hepatitis C virus infection

Summary

hepatitis C virus infection (MONDO:0005231) is a disease with 20 cohort genes (42 GWAS associations across 27 studies) and 590 clinical trials. Top therapeutic interventions include ribavirin, paritaprevir, and ombitasvir.

At a glance

• Cohort genes: 20
• GWAS associations: 42
• Clinical trials: 590

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hepatitis C virus infection
Mondo ID	MONDO:0005231
EFO	EFO:0003047
MeSH	D006526
DOID	DOID:1883
NCIT	C3098
SNOMED CT	128302006
UMLS	C0019196
MedGen	42425
Is cancer (heuristic)	no

Also known as: chronic hepatitis C · hepatitis C infection · Hepatitis C virus caused hepatitis · Hepatitis C virus hepatitis · hepatitis type C · NANBH · non-A, non-B Hepatitis

Data availability: 42 GWAS associations (27 studies) · 164 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › liver disorder › hepatitis › viral hepatitis › hepatitis C virus infection

Related subtypes (5): Epstein-Barr virus hepatitis, hepatitis B virus infection, hepatitis E virus infection, hepatitis D virus infection, hepatitis A virus infection

Subtypes (2): chronic hepatitis C virus infection, acute hepatitis C virus infection

Genetics & variants

GWAS landscape

42 GWAS associations across 27 studies. Top hits map to 16 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs74597329	6e-50	IFNL4	T	2.14
chr19:39739129	7e-24		C	2.78
rs2647006	1e-21	HLA-DQB1 - MTCO3P1	C	1.79
rs778086851	5e-21	IFNL4	CT	2.5
rs2858320	2e-12	HLA-DQB1 - MTCO3P1	G	1.96
chr11:112851068	7e-12		C	0.07
chr19:39730301	8e-12		T	0.08
rs2858317	1e-11	HLA-DQB1 - MTCO3P1	A	1.73
rs4374383	1e-09	MERTK	A
rs2647051	1e-09	HLA-DQB1 - MTCO3P1	C	1.79
rs16851720	9e-09	RNF7	C
rs7251836	4e-08	NLRP13	?
rs75125828	8e-08	CCL1 - TMEM132E-DT	A	1.71
rs73015007	9e-08	SMARCA4	A	1.88
rs2629751	1e-07	GLT8D2	G
rs145242146	1e-07	GPR20 - ASTILCS	A	1.57
rs34437832	1e-07	EIF3A	C	1.41
rs1754257	2e-07	GPR158	A	1.55
rs76398191	2e-07	AIFM1P1 - MALRD1	C	0.69
rs10456404	2e-07	NOTCH4 - TSBP1-AS1	C	1.89
rs62577031	2e-07	PPP1R26-AS1	G	1.57
rs9380516	5e-07	LINC03135	T
rs28368843	5e-07	HLA-DRB9 - HLA-DRB5	T	2.38
rs6087561	6e-07	ASIP	C	1.6
rs1346763	9e-07	DPP10	T	1.4
rs1649709	9e-07	RN7SL292P - SGO1P2	G	1.62
rs7262634	1e-06	EYA2 - ZMYND8	?	25
rs2978048	1e-06	ST3GAL1-DT - LINC03024	?	0.25
kgp3085785	1e-06		?	0.36
rs883924	2e-06	LINC01508	A

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475553	Verma A	2024	19,171	428,932	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477058	Verma A	2024	13,231	107,393	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480958	Verma A	2024	13,231	107,393	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651639	Liu TY	2025	4,229	190,942	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90477057	Verma A	2024	3,828	55,509	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90225539	Jiang L	2022	1,260	6,300	Genome-wide association analyses of common infections in a large practice-based biobank.
GCST007631	Vergara C	2018	701	1,035	Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.
GCST007633	Vergara C	2018	701	1,035	Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.
GCST007632	Vergara C	2018	445	1,756	Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.
GCST90435528	Zhou W	2018	255	403,316	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	0
Tier 3: regulatory	3
Tier 4: intronic/intergenic	34

MAF distribution

Bucket	Variants
common (>=0.05)	30
low_freq (0.01-0.05)	5
rare (<0.01)	0
unknown	4

