	SEMG1, SEMG2
negative regulation of flagellated sperm motility	2	58.5×	0.046	SEMG1, SEMG2
detection of chemical stimulus involved in sensory perception of smell	7	4.5×	0.100	OR10A4, OR10A5, OR10A6, OR2AG1, OR2AG2, OR2D3, OR6A2
GPI anchored protein biosynthesis	2	29.3×	0.178	PIGT, PIGU
regulation of gene expression	8	3.5×	0.193	TRIM34, TRIM21, PHLDA2, PRDM9, TRIM5, TRIM6, TRIM22, TRIM68
negative regulation of oxidative phosphorylation	2	25.1×	0.205	TNF, MLXIPL
gastric acid secretion	2	21.9×	0.205	CCKBR, CHRM5
attachment of GPI anchor to protein	2	21.9×	0.205	PIGT, PIGU
regulation of defense response to virus	2	21.9×	0.205	TSPAN32, ELMOD2
establishment of protein localization to telomere	2	21.9×	0.205	ACD, ZNF827
negative regulation of toll-like receptor 5 signaling pathway	1	87.8×	0.225	TNFAIP3
macrophage fusion	1	87.8×	0.225	CD81
CD4-positive, alpha-beta T cell costimulation	1	87.8×	0.225	CD81
SAGA complex assembly	1	87.8×	0.225	TAF10
positive regulation of translational initiation by iron	1	87.8×	0.225	TNF
host-mediated perturbation of symbiont process	1	87.8×	0.225	SLPI
regulation of vascular wound healing	1	87.8×	0.225	TNFAIP3
negative regulation of branching involved in lung morphogenesis	1	87.8×	0.225	TNF
negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	1	87.8×	0.225	TNFAIP3
establishment of protein localization to vacuole	1	87.8×	0.225	TNFAIP3
regulation of primary metabolic process	1	87.8×	0.225	TRIM34
negative regulation of bile acid secretion	1	87.8×	0.225	TNF
regulation of cytoplasmic translational fidelity	1	87.8×	0.225	AARS1
response to Gram-negative bacterium	1	87.8×	0.225	TNF

Therapeutics

Drugs indicated for this disease

17 approved, 29 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Amodiaquine	Approved (phase 4)
Artemether	Approved (phase 4)
Artemisinin	Approved (phase 4)
Artenimol	Approved (phase 4)
Artesunate	Approved (phase 4)
Atovaquone	Approved (phase 4)
Chloroquine	Approved (phase 4)
Halofantrine	Approved (phase 4)
Hydroxychloroquine	Approved (phase 4)
Lumefantrine	Approved (phase 4)
Mefloquine	Approved (phase 4)
Primaquine	Approved (phase 4)
Proguanil	Approved (phase 4)
Pyrimethamine	Approved (phase 4)
Quinine	Approved (phase 4)
Sulfadiazine	Approved (phase 4)
Tafenoquine	Approved (phase 4)
Abamectin	Phase 3 (in late-stage trials)
Acetaminophen	Phase 3 (in late-stage trials)
Albendazole	Phase 3 (in late-stage trials)
Artemisin	Phase 3 (in late-stage trials)
Azithromycin	Phase 3 (in late-stage trials)
Chlorproguanil	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Clindamycin	Phase 3 (in late-stage trials)
Cytarabine	Phase 3 (in late-stage trials)
Dapsone	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
Fosmidomycin	Phase 3 (in late-stage trials)
Ivermectin	Phase 3 (in late-stage trials)
MATRIX-M1 ADJUVANT	Phase 3 (in late-stage trials)
Mannitol	Phase 3 (in late-stage trials)
Piperaquine	Phase 3 (in late-stage trials)
Prasterone	Phase 3 (in late-stage trials)
Pyronaridine	Phase 3 (in late-stage trials)
