Human papilloma virus infection

Summary

Human papilloma virus infection (MONDO:0005161) is a disease with 14 cohort genes (104 GWAS associations across 8 studies) and 169 clinical trials. Top therapeutic interventions include human papillomavirus, l1 protein virus like particles, diphtheria toxoid, and hydroxyurea.

At a glance

• Cohort genes: 14
• GWAS associations: 104
• Clinical trials: 169

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	human papilloma virus infection
Mondo ID	MONDO:0005161
EFO	EFO:0001668
MeSH	D030361
DOID	DOID:11166
NCIT	C27851
SNOMED CT	240532009
UMLS	C0343641
MedGen	87475
Is cancer (heuristic)	no

Also known as: Human papilloma Virus infection · Human papillomavirus caused disease or disorder · Human papillomavirus disease or disorder · Human Papillomavirus infection

Data availability: 104 GWAS associations (8 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › viral infectious disease › primary viral infectious disease › human papilloma virus infection

Related subtypes (31): plantar wart, monkeypox, smallpox, rubella, Rotavirus infection, Arenaviridae infectious disease, Astroviridae infectious disease, Caliciviridae infectious disease, cowpox, Flaviviridae infectious disease, Hepadnaviridae infectious disease, Herpesviridae infectious disease, influenza, Mononegavirales infectious disease, Nidovirales infectious disease, phlebotomus fever, Picornaviridae infectious disease, polyomavirus infectious disease, Togaviridae infectious disease, viral encephalitis, viral hepatitis, viral pneumonia, viral exanthem, deltaretrovirus infections, Bunyaviridae infectious disease, viral sexually transmitted disease, lentivirus infection, viral myocarditis, viral pericarditis, adenoviridae infectious disease, aleutian mink disease, human

Subtypes (1): anogenital human papillomavirus infection

Genetics & variants

GWAS landscape

104 GWAS associations across 8 studies. Top hits map to 31 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9266329	1e-12	HLA-B	A	0.61
rs28418426	8e-12	HLA-DQA1 - HLA-DQB1	C	1.56
rs35189640	1e-09	ABTB3	T	2.75
rs2523679	3e-09	HCP5	T	0.51
rs3828805	3e-09	HLA-DQB1	C	1.3
rs10851478	1e-08	FAM227B	A	1.22
rs2342234	1e-08	PARP4P2	?
rs116471799	2e-08	ZEB2P1 - LDB2	?
rs116054643	3e-08	PPP3CA	?
rs1229984	4e-08	ADH1B	G	0.59
rs138289957	4e-08	LINC02946 - NCK2	?
rs13407090	4e-08	LINC02946 - NCK2	?
rs75543399	4e-08	LINC02946 - NCK2	?
rs2152687	4e-08	PARP4P2, CCNQP3	?
rs10462706	5e-08	CLPTM1L	T	0.76
rs201982221	5e-08	LHPP	?	1.74
rs692309	5e-08	DTWD1 - ATP8B4	C	0.82
rs1879062	5e-08	CDH12 - Y_RNA	?
rs1028206	6e-08	CDH12 - Y_RNA	?
chr5:10847898	7e-08		?	6.87
rs4654837	9e-08	HTR1D - RPL29P6	?
rs9836282	1e-07	CBX1P5 - PPIAP74	C	0.75
rs1516535	1e-07	TENM3	C	1.43
rs3823363	1e-07	POLR1HASP, POLR1HASP, HCG9	A	0.82
rs8181047	1e-07	CDKN2B-AS1	G	1.22
rs73784569	1e-07	PACRG	?
rs10180404	1e-07	ACYP2	?
rs143668247	2e-07	LINC02789 - RNU6-778P	?	3.66
rs729353	2e-07	MAT2B - RNU6-168P	A	1.4
rs55864736	2e-07	MYO16	A	1.45