Functional consequences

Consequence	Count
intron_variant	16
intergenic_variant	10
unknown	7
regulatory_region_variant	3
missense_variant	1
inframe_deletion	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs74597329	19	39248515	T>A,C,G	0.37	missense_variant	IFNL4	6e-50	Tier 1: coding
chr19:39739129				0.2			7e-24	Tier 4: intronic/intergenic
rs2647006	6	32692805	A>C,G,T	0.38	intergenic_variant	HLA-DQB1 - MTCO3P1	1e-21	Tier 4: intronic/intergenic
rs778086851	19	39248513	CCTT>C	0.49	inframe_deletion	IFNL4	5e-21	Tier 1: coding
rs2858320	6	32693516	A>C,G,T	0.42	intergenic_variant	HLA-DQB1 - MTCO3P1	2e-12	Tier 4: intronic/intergenic
chr11:112851068				0.393			7e-12	Tier 4: intronic/intergenic
chr19:39730301				0.313			8e-12	Tier 4: intronic/intergenic
rs2858317	6	32694503	C>A,T	0.37	intergenic_variant	HLA-DQB1 - MTCO3P1	1e-11	Tier 4: intronic/intergenic
rs4374383	2	112013193	A>G	0.42	intron_variant	MERTK	1e-09	Tier 4: intronic/intergenic
rs2647051	6	32703120	T>A,C,G	0.36	intergenic_variant	HLA-DQB1 - MTCO3P1	1e-09	Tier 4: intronic/intergenic
rs16851720	3	141744456	A>C	0.19	intron_variant	RNF7	9e-09	Tier 4: intronic/intergenic
rs7251836	19	55904172	A>G	0.05	intron_variant	NLRP13	4e-08	Tier 4: intronic/intergenic
rs75125828	17	34427369	G>A	0.019	intergenic_variant	CCL1 - TMEM132E-DT	8e-08	Tier 4: intronic/intergenic
rs73015007	19	11073161	G>A	0.014	intergenic_variant	SMARCA4	9e-08	Tier 4: intronic/intergenic
rs2629751	12	104028030	A>G	0.31	intron_variant	GLT8D2	1e-07	Tier 4: intronic/intergenic
rs145242146	8	141369396	G>A	0.022	intron_variant	GPR20 - ASTILCS	1e-07	Tier 4: intronic/intergenic
rs34437832	10	119077771	T>C	0.04	intron_variant	EIF3A	1e-07	Tier 4: intronic/intergenic
rs1754257	10	25385685	G>A	0.24	intron_variant	GPR158	2e-07	Tier 4: intronic/intergenic
rs76398191	10	18819130	T>C,G	0.31	intron_variant	AIFM1P1 - MALRD1	2e-07	Tier 4: intronic/intergenic
rs10456404	6	32245080	T>A,C	0.13	regulatory_region_variant	NOTCH4 - TSBP1-AS1	2e-07	Tier 3: regulatory
rs62577031	9	135451532	A>C,G,T	0.023	intron_variant	PPP1R26-AS1	2e-07	Tier 4: intronic/intergenic
rs9380516	6	35534425	T>C,G	0.17	regulatory_region_variant	LINC03135	5e-07	Tier 3: regulatory
rs28368843	6	32484810	C>T	0.07	intron_variant	HLA-DRB9 - HLA-DRB5	5e-07	Tier 4: intronic/intergenic
rs6087561	20	34196021	T>A,C	0.12	intron_variant	ASIP	6e-07	Tier 4: intronic/intergenic
rs1346763	2	114515136	C>A,G,T	0.32	intron_variant	DPP10	9e-07	Tier 4: intronic/intergenic
rs1649709	7	52712519	A>C,G	0.41	intergenic_variant	RN7SL292P - SGO1P2	9e-07	Tier 4: intronic/intergenic
rs7262634	20	47205635	T>C	0.05	intron_variant	EYA2 - ZMYND8	1e-06	Tier 4: intronic/intergenic
rs2978048	8	133603893	T>C,G	0.05	intergenic_variant	ST3GAL1-DT - LINC03024	1e-06	Tier 4: intronic/intergenic
kgp3085785							1e-06	Tier 4: intronic/intergenic
rs883924	9	90419249	G>A	0.26	intron_variant	LINC01508	2e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TULP1	Orphanet:65	Leber congenital amaurosis
TULP1	Orphanet:791	Retinitis pigmentosa
PKD1L1	Orphanet:101063	Situs inversus totalis
PKD1L1	Orphanet:157769	Situs ambiguus
FGF14	Orphanet:675216	Spinocerebellar ataxia type 27B
FGF14	Orphanet:98764	Spinocerebellar ataxia type 27A
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid
HLA-DQB1	Orphanet:83465	Narcolepsy type 2
HLA-DQB1	Orphanet:930	Idiopathic achalasia
KCNH5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
MERTK	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