Rabies Vaccine	Phase 3 (in late-stage trials)
Retinol	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sulfadoxine	Phase 3 (in late-stage trials)
Sulfalene	Phase 3 (in late-stage trials)
Sulfamethoxazole	Phase 3 (in late-stage trials)
Trimethoprim	Phase 3 (in late-stage trials)
Tromethamine	Phase 3 (in late-stage trials)
Yellow Fever Vaccine	Phase 3 (in late-stage trials)
Zinc Ion	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Epoetin Beta, Hepatitis B Virus Vaccine Inactivated, Lumefantrine Co-Artemether, Nitric Oxide, Typhoid Vi Polysaccharide Vaccine.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 9 · Phased (≥1): 10 · Undrugged: 65

Druggability breadth: 48 of 250 evidence-associated genes (19%) 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
RPL7A	GENTAMICIN SULFATE
SDC4	BRIGATINIB
SF3B3	TACROLIMUS ANHYDROUS
SMPD1	IMIPRAMINE
STIM1	TERIFLUNOMIDE
TNF	PREDNISOLONE
CHRNA10	ACETYLCHOLINE
ABHD16A	ORLISTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNF	12	4
SF3B3	3	4
SMPD1	3	4
SDC4	2	4
STIM1	2	4
CHRNA10	2	4
RPL7A	1	4
RRM1	1	3
ABHD16A	1	4
SMC4	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL7A
BRIGATINIB	4	SDC4
CRIZOTINIB	4	SDC4
TACROLIMUS ANHYDROUS	4	SF3B3
IMIPRAMINE	4	SMPD1
CHLORPROMAZINE	4	SMPD1
TERIFLUNOMIDE	4	STIM1
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	TNF
LENALIDOMIDE	4	TNF
ACETYLCHOLINE	4	CHRNA10
ORLISTAT	4	ABHD16A
TRIAPINE	3	RRM1
MARIMASTAT	3	TNF
IBERDOMIDE	3	TNF
MOLIBRESIB	2	SF3B3, SMC4
FENDILINE	2	SMPD1
ZEGOCRACTIN	2	STIM1
DORAMAPIMOD	2	TNF
AVADOMIDE	2	TNF
MIZACORAT	2	TNF
LINPERLISIB	2	TNF
ROLIPRAM	2	TNF
STILONIUM IODIDE	2	CHRNA10
TRICHOSTATIN	1	SF3B3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
TNF	193	Binding:162, Functional:31
ELOC	97	Binding:97
CHRNA10	92	Binding:89, Functional:2, ADMET:1
RPL7A	90	Binding:90
RRM1	83	Binding:80, Functional:3
PRDM9	60	Binding:58, Functional:2
SMPD1	42	Binding:40, Functional:2
SF3B3	41	Binding:41
STIM1	35	Binding:33, Functional:1, ADMET:1
ABHD16A	13	Binding:13
SURF4	7	Binding:7
SMC4	7	Binding:7
ADAMTS13	3	Binding:3
RYR3	2	Binding:2
BCL7B	1	Binding:1
SDC4	1	Binding:1
SLC67A1	1	Binding:1
SMARCA5	1	Binding:1
SPINT1	1	Binding:1
TBL2	1	Binding:1
TNFAIP3	1	Binding:1
DDX39B	1	Binding:1
PRRC2A	1	Binding:1
BAG6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RRM1	1.17.4.1	ribonucleoside-diphosphate reductase
ST3GAL2	2.4.99.2	beta-D-galactosyl-(1->3)-N-acetyl-beta-D-galactosaminide alpha-2,3-sialyltransferase
SMPD1	3.1.4.12	sphingomyelin phosphodiesterase
ADAMTS13	3.4.24.87	ADAMTS13 endopeptidase
PRDM9	2.1.1.359	[histone H3]-lysine36 N-trimethyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TNF	193

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

27 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)
GENTAMICIN SULFATE	4	RPL7A
BRIGATINIB	4	SDC4
CRIZOTINIB	4	SDC4
TACROLIMUS ANHYDROUS	4	SF3B3
IMIPRAMINE	4	SMPD1
CHLORPROMAZINE	4	SMPD1
TERIFLUNOMIDE	4	STIM1
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	TNF
LENALIDOMIDE	4	TNF
ACETYLCHOLINE	4	CHRNA10
ORLISTAT	4	ABHD16A