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90085701	Ferreiro-Iglesias A	2021	2,359	0	Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
GCST90085699	Ferreiro-Iglesias A	2021	1,078	5,256	Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
GCST90492710	Adebamowo SN	2024	903	9,846	Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections.
GCST90492711	Adebamowo SN	2024	903	9,846	Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections.
GCST90085700	Ferreiro-Iglesias A	2021	565	5,256	Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
GCST011837	Adebamowo SN	2020	125	0	Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.
GCST011836	Adebamowo SN	2020	51	0	Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.
GCST011620	Joo J	2019	0	0	The association of integration patterns of human papilloma virus and single nucleotide polymorphisms on immune- or DNA repair-related genes in cervical cancer patients.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	15
non_coding_transcript_exon_variant	3
regulatory_region_variant	1
missense_variant	1
unknown	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9266329	6	31363011	G>A	0.05	non_coding_transcript_exon_variant	HLA-B	1e-12	Tier 4: intronic/intergenic
rs28418426	6	32651877	T>C	0.05	intergenic_variant	HLA-DQA1 - HLA-DQB1	8e-12	Tier 4: intronic/intergenic
rs35189640	12	107582831	C>T	0.05	intron_variant	ABTB3	1e-09	Tier 4: intronic/intergenic
rs2523679	6	31466557	C>G,T	0.05	intron_variant	HCP5	3e-09	Tier 4: intronic/intergenic
rs3828805	6	32668343	T>A,C,G	0.05	regulatory_region_variant	HLA-DQB1	3e-09	Tier 3: regulatory
rs10851478	15	49536822	T>C	0.05	intron_variant	FAM227B	1e-08	Tier 4: intronic/intergenic
rs2342234	13	19385993	T>A,C,G		non_coding_transcript_exon_variant	PARP4P2	1e-08	Tier 4: intronic/intergenic
rs116471799	4	16424409	G>A,C		intron_variant	ZEB2P1 - LDB2	2e-08	Tier 4: intronic/intergenic
rs116054643	4	101300926	G>A,T	0.05	intron_variant	PPP3CA	3e-08	Tier 4: intronic/intergenic
rs1229984	4	99318162	T>A,C,G	0.05	missense_variant	ADH1B	4e-08	Tier 1: coding
rs138289957	2	105685243	T>A		intron_variant	LINC02946 - NCK2	4e-08	Tier 4: intronic/intergenic
rs13407090	2	105690494	C>A		intron_variant	LINC02946 - NCK2	4e-08	Tier 4: intronic/intergenic
rs75543399	2	105670030	G>A		intron_variant	LINC02946 - NCK2	4e-08	Tier 4: intronic/intergenic
rs2152687	13	19382475	C>G,T		non_coding_transcript_exon_variant	PARP4P2, CCNQP3	4e-08	Tier 4: intronic/intergenic
rs10462706	5	1343679	C>G,T	0.05	intron_variant	CLPTM1L	5e-08	Tier 4: intronic/intergenic
rs201982221	10	124468877	CCAG>C		intron_variant	LHPP	5e-08	Tier 4: intronic/intergenic
rs692309	15	49706485	T>A,C	0.05	intergenic_variant	DTWD1 - ATP8B4	5e-08	Tier 4: intronic/intergenic
rs1879062	5	23044423	A>G	0.05	intergenic_variant	CDH12 - Y_RNA	5e-08	Tier 4: intronic/intergenic
rs1028206	5	23046022	A>C,G,T	0.05	intergenic_variant	CDH12 - Y_RNA	6e-08	Tier 4: intronic/intergenic
chr5:10847898							7e-08	Tier 4: intronic/intergenic
rs4654837	1	23233507	T>A,C,G	0.05	intergenic_variant	HTR1D - RPL29P6	9e-08	Tier 4: intronic/intergenic
rs9836282	3	167024803	T>C	0.05	intergenic_variant	CBX1P5 - PPIAP74	1e-07	Tier 4: intronic/intergenic
rs1516535	4	182334536	G>C	0.05	intron_variant	TENM3	1e-07	Tier 4: intronic/intergenic
rs3823363	6	29975938	C>T	0.05	intron_variant	POLR1HASP, POLR1HASP, HCG9	1e-07	Tier 4: intronic/intergenic
rs8181047	9	22064466	A>C,G,T	0.05	intron_variant	CDKN2B-AS1	1e-07	Tier 4: intronic/intergenic
rs73784569	6	163291426	C>T		intron_variant	PACRG	1e-07	Tier 4: intronic/intergenic
rs10180404	2	54218617	C>T	0.05	intron_variant	ACYP2	1e-07	Tier 4: intronic/intergenic
rs143668247	1	199732754	C>A,G	0.05	intergenic_variant	LINC02789 - RNU6-778P	2e-07	Tier 4: intronic/intergenic
rs729353	5	163522414	T>A,C,G	0.05	intergenic_variant	MAT2B - RNU6-168P	2e-07	Tier 4: intronic/intergenic
rs55864736	13	109162764	G>A	0.05	intron_variant	MYO16	2e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TIAM1	Orphanet:528084	Non-specific syndromic intellectual disability
JPH2	Orphanet:154	Familial isolated dilated cardiomyopathy
VSX2	Orphanet:98938	Colobomatous microphthalmia

