Aids

Summary

AIDS (MONDO:0012268) is a disease with 19 cohort genes (17 GWAS associations across 4 studies) and 706 clinical trials. Top therapeutic interventions include darunavir, lamivudine, and maraviroc.

At a glance

• Cohort genes: 19
• GWAS associations: 17
• Clinical trials: 706

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	AIDS
Mondo ID	MONDO:0012268
EFO	EFO:0000765
MeSH	D000163
DOID	DOID:635
NCIT	C2851
SNOMED CT	62479008
UMLS	C0001175
MedGen	99
Is cancer (heuristic)	no

Also known as: acquired immune deficiency · acquired immunodeficiency disease · acquired immunodeficiency syndrome, AIDS · AIDS · AIDS, acquired immunodeficiency syndrome

Data availability: 17 GWAS associations (4 studies).

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › T-cell immunodeficiency › AIDS

Related subtypes (2): congenital T-cell immunodeficiency, idiopathic CD4-positive T-lymphocytopenia

Genetics & variants

GWAS landscape

17 GWAS associations across 4 studies. Top hits map to 15 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2395029	3e-19	HCP5	G	3.47
rs11884476	3e-09	PARD3B	?	3.32
rs10484554	6e-08	LINC02571 - HLA-B	T
rs8321	5e-07	POLR1HASP, POLR1HASP, POLR1H	G
rs4118325	6e-07	LINC01661 - PRMT6	G	4.17
rs6467710	6e-07	DGKI	?	4.3
rs1522232	2e-06	SOX5, SOX5-AS1	C	2.22
rs11239930	2e-06	RNVU1-8 - NBPF13P	?	1.47
rs1360517	3e-06	PRDX1P1 - MPDZ	A	3.09
rs3108919	4e-06	RPS20P23 - RNU4-83P	C	2.13
rs10800098	4e-06	RXRG	A	3.29
rs7217319	4e-06	LINC02091	?	1.48
rs6441975	5e-06	CCR5AS	?	1.48
rs477687	6e-06	PITX1-AS1	?	1.55
rs1020064	7e-06	TGFBRAP1	G	2.94
rs1556032	9e-06	NFIB-AS1	C	2.05
rs1015164	9e-06	CCRL2	?	1.46

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST001060	Troyer JL	2011	755	0	Genome-wide association study implicates PARD3B-based AIDS restriction.
GCST000487	Le Clerc S	2009	85	2,049	Genomewide association study of a rapid progression cohort identifies new susceptibility alleles for AIDS (ANRS Genomewide Association Study 03).
GCST90041717	Jiang L	2021	78	208,730	A generalized linear mixed model association tool for biobank-scale data.
GCST000308	Limou S	2009	0	1,352	Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02).