TRIAPINE	3	RRM1
MARIMASTAT	3	TNF
IBERDOMIDE	3	TNF
MOLIBRESIB	2	SF3B3, SMC4
FENDILINE	2	SMPD1
ZEGOCRACTIN	2	STIM1
DORAMAPIMOD	2	TNF
AVADOMIDE	2	TNF
MIZACORAT	2	TNF
LINPERLISIB	2	TNF
ROLIPRAM	2	TNF
STILONIUM IODIDE	2	CHRNA10
TRICHOSTATIN	1	SF3B3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	RPL7A, SDC4, SF3B3, SMPD1, STIM1, TNF, CHRNA10, ABHD16A
B	Phased (≥1) drug, not yet approved	2	RRM1, SMC4
C	Druggable family + PDB, no drug	6	RYR3, SPINT1, MYOT, UCP1, ADAMTS13, CSMD1
D	Druggable family + AlphaFold only, no drug	3	ST3GAL2, SLC67A1, LY6G6F
E	Difficult family or no structure, no drug	56	BCL7B, TRIM34, TRIM3, SNORD24, SNORD36A, SNORD36B, SNORD36C, SCO1, SEMG1, SEMG2 (+46 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRRC2A	1	ABHD16A
GPANK1	0	ABHD16A
LY6G5C	0	ABHD16A
LST1	0	ABHD16A
BCL7B	1	—
TRIM34	0	—
TRIM3	0	—
SNORD24	0	—
SNORD36A	0	—
SNORD36B	0	—
SNORD36C	0	—
RYR3	2	—
SCO1	0	—
SEMG1	0	—
SEMG2	0	—
ST3GAL2	0	—
SLC67A1	1	—
SLC67A1-AS	0	—
SLPI	0	—
SMARCA5	1	—
SPINT1	1	—
TRIM21	0	—
STAU2	0	—
STX1A	0	—
SURF1	0	—
SURF2	0	—
SURF4	7	—
MED22	0	—
SURF6	0	—
TAF10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 889.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	349
PHASE1	160
PHASE4	126
PHASE3	110
PHASE2	84
PHASE1/PHASE2	42
PHASE2/PHASE3	15
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05788094	PHASE4	RECRUITING	ACT vs CQ With Tafenoquine for P. Vivax Mono-infection
NCT06601712	PHASE4	RECRUITING	Post-discharge Malaria Chemoprevention Implementation Trial in Benin
NCT06624631	PHASE4	RECRUITING	PDMC Implementation Trial in Kenya
NCT06967519	PHASE4	RECRUITING	OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa
NCT07194668	PHASE4	NOT_YET_RECRUITING	R21/MM Dosing, Presentations, and Preservatives
NCT07246525	PHASE4	NOT_YET_RECRUITING	Intermittent Preventive Treatment of Malaria in School-age Children to Decrease Community Transmission
NCT00119145	PHASE4	COMPLETED	Kintampo Trial of Combination Therapy for Malaria
NCT00125489	PHASE4	COMPLETED	CQSP in Malawi: Chloroquine and Sulfadoxine-pyrimethamine Efficacy for the Treatment of Malaria in Malawi
NCT00126217	PHASE4	TERMINATED	Revaccination of Young Children With Bacille Calmette Guerin (BCG) Vaccine
NCT00130065	PHASE4	COMPLETED	The Effect of Folic Acid on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
NCT00137566	PHASE4	UNKNOWN	The Effect of Paracetamol in the Treatment of Non-severe Malaria in Children in Guinea-Bissau
NCT00137657	PHASE4	COMPLETED	Impact of Cotrimoxazole Prophylaxis for HIV-Infected Adults on Antifolate Resistance
NCT00140361	PHASE4	COMPLETED	Efficacy of Sulphadoxine-pyrimethamine and Artemisinin-containing Combination Therapy for Malaria
NCT00144352	PHASE4	COMPLETED	In-Vivo Response of P. Falciparum to Antimalarial Treatment in HIV-Infected and HIV-Uninfected Adults
NCT00146692	PHASE4	COMPLETED	A Trial of Improved Financial Access to Healthcare in Ghana
NCT00146796	PHASE4	COMPLETED	A Randomised Trial of Rapid Diagnostic Tests in the Diagnosis of Malaria in Tanzania