Cohort genes → proteins

14 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPS6KA4	HGNC:10433	ENSG00000162302	O75676	Ribosomal protein S6 kinase alpha-4	gwas
TIAM1	HGNC:11805	ENSG00000156299	Q13009	Rho guanine nucleotide exchange factor TIAM1	gwas
JPH2	HGNC:14202	ENSG00000149596	Q9BR39	Junctophilin-2	gwas
NEGR1	HGNC:17302	ENSG00000172260	Q7Z3B1	Neuronal growth regulator 1	gwas
VSX2	HGNC:1975	ENSG00000119614	P58304	Visual system homeobox 2	gwas
IFTAP	HGNC:25142	ENSG00000166352	Q86VG3	Intraflagellar transport-associated protein	gwas
UBE2W	HGNC:25616	ENSG00000104343	Q96B02	Ubiquitin-conjugating enzyme E2 W	gwas
DAP	HGNC:2672	ENSG00000112977	P51397	Death-associated protein 1	gwas
MIR646HG	HGNC:27659	ENSG00000228340		MIR646 host gene	gwas
MIR365B	HGNC:33693	ENSG00000283978		microRNA 365b	gwas
LINC00290	HGNC:38515	ENSG00000248197		long intergenic non-protein coding RNA 290	gwas
KLF12	HGNC:6346	ENSG00000118922	Q9Y4X4	Krueppel-like factor 12	gwas
NR5A2	HGNC:7984	ENSG00000116833	O00482	Nuclear receptor subfamily 5 group A member 2	gwas
PAFAH2	HGNC:8579	ENSG00000158006	Q99487	Platelet-activating factor acetylhydrolase 2, cytoplasmic	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS6KA4	Ribosomal protein S6 kinase alpha-4	Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation…
TIAM1	Rho guanine nucleotide exchange factor TIAM1	Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities.
JPH2	Junctophilin-2	Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes.
NEGR1	Neuronal growth regulator 1	May be involved in cell-adhesion.
VSX2	Visual system homeobox 2	Acts as a transcriptional regulator through binding to DNA at the consensus sequence 5’-[TC]TAATT[AG][AG]-3’ upstream of gene promoters.
IFTAP	Intraflagellar transport-associated protein	Seems to play a role in ciliary BBSome localization, maybe through interaction with IFT-A complex.
UBE2W	Ubiquitin-conjugating enzyme E2 W	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
DAP	Death-associated protein 1	Ribosome-binding protein involved in ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation.
KLF12	Krueppel-like factor 12	Confers strong transcriptional repression to the AP-2-alpha gene.
NR5A2	Nuclear receptor subfamily 5 group A member 2	Orphan nuclear receptor that binds DNA as a monomer to the 5’-TCAAGGCCA-3’ sequence and controls expression of target genes: regulates key biological processes, such as early embryonic development, cholesterol and bile acid synthesis pathw…
PAFAH2	Platelet-activating factor acetylhydrolase 2, cytoplasmic	Catalyzes the hydrolyze of the acetyl group at the sn-2 position of platelet-activating factor (PAF) and its analogs, leading to their inactivation.