20 cohort genes, 20 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	20

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF7	HGNC:10070	ENSG00000114125	Q9UBF6	RING-box protein 2	gwas
RPL39	HGNC:10350	ENSG00000198918	P62891	Large ribosomal subunit protein eL39	gwas
RUNX3	HGNC:10473	ENSG00000020633	Q13761	Runt-related transcription factor 3	gwas
ST3GAL1	HGNC:10862	ENSG00000008513	Q11201	CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 1	gwas
TULP1	HGNC:12423	ENSG00000112041	O00294	Tubby-related protein 1	gwas
SEPTIN6	HGNC:15848	ENSG00000125354	Q14141	Septin-6	gwas
PKD1L1	HGNC:18053	ENSG00000158683	Q8TDX9	Polycystin-1-like protein 1	gwas
IFNL3	HGNC:18365	ENSG00000197110	Q8IZI9	Interferon lambda-3	gwas
PITPNC1	HGNC:21045	ENSG00000154217	Q9UKF7	Cytoplasmic phosphatidylinositol transfer protein 1	gwas
ARL5B	HGNC:23052	ENSG00000165997	Q96KC2	ADP-ribosylation factor-like protein 5B	gwas
GPR158	HGNC:23689	ENSG00000151025	Q5T848	Metabotropic glycine receptor	gwas
GLT8D2	HGNC:24890	ENSG00000120820	Q9H1C3	Glycosyltransferase 8 domain-containing protein 2	gwas
TMEM18	HGNC:25257	ENSG00000151353	Q96B42	Transmembrane protein 18	gwas
FGF14	HGNC:3671	ENSG00000102466	Q92915	Fibroblast growth factor 14	gwas
IFNL4	HGNC:44480	ENSG00000272395	K9M1U5	Interferon lambda-4	gwas
HLA-DQA2	HGNC:4943	ENSG00000237541	P01906	HLA class II histocompatibility antigen, DQ alpha 2 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
KCNH5	HGNC:6254	ENSG00000140015	Q8NCM2	Voltage-gated delayed rectifier potassium channel KCNH5	gwas
MERTK	HGNC:7027	ENSG00000153208	Q12866	Tyrosine-protein kinase Mer	gwas
ZMYND8	HGNC:9397	ENSG00000101040	Q9ULU4	MYND-type zinc finger-containing chromatin reader ZMYND8	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF7	RING-box protein 2	Catalytic component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.
RPL39	Large ribosomal subunit protein eL39	RNA-binding component of the large ribosomal subunit.
RUNX3	Runt-related transcription factor 3	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
ST3GAL1	CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 1	A beta-galactoside alpha2->3 sialyltransferase involved in terminal sialylation of glycoproteins and glycolipids.
TULP1	Tubby-related protein 1	Required for normal development of photoreceptor synapses.
SEPTIN6	Septin-6	Filament-forming cytoskeletal GTPase.
PKD1L1	Polycystin-1-like protein 1	Component of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, without affecting cytoplasmic calcium concentration, and regulates sonic hedgehog/SHH signaling and G…
IFNL3	Interferon lambda-3	Cytokine with antiviral, antitumour and immunomodulatory activities.
PITPNC1	Cytoplasmic phosphatidylinositol transfer protein 1	Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidic acid (PA) between membranes.
ARL5B	ADP-ribosylation factor-like protein 5B	Binds and exchanges GTP and GDP.
GPR158	Metabotropic glycine receptor	Metabotropic receptor for glycine that controls synapse formation and function in the brain.
TMEM18	Transmembrane protein 18	Transcription repressor.
FGF14	Fibroblast growth factor 14	Probably involved in nervous system development and function.
IFNL4	Interferon lambda-4	Cytokine that may trigger an antiviral response activating the JAK-STAT pathway and up-regulating specifically some interferon-stimulated genes.
HLA-DQA2	HLA class II histocompatibility antigen, DQ alpha 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
KCNH5	Voltage-gated delayed rectifier potassium channel KCNH5	Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate.
MERTK	Tyrosine-protein kinase Mer	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6.
ZMYND8	MYND-type zinc finger-containing chromatin reader ZMYND8	Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at ‘Lys-36’ and histone H4 acetylated at ‘Lys-16’ (H3.1K36me2-H4K16ac) and histone H3 methylated at ‘Lys-4’ and histone H4 acetylated at ‘Lys-14’…

Protein-family classification

Druggable: 7 · Difficult: 3 · Unknown: 10 · Druggable fraction: 0.35

Family distribution

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

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	3	4.4×	0.207
Ion channel	1	5.6×	0.577
Kinase	1	1.4×	0.804
Transcription factor	3	1.2×	0.804
GPCR	1	1.2×	0.804
Other/Unknown	10	0.9×	0.825
Enzyme (other)	1	0.6×	0.825