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	15

MAF distribution

Bucket	Variants
common (>=0.05)	15
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	12
3_prime_UTR_variant	2
intergenic_variant	2
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2395029	6	31464003	T>G	0.03	non_coding_transcript_exon_variant	HCP5	3e-19	Tier 4: intronic/intergenic
rs11884476	2	205453869	C>G	0.06	intron_variant	PARD3B	3e-09	Tier 4: intronic/intergenic
rs10484554	6	31306778	C>T	0.13	intron_variant	LINC02571 - HLA-B	6e-08	Tier 4: intronic/intergenic
rs8321	6	30064745	A>C,T	0.05	3_prime_UTR_variant	POLR1HASP, POLR1HASP, POLR1H	5e-07	Tier 2: splice/UTR
rs4118325	1	107035210	G>A,T	0.19	intron_variant	LINC01661 - PRMT6	6e-07	Tier 4: intronic/intergenic
rs6467710	7	137519073	G>A,C	0.02	intron_variant	DGKI	6e-07	Tier 4: intronic/intergenic
rs1522232	12	24241438	T>C	0.48	intron_variant	SOX5, SOX5-AS1	2e-06	Tier 4: intronic/intergenic
rs11239930	1	147089017	G>A,T	0.42	intergenic_variant	RNVU1-8 - NBPF13P	2e-06	Tier 4: intronic/intergenic
rs1360517	9	13007130	T>A,C,G	0.06	intron_variant	PRDX1P1 - MPDZ	3e-06	Tier 4: intronic/intergenic
rs3108919	8	100829318	T>C	0.27	intergenic_variant	RPS20P23 - RNU4-83P	4e-06	Tier 4: intronic/intergenic
rs10800098	1	165439858	G>A	0.05	intron_variant	RXRG	4e-06	Tier 4: intronic/intergenic
rs7217319	17	189133	T>A,C,G	0.37	intron_variant	LINC02091	4e-06	Tier 4: intronic/intergenic
rs6441975	3	46386699	A>C,G,T	0.31	intron_variant	CCR5AS	5e-06	Tier 4: intronic/intergenic
rs477687	5	135132010	G>A,C,T	0.18	intron_variant	PITX1-AS1	6e-06	Tier 4: intronic/intergenic
rs1020064	2	105281283	T>C,G	0.23	intron_variant	TGFBRAP1	7e-06	Tier 4: intronic/intergenic
rs1556032	9	14446003	C>T	0.49	intron_variant	NFIB-AS1	9e-06	Tier 4: intronic/intergenic
rs1015164	3	46410189	A>C,G,T	0.31	3_prime_UTR_variant	CCRL2	9e-06	Tier 2: splice/UTR

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX5	Orphanet:313884	12p12.1 microdeletion syndrome
SOX5	Orphanet:313892	Developmental and speech delay due to SOX5 deficiency
SOX5	Orphanet:626	Large/giant congenital melanocytic nevus
MACROH2A1	Orphanet:1275	Brachydactyly-elbow wrist dysplasia syndrome
HLA-C	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)

Cohort genes → proteins

19 cohort genes, 18 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPH3AL	HGNC:10296	ENSG00000181031	Q9UNE2	Rab effector Noc2	gwas
RXRG	HGNC:10479	ENSG00000143171	P48443	Retinoic acid receptor RXR-gamma	gwas
SOX5	HGNC:11201	ENSG00000134532	P35711	Transcription factor SOX-5	gwas
TNF	HGNC:11892	ENSG00000232810	P01375	Tumor necrosis factor	gwas
POLR1H	HGNC:13182	ENSG00000066379	Q9P1U0	DNA-directed RNA polymerase I subunit RPA12	gwas
DDX39B	HGNC:13917	ENSG00000198563	Q13838	Spliceosome RNA helicase DDX39B	gwas
PARD3B	HGNC:14446	ENSG00000116117	Q8TEW8	Partitioning defective 3 homolog B	gwas
CCRL2	HGNC:1612	ENSG00000121797	O00421	C-C chemokine receptor-like 2	gwas
TGFBRAP1	HGNC:16836	ENSG00000135966	Q8WUH2	Transforming growth factor-beta receptor-associated protein 1	gwas
RNF39	HGNC:18064	ENSG00000204618	Q9H2S5	RING finger protein 39	gwas
MCCD1	HGNC:20668	ENSG00000204511	P59942	Mitochondrial coiled-coil domain protein 1	gwas
CYCSP5	HGNC:24416	ENSG00000227735		CYCS pseudogene 5	gwas
NBPF14	HGNC:25232	ENSG00000270629	Q5TI25	NBPF family member NBPF14	gwas
DGKI	HGNC:2855	ENSG00000157680	O75912	Diacylglycerol kinase iota	gwas
MACROH2A1	HGNC:4740	ENSG00000113648	O75367	Core histone macro-H2A.1	gwas
HLA-C	HGNC:4933	ENSG00000204525	P10321	HLA class I histocompatibility antigen, C alpha chain	gwas
LTB	HGNC:6711	ENSG00000227507	Q06643	Lymphotoxin-beta	gwas
LTF	HGNC:6720	ENSG00000012223	P02788	Lactotransferrin	gwas
MICB	HGNC:7091	ENSG00000204516	Q29980	MHC class I polypeptide-related sequence B	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPH3AL	Rab effector Noc2	Rab GTPase effector involved in the late steps of regulated exocytosis, both in endocrine and exocrine cells.
RXRG	Retinoic acid receptor RXR-gamma	Receptor for retinoic acid.
SOX5	Transcription factor SOX-5	Transcription factor involved in chondrocytes differentiation and cartilage formation.
TNF	Tumor necrosis factor	Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
POLR1H	DNA-directed RNA polymerase I subunit RPA12	Core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates.
DDX39B	Spliceosome RNA helicase DDX39B	Involved in nuclear export of spliced and unspliced mRNA.
PARD3B	Partitioning defective 3 homolog B	Putative adapter protein involved in asymmetrical cell division and cell polarization processes.
CCRL2	C-C chemokine receptor-like 2	Receptor for CCL19 and chemerin/RARRES2.
TGFBRAP1	Transforming growth factor-beta receptor-associated protein 1	Plays a role in the TGF-beta/activin signaling pathway.
RNF39	RING finger protein 39	Plays an inhibitory role in anti-RNA viral innate immunity by targeting the adapter DDX3X and promoting its ‘Lys-48’-linked polyubiquitination.
DGKI	Diacylglycerol kinase iota	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
MACROH2A1	Core histone macro-H2A.1	Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription.
HLA-C	HLA class I histocompatibility antigen, C alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity.
LTB	Lymphotoxin-beta	Cytokine that binds to LTBR/TNFRSF3.
LTF	Lactotransferrin	Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.
MICB	MHC class I polypeptide-related sequence B	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.