Protein-family classification

Druggable: 5 · Difficult: 3 · Unknown: 6 · Druggable fraction: 0.36

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	27.6×	0.250
Antibody/Immunoglobulin	1	2.1×	0.660
Kinase	1	2.0×	0.660
Enzyme (other)	2	1.7×	0.660
Scaffold/PPI	1	1.2×	0.660
Transcription factor	2	1.2×	0.660
Other/Unknown	6	0.8×	0.893

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS6KA4	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
TIAM1	Scaffold/PPI	no		DH_dom, GDS_CDC24_CS, PDZ
JPH2	Other/Unknown	no		MORN, Junctophilin
NEGR1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
VSX2	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
IFTAP	Other/Unknown	no		IFTAP
UBE2W	Enzyme (other)	yes	2.3.2.24	UBC, UBQ-conjugating_enzyme/RWD, Ub_conjugating_enzyme-E2-like
DAP	Other/Unknown	no		DAP1/DAPL1
MIR646HG	Other/Unknown	no
MIR365B	Other/Unknown	no
LINC00290	Other/Unknown	no
KLF12	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
NR5A2	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
PAFAH2	Enzyme (other)	yes	3.1.1.47	PAF_acetylhydro_eukaryote, AB_hydrolase_fold

Expression context

Cohort genes with no expression data: 0.

11 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	3
oocyte	2
secondary oocyte	2
left ventricle myocardium	2
islet of Langerhans	2
pancreas	2
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
cerebellar vermis	1
skeletal muscle tissue of rectus abdominis	1
tibialis anterior	1
Brodmann (1909) area 23	1
Brodmann (1909) area 46	1
occipital lobe	1
cortical plate	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
bronchial epithelial cell	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS6KA4	215	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
TIAM1	280	ubiquitous	marker	cerebellar vermis, oocyte, secondary oocyte
JPH2	173	broad	yes	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, tibialis anterior
NEGR1	242	broad	marker	Brodmann (1909) area 46, Brodmann (1909) area 23, occipital lobe
VSX2	11	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, cortical plate
IFTAP	247	ubiquitous	marker	left ventricle myocardium, bronchial epithelial cell, myocardium
UBE2W	269	ubiquitous	marker	oocyte, endothelial cell, secondary oocyte
DAP	252	ubiquitous	marker	body of pancreas, stromal cell of endometrium, islet of Langerhans
MIR646HG	183	broad	marker	buccal mucosa cell, thymus, sperm
MIR365B	43		yes	kidney, monocyte, blood
LINC00290	66		yes	adrenal tissue, caudate nucleus, nucleus accumbens
KLF12	267	ubiquitous	marker	corpus epididymis, superficial temporal artery, pigmented layer of retina
NR5A2	159	broad	marker	body of pancreas, pancreas, islet of Langerhans
PAFAH2	210	ubiquitous	marker	body of pancreas, colonic epithelium, pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TIAM1	2,688
UBE2W	2,199
NEGR1	1,895
NR5A2	1,829
VSX2	1,484
RPS6KA4	1,369
KLF12	1,346
JPH2	1,278
PAFAH2	748
DAP	531