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF7	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_H2
RPL39	Other/Unknown	no		Ribosomal_eL39, Ribosomal_eL39_CS, Ribosomal_eL39_dom_sf
RUNX3	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
ST3GAL1	Enzyme (other)	yes	2.4.99.2	Glyco_trans_29, Sialyl_trans, GT29-like_sf
TULP1	Other/Unknown	no		Tubby_C, Tubby_C_CS, Tubby-like_C
SEPTIN6	Other/Unknown	no		Septin, P-loop_NTPase, G_SEPTIN_dom
PKD1L1	Antibody/Immunoglobulin	yes		PKD_dom, PLAT/LH2_dom, PKD/REJ-like
IFNL3	Other/Unknown	no		INF_lambda, IFN-lambda_sf
PITPNC1	Other/Unknown	no		PI_transfer, START-like_dom_sf, PI_transfer_N
ARL5B	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF
GPR158	GPCR	yes		GPCR_3_C, GPR158/179, GPR158_179_extracellular
GLT8D2	Other/Unknown	no		Glyco_trans_8, Nucleotide-diphossugar_trans, Glycosyltrans_8_dom-fam
TMEM18	Other/Unknown	no		TMEM18
FGF14	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
IFNL4	Other/Unknown	no		INF_lambda, IFN-lambda_sf
HLA-DQA2	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
KCNH5	Ion channel	yes		PAS, cNMP-bd_dom, PAS-assoc_C
MERTK	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub
ZMYND8	Transcription factor	no		PWWP_dom, Bromodomain, Znf_PHD

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	2
broad (>20)	18
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	5
granulocyte	4
primordial germ cell in gonad	4
right adrenal gland	2
buccal mucosa cell	2
lymph node	2
cartilage tissue	2
endothelial cell	2
middle temporal gyrus	2
secondary oocyte	2
left adrenal gland	1
left adrenal gland cortex	1
endometrium	1
ganglionic eminence	1
ventricular zone	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1
retina	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF7	292	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, right adrenal gland
RPL39	134	ubiquitous	marker	ganglionic eminence, endometrium, ventricular zone
RUNX3	220	broad	marker	granulocyte, buccal mucosa cell, lymph node
ST3GAL1	253	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TULP1	134	tissue_specific	marker	primordial germ cell in gonad, tendon of biceps brachii, retina
SEPTIN6	278	ubiquitous	marker	thymus, lymph node, granulocyte
PKD1L1	150	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, apex of heart, primordial germ cell in gonad
IFNL3	15		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, granulocyte
PITPNC1	275	ubiquitous	marker	endothelial cell, cortical plate, cartilage tissue
ARL5B	254	ubiquitous	marker	vena cava, epithelial cell of pancreas, cartilage tissue
GPR158	127	broad	marker	endothelial cell, middle temporal gyrus, cerebellar vermis
GLT8D2	247	ubiquitous	marker	tibia, parietal pleura, descending thoracic aorta
TMEM18	259	ubiquitous	marker	calcaneal tendon, kidney epithelium, sural nerve
FGF14	200	broad	marker	secondary oocyte, middle temporal gyrus, bronchial epithelial cell
IFNL4	18		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, prefrontal cortex
HLA-DQA2	127	broad	marker	granulocyte, vermiform appendix, male germ line stem cell (sensu Vertebrata) in testis
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
KCNH5	83	tissue_specific	marker	buccal mucosa cell, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
MERTK	246	ubiquitous	marker	right adrenal gland cortex, mucosa of stomach, right adrenal gland
ZMYND8	300	ubiquitous	marker	corpus epididymis, oocyte, caput epididymis

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RUNX3	3,293
MERTK	2,735
ARL5B	2,585
RNF7	2,453
FGF14	1,675
HLA-DQA2	1,611
ZMYND8	1,466
GPR158	1,437
SEPTIN6	1,336
ST3GAL1	967