Protein-family classification

Druggable: 5 · Difficult: 6 · Unknown: 8 · Druggable fraction: 0.26

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
Nuclear receptor	1	20.3×	0.248
Transcription factor	5	2.2×	0.248
Antibody/Immunoglobulin	2	3.1×	0.319
Kinase	1	1.5×	0.778
GPCR	1	1.3×	0.778
Scaffold/PPI	1	0.9×	0.791
Other/Unknown	8	0.8×	0.924

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPH3AL	Transcription factor	no		Rab_BD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
RXRG	Nuclear receptor	yes		Retinoid-X_rcpt/HNF4, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
SOX5	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
TNF	Other/Unknown	no		TNF_alpha, TNF_dom, TNF
POLR1H	Transcription factor	no		Znf_TFIIS, Rpa12/Rpb9/Rpc10/TFS, DNA-dir_RNA_pol-M_15_CS
DDX39B	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd
PARD3B	Scaffold/PPI	no		PDZ, Par3/HAL_N, PDZ_sf
CCRL2	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, GPCR_Rhodpsn_7TM
TGFBRAP1	Transcription factor	no		Clathrin_H-chain/VPS_repeat, CNH_dom, VPS39/TGF_beta_rcpt-assoc_1
RNF39	Transcription factor	no		Znf_RING, B30.2/SPRY, SPRY_dom
MCCD1	Other/Unknown	no		MCCD1
CYCSP5	Other/Unknown	no
NBPF14	Other/Unknown	no		Olduvai_dom, NBPF
DGKI	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, Ankyrin_rpt
MACROH2A1	Other/Unknown	no		Histone_H2A, Macro_dom, H2A/H2B/H3
HLA-C	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig_C1-set, Ig-like_dom
LTB	Other/Unknown	no		TNF_C, TNF_dom, TNF
LTF	Other/Unknown	no		Transferrin-like_dom, Transferrin, Transferrin_Fe_BS
MICB	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog

Expression context

Cohort genes with no expression data: 0.