Structural data

PDB: 5 · AlphaFold-only: 6 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NR5A2	O00482	28
TIAM1	Q13009	10
UBE2W	Q96B02	3
JPH2	Q9BR39	2
NEGR1	Q7Z3B1	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PAFAH2	Q99487	91.31
RPS6KA4	O75676	72.00
DAP	P51397	68.92
IFTAP	Q86VG3	66.65
VSX2	P58304	61.65
KLF12	Q9Y4X4	51.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 14 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activated NTRK2 signals through CDK5	1	317.2×	0.056	TIAM1
Signaling by NTRK2 (TRKB)	1	271.9×	0.056	TIAM1
Regulation of gene expression in early pancreatic precursor cells	1	237.9×	0.056	NR5A2
Axon guidance	2	15.1×	0.061	RPS6KA4, TIAM1
Nervous system development	2	14.3×	0.061	RPS6KA4, TIAM1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	82.8×	0.075	TIAM1
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	1	61.4×	0.075	UBE2W
SUMOylation of intracellular receptors	1	56.0×	0.075	NR5A2
Platelet homeostasis	1	46.4×	0.075	PAFAH2
EPHB-mediated forward signaling	1	44.3×	0.075	TIAM1
Recycling pathway of L1	1	37.3×	0.075	RPS6KA4
Cell death signalling via NRAGE, NRIF and NADE	1	36.6×	0.075	TIAM1
EPH-ephrin mediated repulsion of cells	1	36.6×	0.075	TIAM1
Nuclear Receptor transcription pathway	1	33.4×	0.075	NR5A2
p75 NTR receptor-mediated signalling	1	31.2×	0.075	TIAM1
NRAGE signals death through JNK	1	30.7×	0.075	TIAM1
Signaling by NTRKs	1	30.2×	0.075	TIAM1
Post-translational modification: synthesis of GPI-anchored proteins	1	28.0×	0.075	NEGR1
EPH-Ephrin signaling	1	27.6×	0.075	TIAM1
Death Receptor Signaling	1	23.2×	0.082	TIAM1
G alpha (12/13) signalling events	1	22.9×	0.082	TIAM1
RAC2 GTPase cycle	1	21.1×	0.082	TIAM1
L1CAM interactions	1	20.0×	0.082	RPS6KA4
RAC3 GTPase cycle	1	19.8×	0.082	TIAM1
Developmental Biology	2	4.8×	0.095	RPS6KA4, TIAM1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	13.8×	0.108	NR5A2
Estrogen-dependent gene expression	1	12.6×	0.111	NR5A2
RHOA GTPase cycle	1	12.4×	0.111	TIAM1
CDC42 GTPase cycle	1	12.1×	0.111	TIAM1
RAC1 GTPase cycle	1	10.2×	0.124	TIAM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of glucocorticoid biosynthetic process	1	1532.0×	0.017	NR5A2
regulation of cardiac muscle tissue development	1	1532.0×	0.017	JPH2
obsolete positive regulation of ryanodine-sensitive calcium-release channel activity	1	1532.0×	0.017	JPH2
zygotic genome activation	1	1532.0×	0.017	NR5A2
primary ovarian follicle growth	1	766.0×	0.021	NR5A2
positive regulation of tendon cell differentiation	1	766.0×	0.021	NR5A2
positive regulation of saliva secretion	1	510.7×	0.021	NEGR1
pancreas morphogenesis	1	510.7×	0.021	NR5A2
morula formation	1	510.7×	0.021	NR5A2
regulation of dopaminergic neuron differentiation	1	510.7×	0.021	TIAM1
cholesterol homeostasis	2	28.4×	0.021	NEGR1, NR5A2
protein localization to plasma membrane raft	1	383.0×	0.021	NEGR1
ribosome hibernation	1	383.0×	0.021	DAP
acinar cell differentiation	1	306.4×	0.025	NR5A2
inner cell mass cell differentiation	1	255.3×	0.025	NR5A2
positive regulation of T cell anergy	1	255.3×	0.025	NR5A2
retinal bipolar neuron differentiation	1	255.3×	0.025	VSX2
negative regulation of synapse assembly	1	218.9×	0.026	NEGR1
positive regulation of transcription by RNA polymerase II	4	5.4×	0.026	RPS6KA4, VSX2, KLF12, NR5A2
skeletal muscle organ development	1	191.5×	0.027	NEGR1
tissue development	1	170.2×	0.027	NR5A2
exocrine pancreas development	1	153.2×	0.027	NR5A2
obsolete positive regulation of CREB transcription factor activity	1	153.2×	0.027	RPS6KA4
embryonic cleavage	1	153.2×	0.027	NR5A2
homeostatic process	1	153.2×	0.027	NR5A2
negative regulation of glial cell proliferation	1	153.2×	0.027	NEGR1
regulation of epithelial to mesenchymal transition	1	139.3×	0.027	TIAM1
calcineurin-mediated signaling	1	139.3×	0.027	NR5A2
cellular response to misfolded protein	1	127.7×	0.029	UBE2W
regulation of cardiac muscle contraction by calcium ion signaling	1	117.8×	0.029	JPH2