Intra-cohort edges

A	B	Sources
MERTK	PITPNC1	string_interaction
MERTK	TULP1	string_interaction

Structural data

PDB: 13 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL39	P62891	181
MERTK	Q12866	42
HLA-DQB1	P01920	10
ZMYND8	Q9ULU4	8
RNF7	Q9UBF6	7
GPR158	Q5T848	6
KCNH5	Q8NCM2	6
SEPTIN6	Q14141	4
IFNL3	Q8IZI9	3
TULP1	O00294	2
RUNX3	Q13761	1
ARL5B	Q96KC2	1
IFNL4	K9M1U5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ST3GAL1	Q11201	89.97
TMEM18	Q96B42	89.83
HLA-DQA2	P01906	89.29
GLT8D2	Q9H1C3	88.41
PITPNC1	Q9UKF7	83.27
FGF14	Q92915	79.77
PKD1L1	Q8TDX9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 80. Enrichment computed across 20 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates RUNX1-mediated transcription	1	346.1×	0.070	RUNX3
RUNX3 regulates BCL2L11 (BIM) transcription	1	207.6×	0.070	RUNX3
RUNX3 Regulates Immune Response and Cell Migration	1	173.0×	0.070	RUNX3
RUNX3 regulates CDKN1A transcription	1	148.3×	0.070	RUNX3
RUNX3 regulates YAP1-mediated transcription	1	129.8×	0.070	RUNX3
Maturation of protein 3a	1	115.3×	0.070	ST3GAL1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	103.8×	0.070	RUNX3
RUNX3 regulates WNT signaling	1	103.8×	0.070	RUNX3
RUNX3 regulates p14-ARF	1	103.8×	0.070	RUNX3
Interferon gamma signaling	2	22.8×	0.070	HLA-DQA2, HLA-DQB1
Translation of Structural Proteins	1	79.9×	0.077	ST3GAL1
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	79.9×	0.077	RUNX3
RUNX3 regulates NOTCH signaling	1	74.2×	0.077	RUNX3
Translocation of ZAP-70 to Immunological synapse	1	57.7×	0.092	HLA-DQA2
Phosphorylation of CD3 and TCR zeta chains	1	49.4×	0.092	HLA-DQA2
Co-inhibition by PD-1	1	47.2×	0.092	HLA-DQA2
Keratan sulfate/keratin metabolism	1	45.1×	0.092	ST3GAL1
Termination of O-glycan biosynthesis	1	45.1×	0.092	ST3GAL1
Inactivation of CSF3 (G-CSF) signaling	1	39.9×	0.097	RNF7
Interleukin-20 family signaling	1	38.5×	0.097	IFNL3
Translation of Structural Proteins	1	37.1×	0.097	ST3GAL1
Keratan sulfate biosynthesis	1	34.6×	0.099	ST3GAL1
Generation of second messenger molecules	1	31.5×	0.100	HLA-DQA2
Phase 0 - rapid depolarisation	1	31.5×	0.100	FGF14
Sialic acid metabolism	1	29.7×	0.102	ST3GAL1
Synthesis of substrates in N-glycan biosythesis	1	26.6×	0.106	ST3GAL1
Late SARS-CoV-2 Infection Events	1	26.6×	0.106	ST3GAL1
Transcriptional regulation by RUNX3	1	24.7×	0.107	RUNX3
Maturation of spike protein	1	24.1×	0.107	ST3GAL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 19 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 immune response	4	101.4×	8e-06	IFNL3, IFNL4, HLA-DQA2, HLA-DQB1
type III interferon-mediated signaling pathway	2	161.3×	0.004	IFNL3, IFNL4
peptide antigen assembly with MHC class II protein complex	2	110.9×	0.006	HLA-DQA2, HLA-DQB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	2	57.2×	0.017	HLA-DQA2, HLA-DQB1
positive regulation of T cell activation	2	46.7×	0.021	HLA-DQA2, HLA-DQB1
memory B cell differentiation	1	887.0×	0.024	ST3GAL1
negative regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1	443.5×	0.029	ST3GAL1
protein sialylation	1	443.5×	0.029	ST3GAL1
negative regulation of leukocyte apoptotic process	1	443.5×	0.029	MERTK
positive regulation of phagocytosis	2	33.5×	0.029	TULP1, MERTK
retina development in camera-type eye	2	26.9×	0.029	TULP1, MERTK
detection of nodal flow	1	295.6×	0.033	PKD1L1
negative regulation of lymphocyte activation	1	295.6×	0.033	MERTK
negative regulation of CD4-positive, alpha-beta T cell differentiation	1	221.7×	0.034	RUNX3
negative regulation of focal adhesion disassembly	1	221.7×	0.034	RNF7
regulation of postsynaptic density protein 95 clustering	1	221.7×	0.034	ZMYND8
cellular response to virus	2	21.1×	0.034	IFNL3, IFNL4
N-acetylneuraminate metabolic process	1	177.4×	0.036	ST3GAL1
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	177.4×	0.036	RUNX3
positive regulation of dendritic spine maintenance	1	177.4×	0.036	ZMYND8
tyrosine phosphorylation of STAT protein	1	147.8×	0.039	IFNL4
neutrophil clearance	1	147.8×	0.039	MERTK
protein localization to photoreceptor outer segment	1	126.7×	0.042	TULP1
nervous system development	3	7.2×	0.042	FGF14, MERTK, ZMYND8
phagocytosis, recognition	1	110.9×	0.042	TULP1
modulation of excitatory postsynaptic potential	1	110.9×	0.042	ZMYND8
protein localization to Golgi membrane	1	110.9×	0.042	ARL5B
positive regulation of neurotransmitter secretion	1	98.5×	0.043	GPR158
response to transforming growth factor beta	1	98.5×	0.043	RUNX3
sialylation	1	98.5×	0.043	ST3GAL1