17 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)	0
broad (>20)	19
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	5
adenohypophysis	3
ventricular zone	3
monocyte	3
calcaneal tendon	2
cortical plate	2
male germ line stem cell (sensu Vertebrata) in testis	2
mucosa of transverse colon	2
primordial germ cell in gonad	2
sural nerve	2
spleen	2
body of pancreas	1
pancreas	1
hindlimb stylopod muscle	1
muscle of leg	1
synovial joint	1
bone marrow	1
cardiac muscle of right atrium	1
rectum	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPH3AL	160	broad	marker	body of pancreas, adenohypophysis, pancreas
RXRG	170	broad	marker	hindlimb stylopod muscle, adenohypophysis, muscle of leg
SOX5	221	ubiquitous	marker	cortical plate, calcaneal tendon, synovial joint
TNF	119	broad	marker	granulocyte, male germ line stem cell (sensu Vertebrata) in testis, bone marrow
POLR1H	133	ubiquitous	marker	granulocyte, mucosa of transverse colon, primordial germ cell in gonad
DDX39B	263	ubiquitous	marker	granulocyte, adenohypophysis, ventricular zone
PARD3B	200	ubiquitous	marker	sural nerve, cardiac muscle of right atrium, ventricular zone
CCRL2	185	broad	marker	mucosa of transverse colon, rectum, upper lobe of left lung
TGFBRAP1	254	ubiquitous	marker	secondary oocyte, middle temporal gyrus, stromal cell of endometrium
RNF39	130		marker	skin of abdomen, zone of skin, skin of leg
MCCD1	67	tissue_specific	marker	adult mammalian kidney, kidney, metanephros cortex
CYCSP5	97		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, corpus callosum
NBPF14	134	broad	marker	sural nerve, ventricular zone, monocyte
DGKI	185	broad	marker	cortical plate, lateral nuclear group of thalamus, calcaneal tendon
MACROH2A1	302	ubiquitous	marker	epithelium of nasopharynx, tongue squamous epithelium, monocyte
HLA-C	134	ubiquitous	marker	blood, right lung, spleen
LTB	130	broad	marker	granulocyte, spleen, lymph node
LTF	224	broad	marker	trachea, trabecular bone tissue, olfactory segment of nasal mucosa
MICB	133	ubiquitous	yes	granulocyte, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNF	11,116
DDX39B	5,600
LTF	3,836
MACROH2A1	3,047
CCRL2	2,489
SOX5	2,310
POLR1H	2,074
TGFBRAP1	1,799
PARD3B	1,701
RXRG	1,696