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
HUMAN PAPILLOMAVIRUS, L1 PROTEIN VIRUS LIKE PARTICLES	Approved (phase 4)
Imiquimod	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Balstilimab, Hepatitis B Virus Vaccine Inactivated, INTERFERON ALFA-2B, Infigratinib.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 13

Druggability breadth: 3 of 14 evidence-associated genes (21%) 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
RPS6KA4	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS6KA4	34	4
TIAM1	0	0
JPH2	0	0
NEGR1	0	0
VSX2	0	0
IFTAP	0	0
UBE2W	0	0
DAP	0	0
MIR646HG	0	0
MIR365B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	RPS6KA4
RUXOLITINIB	4	RPS6KA4
NINTEDANIB	4	RPS6KA4
SUNITINIB	4	RPS6KA4
ERLOTINIB	4	RPS6KA4
MIDOSTAURIN	4	RPS6KA4
GEFITINIB	4	RPS6KA4
LINIFANIB	3	RPS6KA4
ORANTINIB	3	RPS6KA4
ENZASTAURIN	3	RPS6KA4
ALVOCIDIB	3	RPS6KA4
DOVITINIB	3	RPS6KA4
LESTAURTINIB	3	RPS6KA4
RUBOXISTAURIN	3	RPS6KA4
PAMAPIMOD	2	RPS6KA4
SU-014813	2	RPS6KA4
REBASTINIB	2	RPS6KA4
SCH-900776	2	RPS6KA4
R-406	2	RPS6KA4
AT-9283	2	RPS6KA4
BI-2536	2	RPS6KA4
R-1487	1	RPS6KA4
GSK-461364	1	RPS6KA4
KW-2449	1	RPS6KA4
AZD-7762	1	RPS6KA4
AMG-900	1	RPS6KA4
PF-03758309	1	RPS6KA4
TAK-901	1	RPS6KA4
GSK-1059615	1	RPS6KA4
PF-03814735	1	RPS6KA4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
RPS6KA4	389	Binding:387, Functional:1, ADMET:1
NR5A2	254	Binding:243, Functional:11
TIAM1	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UBE2W	2.3.2.24, 2.3.2.25	(E3-independent) E2 ubiquitin-conjugating enzyme, N-terminal E2 ubiquitin-conjugating enzyme
PAFAH2	3.1.1.47	1-alkyl-2-acetylglycerophosphocholine esterase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RPS6KA4	389
NR5A2	254

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.

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

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)
FEDRATINIB	4	RPS6KA4
RUXOLITINIB	4	RPS6KA4
NINTEDANIB	4	RPS6KA4
SUNITINIB	4	RPS6KA4
ERLOTINIB	4	RPS6KA4
MIDOSTAURIN	4	RPS6KA4
GEFITINIB	4	RPS6KA4
LINIFANIB	3	RPS6KA4
ORANTINIB	3	RPS6KA4
ENZASTAURIN	3	RPS6KA4
ALVOCIDIB	3	RPS6KA4
DOVITINIB	3	RPS6KA4
LESTAURTINIB	3	RPS6KA4
RUBOXISTAURIN	3	RPS6KA4
PAMAPIMOD	2	RPS6KA4
SU-014813	2	RPS6KA4
REBASTINIB	2	RPS6KA4
SCH-900776	2	RPS6KA4
R-406	2	RPS6KA4
AT-9283	2	RPS6KA4
BI-2536	2	RPS6KA4
R-1487	1	RPS6KA4
GSK-461364	1	RPS6KA4
KW-2449	1	RPS6KA4
AZD-7762	1	RPS6KA4
AMG-900	1	RPS6KA4
PF-03758309	1	RPS6KA4
TAK-901	1	RPS6KA4
GSK-1059615	1	RPS6KA4
PF-03814735	1	RPS6KA4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPS6KA4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	NEGR1, UBE2W, NR5A2
D	Druggable family + AlphaFold only, no drug	1	PAFAH2
E	Difficult family or no structure, no drug	9	TIAM1, JPH2, VSX2, IFTAP, DAP, MIR646HG, MIR365B, LINC00290, KLF12