Therapeutics

Drugs indicated for this disease

5 approved, 33 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ledipasvir	Approved (phase 4)
Ombitasvir	Approved (phase 4)
Paritaprevir	Approved (phase 4)
Ritonavir	Approved (phase 4)
Sofosbuvir	Approved (phase 4)
Alisporivir	Phase 3 (in late-stage trials)
Asunaprevir	Phase 3 (in late-stage trials)
Beclabuvir	Phase 3 (in late-stage trials)
Boceprevir	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Daclatasvir	Phase 3 (in late-stage trials)
Dasabuvir	Phase 3 (in late-stage trials)
Elbasvir	Phase 3 (in late-stage trials)
Eltrombopag	Phase 3 (in late-stage trials)
Epoetin Alfa	Phase 3 (in late-stage trials)
Faldaprevir	Phase 3 (in late-stage trials)
Furaprevir	Phase 3 (in late-stage trials)
Glecaprevir	Phase 3 (in late-stage trials)
Grazoprevir Anhydrous	Phase 3 (in late-stage trials)
INTERFERON ALFA-2A	Phase 3 (in late-stage trials)
INTERFERON ALFA-2B	Phase 3 (in late-stage trials)
INTERFERON ALFACON-1	Phase 3 (in late-stage trials)
INTERFERON BETA-1A	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Narlaprevir	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2A	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2B	Phase 3 (in late-stage trials)
PEGINTERFERON LAMBDA-1A	Phase 3 (in late-stage trials)
POLYETHYLENE GLYCOL 3350	Phase 3 (in late-stage trials)
Pibrentasvir	Phase 3 (in late-stage trials)
Ribavirin	Phase 3 (in late-stage trials)
Silybin A	Phase 3 (in late-stage trials)
Simeprevir	Phase 3 (in late-stage trials)
Telaprevir	Phase 3 (in late-stage trials)
Thymalfasin	Phase 3 (in late-stage trials)
Yimitasvir	Phase 3 (in late-stage trials)
Zinc Ion	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ALBINTERFERON ALFA-2B, Ademetionine, Amantadine, Atorvastatin, Betaine, Candesartan, Cannabinol, Cyclosporine, Danoprevir, Ergocalciferol, Everolimus, Filibuvir, Fluvastatin, Infliximab, Mifepristone, Nitazoxanide, Pioglitazone, Pradigastat, Prednisone, Protease (Pancrelipase), Rifaximin, Rosuvastatin, Silibinin, Sodium Chloride, Tacrolimus Anhydrous, Thalidomide, Vaniprevir, Velpatasvir.

Drug target analysis

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

Druggability breadth: 8 of 20 evidence-associated genes (40%) 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
RPL39	GENTAMICIN SULFATE
MERTK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MERTK	48	4
RPL39	1	4
ZMYND8	1	2
RNF7	0	0
RUNX3	0	0
ST3GAL1	0	0
TULP1	0	0
SEPTIN6	0	0
PKD1L1	0	0
IFNL3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL39
FEDRATINIB	4	MERTK
AXITINIB	4	MERTK
SORAFENIB	4	MERTK
NERATINIB	4	MERTK
CABOZANTINIB	4	MERTK
VANDETANIB	4	MERTK
BOSUTINIB	4	MERTK
FILGOTINIB	4	MERTK
PACLITAXEL	4	MERTK
PAZOPANIB	4	MERTK
NINTEDANIB	4	MERTK
SUNITINIB	4	MERTK
ERLOTINIB	4	MERTK
QUIZARTINIB	4	MERTK
CRIZOTINIB	4	MERTK
MIDOSTAURIN	4	MERTK
LINIFANIB	3	MERTK
ITACITINIB	3	MERTK
ALVOCIDIB	3	MERTK
SURUFATINIB	3	MERTK
CEDIRANIB	3	MERTK
POVORCITINIB	3	MERTK
DOVITINIB	3	MERTK
LESTAURTINIB	3	MERTK
DORAMAPIMOD	2	MERTK
FORETINIB	2	MERTK
TANDUTINIB	2	MERTK
SU-014813	2	MERTK
REBASTINIB	2	MERTK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
MERTK	443	Binding:442, Functional:1
RPL39	89	Binding:89
KCNH5	21	Binding:20, Toxicity:1
FGF14	16	Binding:16
ZMYND8	12	Binding:12
ST3GAL1	4	Binding:4
GPR158	2	Binding:2
SEPTIN6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ST3GAL1	2.4.99.2, 2.4.99.4	beta-D-galactosyl-(1->3)-N-acetyl-beta-D-galactosaminide alpha-2,3-sialyltransferase, beta-galactoside alpha-2,3-sialyltransferase
MERTK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MERTK	443

Pharmacogenomics

Cohort genes with a PharmGKB record: 20; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
IFNL3	1