Intra-cohort edges

A	B	Sources
DDX39B	MCCD1	string_interaction
POLR1H	RNF39	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 9 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNF	P01375	52
LTF	P02788	34
DDX39B	Q13838	17
MACROH2A1	O75367	13
HLA-C	P10321	13
POLR1H	Q9P1U0	7
RXRG	P48443	2
MICB	Q29980	2
LTB	Q06643	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TGFBRAP1	Q8WUH2	87.47
CCRL2	O00421	77.93
DGKI	O75912	73.59
RPH3AL	Q9UNE2	68.57
MCCD1	P59942	66.57
RNF39	Q9H2S5	66.27
SOX5	P35711	58.95
PARD3B	Q8TEW8	55.56
NBPF14	Q5TI25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 53. Enrichment computed across 19 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mtb iron assimilation by chelation	1	1142.0×	0.035	LTF
TNFR2 non-canonical NF-kB pathway	2	36.2×	0.035	TNF, LTB
TNFR1-mediated ceramide production	1	190.3×	0.065	TNF
Metal sequestration by antimicrobial proteins	1	163.1×	0.065	LTF
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	2	17.4×	0.065	HLA-C, MICB
Endosomal/Vacuolar pathway	1	103.8×	0.085	HLA-C
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	87.8×	0.086	TNF
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	1	67.2×	0.089	LTB
DAP12 interactions	1	47.6×	0.089	HLA-C
RHOBTB2 GTPase cycle	1	47.6×	0.089	DDX39B
Effects of PIP2 hydrolysis	1	45.7×	0.089	DGKI
TNFR1-induced proapoptotic signaling	1	43.9×	0.089	TNF
TNF signaling	1	42.3×	0.089	TNF
Signaling by Retinoic Acid	1	40.8×	0.089	RXRG
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	39.4×	0.089	HLA-C
Positive epigenetic regulation of rRNA expression	1	34.6×	0.089	POLR1H
TNFR1-induced NF-kappa-B signaling pathway	1	33.6×	0.089	TNF
RNA Polymerase I Transcription Termination	1	32.6×	0.089	POLR1H
RNA Polymerase I Promoter Clearance	1	29.3×	0.091	POLR1H
RNA Polymerase I Transcription	1	28.6×	0.091	POLR1H
Negative epigenetic regulation of rRNA expression	1	25.9×	0.093	POLR1H
Interleukin-10 signaling	1	23.3×	0.093	TNF
Regulation of TNFR1 signaling	1	22.4×	0.093	TNF
Antimicrobial peptides	1	22.4×	0.093	LTF
RNA Polymerase I Transcription Initiation	1	22.4×	0.093	POLR1H
Nuclear Receptor transcription pathway	1	20.0×	0.097	RXRG
mRNA 3’-end processing	1	19.7×	0.097	DDX39B
Chemokine receptors bind chemokines	1	18.7×	0.099	CCRL2
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	15.2×	0.113	DDX39B
Interferon alpha/beta signaling	1	15.2×	0.113	HLA-C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 16 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response	5	14.7×	0.004	TNF, CCRL2, HLA-C, LTB, MICB
positive regulation of translational initiation by iron	1	1053.2×	0.019	TNF
negative regulation of branching involved in lung morphogenesis	1	1053.2×	0.019	TNF
negative regulation of bile acid secretion	1	1053.2×	0.019	TNF
response to Gram-negative bacterium	1	1053.2×	0.019	TNF
positive regulation of interleukin-33 production	1	1053.2×	0.019	TNF
regulation of NAD metabolic process	1	1053.2×	0.019	MACROH2A1
negative regulation of protein localization to chromosome, telomeric region	1	1053.2×	0.019	MACROH2A1
response to 3,3’,5-triiodo-L-thyronine	1	1053.2×	0.019	TNF
negative regulation of tumor necrosis factor (ligand) superfamily member 11 production	1	1053.2×	0.019	LTF
negative regulation of L-glutamate import across plasma membrane	1	526.6×	0.019	TNF
chronic inflammatory response to antigenic stimulus	1	526.6×	0.019	TNF
positive regulation of chronic inflammatory response to antigenic stimulus	1	526.6×	0.019	TNF
positive regulation of fractalkine production	1	526.6×	0.019	TNF
host-mediated suppression of viral proces	1	526.6×	0.019	LTF
positive regulation of protein transport	1	526.6×	0.019	TNF
positive regulation of vitamin D biosynthetic process	1	526.6×	0.019	TNF
negative regulation of cell cycle G2/M phase transition	1	526.6×	0.019	MACROH2A1
regulation of response to oxidative stress	1	526.6×	0.019	MACROH2A1
positive regulation of response to oxidative stress	1	526.6×	0.019	MACROH2A1
response to hydrogen sulfide	1	526.6×	0.019	TNF
response to quercetin	1	526.6×	0.019	TNF
response to gold nanoparticle	1	526.6×	0.019	TNF
positive regulation of blood microparticle formation	1	526.6×	0.019	TNF
regulation of endothelial cell apoptotic process	1	526.6×	0.019	TNF
positive regulation of extrinsic apoptotic signaling pathway	2	56.9×	0.019	TNF, LTB
negative regulation of viral genome replication	2	46.8×	0.019	TNF, LTF
humoral immune response	2	35.1×	0.019	TNF, LTF
killing of cells of another organism	2	34.0×	0.019	LTF, MICB
positive regulation of canonical NF-kappaB signal transduction	3	13.6×	0.019	TNF, LTB, LTF