NCT00164255	PHASE4	COMPLETED	Efficacy of Combination Therapy for Prevention of Effects of Malaria During Pregnancy
NCT00167739	PHASE4	COMPLETED	Treatment of Malaria With Quinine Plus Sulfadoxine-Pyrimethamine
NCT00167843	PHASE4	COMPLETED	Reducing the Effects of Malaria in Children by Administering Repeated Preventive Doses
NCT00168948	PHASE4	UNKNOWN	Intermittent Antimalaria Treatment With SP in African Children
NCT00206739	PHASE4	COMPLETED	Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infants
NCT00238017	PHASE4	UNKNOWN	Efficacy and Safety of Amodiaquine and Amodiaquine-Artesunate
NCT00290420	PHASE4	WITHDRAWN	Prevention of P. Vivax Malaria During Pregnancy in Bolivia
NCT00294580	PHASE4	COMPLETED	Early Childhood Malaria Prevention With Maloprim in The Gambia
NCT00317590	PHASE4	COMPLETED	Effectiveness and Cost-Effectiveness of a Rapid Diagnostic Test for Malaria
NCT00336375	PHASE4	COMPLETED	Treatment of Uncomplicated Childhood Malaria in Tanzania by Artemether+Lumefantrine - Efficacy and Genotyping
NCT00351013	PHASE4	COMPLETED	The Use of Homeopathic-Based Treatment Approaches to Reduce the Prevalence of Malaria in Depressed Communities
NCT00376155	PHASE4	COMPLETED	Comparison of Two Strategies for the Delivery of IPTc
NCT00386750	PHASE4	TERMINATED	Safety of Artemether - Lumefantrine, and Other Malaria Drugs and Their Effect on the Auditory Function
NCT00421473	PHASE4	COMPLETED	Drug Interaction Study Between Atovaquone and Antiretroviral Agents in HIV-1 Infected Patients
NCT00425763	PHASE4	COMPLETED	Efficacy of Amodiaquine-artesunate in Children Aged 6-59 Months With Uncomplicated P. Falciparum Malaria
NCT00444106	PHASE4	COMPLETED	Evaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function
NCT00445796	PHASE4	COMPLETED	Arsucam® (Artesunate + Amiodaquine) Efficacy and TOLerance
NCT00451139	PHASE4	COMPLETED	Ototoxicity of Artemether / Lumefantrine (Coartem) and Other Antimalarials
NCT00452907	PHASE4	COMPLETED	ACT MALI: Treatment of Malaria Based on Combination Therapies
NCT00453856	PHASE4	TERMINATED	Efficacy of Sulfadoxine-Pyrimethamine for Treating Malaria in Gabonese Children
NCT00454961	PHASE4	COMPLETED	Effectiveness of Artemether-Lumefantrine for Malaria Treatment of Children at Community Level in Tanzania
NCT00465257	PHASE4	SUSPENDED	Efficacy of Artesunate + Amodiaquine Four Years After Its Introduction in Zanzibar
NCT00493922	PHASE4	COMPLETED	Trial of Rapid Diagnostic Tests in Rural Ghana
NCT00495508	PHASE4	COMPLETED	Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AMODIAQUINE	4	93
PRIMAQUINE	4	82
CHLOROQUINE	4	50
ARTESUNATE	4	41
LUMEFANTRINE	4	23
ARTEMETHER	4	19
PYRIMETHAMINE	4	17
SULFADOXINE	4	16
MEFLOQUINE	4	14
QUININE	4	12
CLINDAMYCIN	4	9
PROGUANIL	4	8
ATOVAQUONE	4	7
IVERMECTIN	4	7
ARTENIMOL	4	6
TAFENOQUINE	4	6
ALBENDAZOLE	4	5
RETINOL	4	5
FOLIC ACID	4	3
PRAZIQUANTEL	4	3
TOCOFERSOLAN	4	3
AZITHROMYCIN	4	2
DAPSONE	4	2
EFAVIRENZ	4	2
HEPATITIS B VIRUS HBSAG SURFACE PROTEIN ANTIGEN	4	2
HYDROXYUREA	4	2
LAMIVUDINE	4	2
LOPINAVIR	4	2
METHYLENE BLUE	4	2
METHYLENE BLUE ANHYDROUS	4	2