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
GENTAMICIN SULFATE	4	RPL39
FEDRATINIB	4	MERTK
AXITINIB	4	MERTK
SORAFENIB	4	MERTK
NERATINIB	4	MERTK
CABOZANTINIB	4	MERTK
VANDETANIB	4	MERTK
BOSUTINIB	4	MERTK
FILGOTINIB	4	MERTK
PACLITAXEL	4	MERTK
PAZOPANIB	4	MERTK
NINTEDANIB	4	MERTK
SUNITINIB	4	MERTK
ERLOTINIB	4	MERTK
QUIZARTINIB	4	MERTK
CRIZOTINIB	4	MERTK
MIDOSTAURIN	4	MERTK
LINIFANIB	3	MERTK
ITACITINIB	3	MERTK
ALVOCIDIB	3	MERTK
SURUFATINIB	3	MERTK
CEDIRANIB	3	MERTK
POVORCITINIB	3	MERTK
DOVITINIB	3	MERTK
LESTAURTINIB	3	MERTK
DORAMAPIMOD	2	MERTK
FORETINIB	2	MERTK
TANDUTINIB	2	MERTK
SU-014813	2	MERTK
REBASTINIB	2	MERTK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RPL39, MERTK
B	Phased (≥1) drug, not yet approved	1	ZMYND8
C	Druggable family + PDB, no drug	3	GPR158, HLA-DQB1, KCNH5
D	Druggable family + AlphaFold only, no drug	3	ST3GAL1, PKD1L1, HLA-DQA2
E	Difficult family or no structure, no drug	11	RNF7, RUNX3, TULP1, SEPTIN6, IFNL3, PITPNC1, ARL5B, GLT8D2, TMEM18, FGF14 (+1 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)
TULP1	0	MERTK
PITPNC1	0	MERTK
RNF7	0	—
RUNX3	0	—
ST3GAL1	4	—
SEPTIN6	1	—
PKD1L1	0	—
IFNL3	0	—
ARL5B	0	—
GPR158	2	—
GLT8D2	0	—
TMEM18	0	—
FGF14	16	—
IFNL4	0	—
HLA-DQA2	0	—
HLA-DQB1	0	—
KCNH5	21	—