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Megestrol Acetate	Approved (phase 4)
Abacavir	Phase 3 (in late-stage trials)
Albuvirtide	Phase 3 (in late-stage trials)
Atazanavir	Phase 3 (in late-stage trials)
Cobicistat	Phase 3 (in late-stage trials)
Darunavir	Phase 3 (in late-stage trials)
Didanosine	Phase 3 (in late-stage trials)
Dolutegravir	Phase 3 (in late-stage trials)
Efavirenz	Phase 3 (in late-stage trials)
Elvitegravir	Phase 3 (in late-stage trials)
Emtricitabine	Phase 3 (in late-stage trials)
Enfuvirtide	Phase 3 (in late-stage trials)
Fosamprenavir	Phase 3 (in late-stage trials)
Lamivudine	Phase 3 (in late-stage trials)
Lopinavir	Phase 3 (in late-stage trials)
Maraviroc	Phase 3 (in late-stage trials)
Nelfinavir	Phase 3 (in late-stage trials)
Nevirapine	Phase 3 (in late-stage trials)
OMEGA-3 FATTY ACIDS	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2B	Phase 3 (in late-stage trials)
Raltegravir	Phase 3 (in late-stage trials)
Rilpivirine	Phase 3 (in late-stage trials)
Ritonavir	Phase 3 (in late-stage trials)
Saquinavir	Phase 3 (in late-stage trials)
Stavudine	Phase 3 (in late-stage trials)
Tenofovir Alafenamide	Phase 3 (in late-stage trials)
Tenofovir Anhydrous	Phase 3 (in late-stage trials)
Vicriviroc	Phase 3 (in late-stage trials)
Zidovudine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cannabinol, Chloroquine, Cholecalciferol, Ethambutol, Etonogestrel, Etoposide, Etravirine, Ginseng, American, Isoniazid, Levocarnitine, Lipoic Acid, Alpha, Nogapendekin Alfa, Ofatumumab, Prednisone, Pyrazinamide, Rifampin, Rituximab, Testosterone, Thalidomide.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 17

Druggability breadth: 8 of 19 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
RXRG	BEXAROTENE
TNF	PREDNISOLONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNF	12	4
RXRG	6	4
RPH3AL	0	0
SOX5	0	0
POLR1H	0	0
DDX39B	0	0
PARD3B	0	0
CCRL2	0	0
TGFBRAP1	0	0
RNF39	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEXAROTENE	4	RXRG
OXAPROZIN	4	RXRG
TRETINOIN	4	RXRG
ALITRETINOIN	4	RXRG
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	TNF
LENALIDOMIDE	4	TNF
MARIMASTAT	3	TNF
IBERDOMIDE	3	TNF
PIRINIXIC ACID	2	RXRG
IRX-4204	2	RXRG
DORAMAPIMOD	2	TNF
AVADOMIDE	2	TNF
MIZACORAT	2	TNF
LINPERLISIB	2	TNF
ROLIPRAM	2	TNF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RXRG	193	Binding:169, Functional:24
TNF	193	Binding:162, Functional:31
CCRL2	6	Binding:5, Functional:1
LTF	3	Binding:3
DDX39B	1	Binding:1
DGKI	1	Binding:1
HLA-C	1	Binding:1
LTB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DGKI	2.7.1.107	diacylglycerol kinase (ATP)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RXRG	193
TNF	193

Pharmacogenomics

Cohort genes with a PharmGKB record: 19; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