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NR5A2	254	—
TIAM1	5	—
JPH2	0	—
NEGR1	0	—
VSX2	0	—
IFTAP	0	—
UBE2W	0	—
DAP	0	—
MIR646HG	0	—
MIR365B	0	—
LINC00290	0	—
KLF12	0	—
PAFAH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 169.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	115
PHASE2	17
PHASE3	16
PHASE4	8
PHASE1	4
PHASE2/PHASE3	3
PHASE1/PHASE2	3
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03180034	PHASE4	ACTIVE_NOT_RECRUITING	Comparing One or Two Doses of the Human Papillomavirus Vaccine for the Prevention of Human Papillomavirus Infection, ESCUDDO Study
NCT00925288	PHASE4	COMPLETED	Acceptability of Human Papillomavirus (HPV) Vaccine in Female Sex Workers
NCT01082861	PHASE4	TERMINATED	Efficacy and Immunomodulation Study of Simultaneous Human Papillomavirus/ Hepatitis B (HPV/HBV) Vaccination
NCT01824537	PHASE4	COMPLETED	Transmission Reduction and Prevention With HPV Vaccination (TRAP-HPV) Study
NCT04474821	PHASE4	COMPLETED	HPV Educational Intervention to Increase Acceptance and Completion of Free HPV Vaccination Among Underserved Adults
NCT05279248	PHASE4	UNKNOWN	The Immunogenicity and Safety of the Vaccination of Human Papillomavirus Vaccine and Measles-Mumps-Rubella Vaccine
NCT05415345	PHASE4	UNKNOWN	Immunogenicity and Safety of Co-immunization With Cecolin and Hecolin
NCT05439083	PHASE4	UNKNOWN	Immunogenicity of 9-valent HPV Vaccine
NCT05662020	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Immunogenicity and Safety of HPV Vaccine in Healthy Female Participants Aged 9-26 Years in China
NCT06281119	PHASE3	NOT_YET_RECRUITING	Clinical Study to Evaluate SIIPL QHPV Vaccine (CERVAVAC®) in Women Living with HIV Aged 15-25 Years
NCT06632912	PHASE3	ACTIVE_NOT_RECRUITING	Phase IIIb Clinical Trial of Quadrivalent Recombinant Human Papillomavirus Vaccine (Hansenulapolymorpha) for Age/Immunization Schedule Bridging
NCT00481767	PHASE3	COMPLETED	Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals’ Human Papillomavirus (HPV) Vaccine (GSK580299) in Healthy Female Subjects 10-25 Years of Age.
NCT00518180	PHASE3	COMPLETED	A Study to Evaluate Safety and Immune Response of Novartis Meningococcal ACWY Conjugate Vaccine In Adolescents
NCT00543543	PHASE3	COMPLETED	Broad Spectrum HPV (Human Papillomavirus) Vaccine Study in 16-to 26-Year-Old Women (V503-001)
NCT00973362	PHASE3	COMPLETED	Clinical Evaluation of the APTIMA® HPV Assay Using the TIGRIS® System
NCT00988884	PHASE3	COMPLETED	A Study of V503 Given Concomitantly With Menactra™ and Adacel™ in 11 to 15 Year Olds (V503-005)
NCT01095198	PHASE2/PHASE3	UNKNOWN	Randomized Trial of Vaginal Self Sampling for Human Papillomavirus (HPV)
NCT01984697	PHASE3	COMPLETED	A Phase III Study of a 2-dose Regimen of a Multivalent Human Papillomavirus (HPV) Vaccine (V503), Administered to 9 to 14 Year-olds and Compared to Young Women, 16 to 26 Years Old (V503-010)