Clinical trials & evidence

Clinical trials

Clinical trials: 590.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	162
PHASE2	137
PHASE3	118
PHASE4	68
PHASE1	67
PHASE1/PHASE2	22
PHASE2/PHASE3	14
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07098481	PHASE4	NOT_YET_RECRUITING	Access to Hepatitis C Treatment in Cameroon: Comparison of a Simplified Test and Treat Strategy to a Standard Strategy
NCT00001854	PHASE4	COMPLETED	Long-Term Therapy With Ribavirin for Chronic Hepatitis C
NCT00028093	PHASE4	COMPLETED	Pegylated Interferon and Ribavirin to Treat Chronic Hepatitis C With and Without Kidney Disease
NCT00172809	PHASE4	COMPLETED	Interferon Treatment for Patients With Chronic Hepatitis C and End Stage Renal Disease
NCT00189163	PHASE4	COMPLETED	Pioglitazone in Hepatitis C
NCT00209898	PHASE4	TERMINATED	Hepatitis C Treatment of Inmates
NCT00245414	PHASE4	COMPLETED	Trial of Pegasys® in Patients With Chronic Hepatitis C
NCT00274495	PHASE4	TERMINATED	Assessing the Efficacy and Safety of Rosiglitazone Added to Standard Therapy for Hepatitis C Genotype 1 With Fatty Liver
NCT00298714	PHASE4	COMPLETED	Effects of Losartan on Hepatic Fibrogenesis in Chronic Hepatitis C
NCT00351871	PHASE4	COMPLETED	Influence of Marker of Insulin Resistance Upon Hepatitis C Virus (HCV) Treatment Responses to PEG Intron and Rebetol Therapy
NCT00370617	PHASE4	UNKNOWN	Pegylated-Interferon and Ribavirin Plus Metformin in the Treatment of Chronic HCV Infection and Insulin Resistance
NCT00491179	PHASE4	COMPLETED	Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin
NCT00491244	PHASE4	COMPLETED	Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin for Treatment-Naïve Hemodialysis Patients With Chronic Hepatitis C
NCT00526448	PHASE4	UNKNOWN	Phase IV Study to Evaluate the Efficacy/Safety to Extend Treatment and High Dose of Ribavirin in co-Infected Patients
NCT00530972	PHASE4	COMPLETED	Pilot Study of Patients Chronic Hepatitis C in Co-infected HIV Patients Relapsers After Previous Therapies
NCT00532701	PHASE4	COMPLETED	Peginterferon Alfa-2a and Ribavirin for Genotype 2 Chronic Hepatitis C: Duration and Ribavirin Dose Stratified by RVR
NCT00540345	PHASE4	COMPLETED	Four Arms, Multicenter Study of Tailored Regimens With Peginterferon Plus Ribavirin for Genotype 2 Chronic Hepatitis C
NCT00546442	PHASE4	COMPLETED	Treatment Insulin Resistence in HCV G-1 Patient
NCT00575224	PHASE4	COMPLETED	Pegasys and Copegus for Asian Patients With Treatment-naive Hepatitis C Genotypes 6, 7, 8, 9
NCT00575627	PHASE4	UNKNOWN	Pegylated-Interferon and Ribavirin in Hepatitis C Patients With Persistently Normal Alanine Aminotransferase Levels
NCT00611819	PHASE4	UNKNOWN	Two Different Treatments 24 vs 48 Weeks Chronic Hepatitis C Genotypes 2 and/or 3 in co-Infected HIV-HCV
NCT00629824	PHASE4	COMPLETED	Pegylated Interferon Plus Ribavirin in Treating Older Patients With Chronic Hepatitis C
NCT00629967	PHASE4	COMPLETED	A Randomized Trial of 24-Week Versus 48-Week Courses of Peginterferon Plus Ribavirin for HCV Genotype-1 Patients
NCT00630084	PHASE4	COMPLETED	Peginterferon Plus Ribavirin for Hepatitis C Patients Concomitant With Malignancy Other Than Hepatocellular Carcinoma
NCT00641654	PHASE4	TERMINATED	Combination Therapy With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After Therapy With Pegylated Interferon and Ribavirin
NCT00680173	PHASE4	COMPLETED	Peripheral Blood Mononuclear Cell (PBMC) Gene Expression in HCV Genotype 1 Patients
NCT00830609	PHASE4	COMPLETED	High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3
NCT00834860	PHASE4	UNKNOWN	Peginterferon Plus Ribavirin for Hepatitis C Patients Concomitant With Hepatocellular Carcinoma
NCT00844272	PHASE4	COMPLETED	Psychoeducation Reaches HCV-infected Methadone/Buprenorphine Substituted Patients in Standard Antiviral Treatment
NCT00881582	PHASE4	COMPLETED	Peginterferon Alfa-2a Plus Ribavirin Combination Treatment in Chronic Hepatitis C Post-Renal Transplant Patients
NCT00957866	PHASE4	COMPLETED	Prospective Anti-Hepatitis C Virus (Anti-HCV) Trial of Peg-Interferon and Ribavirin in Subjects of First Nations, Metis and Caucasian Ethnicity
NCT01025765	PHASE4	UNKNOWN	The Effects of Oral Hypoglycemic Agents on Chronic Hepatitis C Patients Receiving Peg-Intron Plus Ribavirin
NCT01056172	PHASE4	UNKNOWN	PegIFN Alfa-2a and RBV for 16 or 24 Weeks in Patients With Chronic Hepatitis C(CHC) 2 With Rapid Virologic Response(RVR)
NCT01120795	PHASE4	COMPLETED	Pegylated Interferon and Ribavirin in Hepatitis C Patients on Opioid Pharmacotherapy
NCT01405027	PHASE4	COMPLETED	Impact of Physician Directed Education on Patient Compliance With Hepatitis C Therapy
NCT01413360	PHASE4	COMPLETED	The Effect of High Dose Vitamin C on the Liver Function in Chronic Hepatitis Patients
NCT01439776	PHASE4	COMPLETED	Add Vitamin D With Standard of Care for Chronic Hepatitis C Patients
NCT01596517	PHASE4	COMPLETED	Efficacy and Effectiveness of PegInterferon and Ribavirin in Korean Patients With Chronic Hepatitis C
NCT01649245	PHASE4	UNKNOWN	Hansenula-derived Pegylated Interferon in Treatment of Patients With Chronic Hepatitis C
NCT01683786	PHASE4	UNKNOWN	36 vs 48 Wks Peg-Intron Plus Ribavirin for HCV Patients Without Rapid Virologic Response But Without HCV RNA at wk 8

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RIBAVIRIN	4	166
PARITAPREVIR	4	40
OMBITASVIR	4	29
DACLATASVIR	4	28
PEGINTERFERON ALFA-2A	4	22
DASABUVIR	4	20
GRAZOPREVIR ANHYDROUS	4	20
SOFOSBUVIR	4	19
TELAPREVIR	4	17
GLECAPREVIR	4	13
PIBRENTASVIR	4	12
PEGINTERFERON ALFA-2B	4	11
SIMEPREVIR	4	11
ASUNAPREVIR	4	10
BOCEPREVIR	4	10
VELPATASVIR	4	10
ELBASVIR	4	7
LEDIPASVIR	4	7
NITAZOXANIDE	4	7
PAROXETINE	4	4
METFORMIN	4	3
VALACYCLOVIR	4	3
BETAINE	4	2
INTERFERON ALFA-2A	4	2
PIOGLITAZONE	4	2
VOXILAPREVIR	4	2
ACARBOSE	4	1
AMANTADINE	4	1
CYANOCOBALAMIN	4	1
ENTECAVIR	4	1