18 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)
BEXAROTENE	4	RXRG
OXAPROZIN	4	RXRG
TRETINOIN	4	RXRG
ALITRETINOIN	4	RXRG
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	TNF
LENALIDOMIDE	4	TNF
MARIMASTAT	3	TNF
IBERDOMIDE	3	TNF
PIRINIXIC ACID	2	RXRG
IRX-4204	2	RXRG
DORAMAPIMOD	2	TNF
AVADOMIDE	2	TNF
MIZACORAT	2	TNF
LINPERLISIB	2	TNF
ROLIPRAM	2	TNF

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RXRG, TNF
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	HLA-C, MICB
D	Druggable family + AlphaFold only, no drug	2	CCRL2, DGKI
E	Difficult family or no structure, no drug	13	RPH3AL, SOX5, POLR1H, DDX39B, PARD3B, TGFBRAP1, RNF39, MCCD1, CYCSP5, NBPF14 (+3 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RPH3AL	0	—
SOX5	0	—
POLR1H	0	—
DDX39B	1	—
PARD3B	0	—
CCRL2	6	—
TGFBRAP1	0	—
RNF39	0	—
MCCD1	0	—
CYCSP5	0	—
NBPF14	0	—
DGKI	1	—
MACROH2A1	0	—
HLA-C	1	—
LTB	1	—
LTF	3	—
MICB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 706.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	528
PHASE2	43
PHASE4	41
PHASE1	33
PHASE3	30
PHASE1/PHASE2	16
PHASE2/PHASE3	8
EARLY_PHASE1	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00116116	PHASE4	COMPLETED	DART II - A Phase IV Study of 3 Antiretroviral Medicines in Combination, in HIV Patients Who Have Not Been Previously Treated With Antiretroviral Therapy
NCT00124358	PHASE4	UNKNOWN	Buprenorphine and Integrated HIV Care Evaluation
NCT00144352	PHASE4	COMPLETED	In-Vivo Response of P. Falciparum to Antimalarial Treatment in HIV-Infected and HIV-Uninfected Adults
NCT00202228	PHASE4	COMPLETED	Lactate Metabolism Study in HIV Infected Persons
NCT00207168	PHASE4	COMPLETED	To Assess Compliance With a Once-daily Regimen of Lamivudine, Efavirenz and Didanosine
NCT00214435	PHASE4	UNKNOWN	Once Daily 3TC, Efavirenz and ddI for HIV Infection
NCT00268827	PHASE4	COMPLETED	A Comparison Study of Kaletra Soft-Gel Capsules and Kaletra Tablets in an African American Cohort
NCT00317460	PHASE4	COMPLETED	Buprenorphine and Integrated HIV Care
NCT00346697	PHASE4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00367081	PHASE4	COMPLETED	Treatment of Cerebral Toxoplasmosis in HIV/AIDS
NCT00380770	PHASE4	COMPLETED	HIV/AIDS Kaposis Sarcoma: Comparison of Response to HAART vs HAART Plus CXT
NCT00829114	PHASE4	COMPLETED	Interactions Between Antiretrovirals (ARVs) and Combined Oral Contraceptives (COCs)
NCT00853840	PHASE4	COMPLETED	Study To Investigate The Hemodynamic Effects Of Single Dose Vardenafil In Subjects Receiving Maraviroc
NCT00986063	PHASE4	COMPLETED	Genotype Based Personalized Prescription of Nevirapine
NCT01013987	PHASE4	UNKNOWN	Maraviroc (Celsentri) With Raltegravir and Darunavir/Ritonavir for the Treatment of Triple Class Failure in Adult HIV-1 Infected Patients
NCT01025830	PHASE4	COMPLETED	Triomune Bioequivalence With Innovators
NCT01075152	PHASE4	COMPLETED	Cryptococcal Optimal ART Timing Trial