NCT02009800	PHASE3	COMPLETED	ICI-VPH: Impact of HPV Immunisation Schedules Against HPV
NCT02135419	PHASE3	COMPLETED	Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions
NCT02354144	PHASE2/PHASE3	TERMINATED	Lubricant Investigation in Men to Inhibit Transmission of HPV Infection
NCT02733068	PHASE3	COMPLETED	A Phase III Study of Human Papillomavirus (HPV)-16/18 Vaccine.
NCT03158220	PHASE3	COMPLETED	Immunogenicity and Tolerability of Broad Spectrum Human Papillomavirus (HPV) Vaccine in Adult and Young Adult Women (V503-004)
NCT05156541	PHASE3	COMPLETED	Study of the Efficacy and Safety of the Drug Ingaron (Interferon-gamma) in the Treatment of Anogenital Warts
NCT05316064	PHASE2/PHASE3	WITHDRAWN	Reducing Abundance of Human Papilloma Virus in Women by Taking Probiotic
NCT05668572	PHASE3	UNKNOWN	A Phase III Trial Evaluates the Efficacy, Immunogenicity and Safety Profile of HPV Vaccine
NCT06207175	PHASE3	UNKNOWN	A Study to Evaluate the Immunogenicity and Safety of Nonavalent Human Papillomavirus (HPV) Vaccine
NCT01898494	PHASE2	ACTIVE_NOT_RECRUITING	Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer
NCT03036930	PHASE2	ACTIVE_NOT_RECRUITING	Preventive Human Papillomavirus (HPV) Vaccine Trial in Kidney Transplant Recipients
NCT06491446	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Evaluating Clearance of High-Risk HPV and Safety After Administration of ABI-2280 Vaginal Inserts
NCT06705322	PHASE2	NOT_YET_RECRUITING	Cnidium Monnieri Detoxification Formula for Persistent High-risk Human Papillomavirus Infection of Cervix.
NCT07407569	PHASE2	RECRUITING	Developing a First-void Urine-based Infection Model to Study HPV-specific Antibody-virion Interaction Before and After HPV Vaccination
NCT07454915	PHASE2	RECRUITING	PVX4 for the Treatment of Human Papilloma Virus (HPV)16+ Cervical Dysplasia
NCT00054041	PHASE2	COMPLETED	Vaccine Therapy in Preventing Cervical Cancer in Patients With Cervical Intraepithelial Neoplasia
NCT00303823	PHASE2	COMPLETED	Green Tea Extract in Preventing Cervical Cancer in Patients With Human Papillomavirus and Low-Grade Cervical Intraepithelial Neoplasia
NCT00520598	PHASE2	COMPLETED	Broad Spectrum HPV (Human Papillomavirus) Vaccine in 16 to 26 Year Old Women (V505-001)
NCT00551187	PHASE2	COMPLETED	A Study to Evaluate Tolerability and Immunogenicity of V504 Administered Concomitantly With GARDASIL (V504-001)(COMPLETED)
NCT01532102	PHASE1/PHASE2	COMPLETED	Safety and Efficacy Study of Topical AP611074 Gel to Treat Genital Warts
NCT01693783	PHASE2	COMPLETED	Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer
NCT01932697	PHASE2	COMPLETED	Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HUMAN PAPILLOMAVIRUS, L1 PROTEIN VIRUS LIKE PARTICLES	4	7
DIPHTHERIA TOXOID	4	1
HYDROXYUREA	4	1
IMIQUIMOD	4	1
INFIGRATINIB	4	1
TETANUS TOXOID	4	1
VERPASEP CALTESPEN	2	1