NCT01189695	PHASE4	COMPLETED	Maintenance Boosted Lopinavir Monotherapy Following Salvage Protease-inhibitor (PI) Based Regimen in HIV With Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Based Regimen Failure
NCT01443923	PHASE4	TERMINATED	Boceprevir Drug Combination for Hepatitis C Treatment in People With and Without HIV
NCT01700790	PHASE4	TERMINATED	Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin
NCT01866267	PHASE4	COMPLETED	Switching Undetectables to Selzentry
NCT02167386	PHASE4	COMPLETED	PrEPared and Strong: Clinic-Based PrEP for Black MSM
NCT02477527	PHASE4	COMPLETED	Atripla to Stribild Switch Study to Evaluate Sleep Disturbances
NCT02620150	PHASE4	COMPLETED	SSRI Effects on Depression and Immunity in HIV/AIDS
NCT03120494	PHASE4	UNKNOWN	Evaluating the Feasibility and Acceptability of Implementing a PrEP Program in PR-CoNCRA (San Juan, Puerto Rico)- Part B
NCT03218592	PHASE4	COMPLETED	ENLIGHTEN: Establishing Novel Antiretroviral (ARV) Imaging for Hair to Elucidate Non-Adherence
NCT03302299	PHASE4	COMPLETED	Alcohol Drinkers’ Exposure to Preventive Therapy for TB (ADEPTT)
NCT03549312	PHASE4	UNKNOWN	Switch to Genvoya Followed by HCV Therapy With Epclusa Followed by Simplification of HIV Therapy With Biktarvy in Patients With HIV-HCV Co-Infected Subjects on Opioid Substitution Therapy
NCT03630549	PHASE4	COMPLETED	Village-based vs Clinic-based ART Care - a Cluster Randomized Controlled Trial in Lesotho
NCT03670316	PHASE4	COMPLETED	Effectiveness of a Smoking Cessation Algorithm Integrated Into HIV Primary Care
NCT03838497	PHASE4	COMPLETED	Immunogenicity and Safety of 13-valent Pneumococcal Conjugate Vaccine Among HIV-infected Adults
NCT03842436	PHASE4	COMPLETED	Feasibility and Acceptability of Digital Pills to Monitor PrEP Adherence in MSM With Substance Use
NCT04050540	PHASE4	COMPLETED	Doxycycline PEP for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV PrEP
NCT04183738	PHASE4	WITHDRAWN	Inflammation and Co-Infections in D²EFT
NCT04191278	PHASE4	WITHDRAWN	Mobile Health Interventions for Medication Adherence Among PLWH
NCT04192487	PHASE4	COMPLETED	Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04249037	PHASE4	TERMINATED	Rapid Start vs. Standard Start Antiretroviral Therapy (ART) in HIV
NCT04418037	PHASE4	COMPLETED	DHFS for Medication Adherence Support During Hospital Admissions for Person Living With HIV
NCT04431518	PHASE4	COMPLETED	Pharmacokinetics of JULUCA in Hemodialysis
NCT04754698	PHASE4	COMPLETED	COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DARUNAVIR	4	18
LAMIVUDINE	4	14
MARAVIROC	4	8
EFAVIRENZ	4	5
STAVUDINE	4	4
ABACAVIR	4	3
DOLUTEGRAVIR	4	3
DOXYCYCLINE ANHYDROUS	4	3
EMTRICITABINE	4	3
LOPINAVIR	4	3
NEVIRAPINE	4	3
RILPIVIRINE	4	3
BICTEGRAVIR	4	2
COBICISTAT	4	2
ENFUVIRTIDE	4	2
ETRAVIRINE	4	2
RALTEGRAVIR	4	2
RITONAVIR	4	2
VARENICLINE	4	2
BOCEPREVIR	4	1
BUPRENORPHINE	4	1
CHLOROQUINE	4	1
DEXAMETHASONE	4	1
DIDANOSINE	4	1
ETHINYL ESTRADIOL	4	1
ETONOGESTREL	4	1
LEVOCARNITINE	4	1
LISINOPRIL	4	1
LISINOPRIL ANHYDROUS	4	1
NAPROXEN	4	1