chronic hepatitis C virus infection

Summary

chronic hepatitis C virus infection (MONDO:0005354) is a disease with 17 cohort genes (36 GWAS associations across 17 studies) and 811 clinical trials. The dominant Reactome pathway is Interleukin-20 family signaling (3 cohort genes). Top therapeutic interventions include ribavirin, peginterferon alfa-2a, and simeprevir.

At a glance

• Cohort genes: 17
• GWAS associations: 36
• Clinical trials: 811

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic hepatitis C virus infection
Mondo ID	MONDO:0005354
EFO	EFO:0004220
MeSH	D019698
ICD-11	1615937473
Is cancer (heuristic)	no

Also known as: chronic Hepatitis C · hepatitis C infection, chronic · hepatitis C, chronic

Data availability: 36 GWAS associations (17 studies).

Disease family

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 › chronic hepatitis C virus infection

Related subtypes (1): acute hepatitis C virus infection

Genetics & variants

GWAS landscape

36 GWAS associations across 17 studies. Top hits map to 13 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs7270101	9e-76	ITPA	C
rs1127354	2e-58	ITPA	A
rs8099917	3e-32	IFNL4 - MSRB1P1	G	27.1
rs12979860	2e-30	IFNL4	?	2.2
rs8113007	7e-28	IFNL4 - MSRB1P1	T	1.43
rs6139030	2e-25	DDRGK1 - ITPA	T	25
rs11697186	9e-25	DDRGK1	A	33.33
rs4803217	1e-22	IFNL3	A	0.29
rs4273729	5e-17	MTCO3P1 - HLA-DQB3	?	1.59
rs9275572	4e-16	MTCO3P1 - HLA-DQB3	T	1.27
rs1012068	1e-13	DEPDC5	G	1.75
rs9275263	2e-12	HLA-DQB1 - MTCO3P1	G	0.12
rs9275267	3e-12	HLA-DQB1 - MTCO3P1	G	0.12
rs2853968	2e-10	MICA	G	0.11
rs965469	1e-09	DNAAF9	?
rs709053	2e-09	HLA-B	G	0.11
chr1:225536401	5e-08		C	1.96
rs10776934	1e-06	OLFM1 - LINC02907	T	0.28
rs10789491	1e-06	EFCAB14	G	0.31
rs2504916	2e-06	SLC22A3	T	0.31
rs16864968	3e-06	HIGD1AP4 - SCG2	G	0.83
rs2254135	3e-06	RCC2 - ARHGEF10L	T	0.27
rs11242704	5e-06	ELF2P2 - FOXCUT	G	0.26
rs9400317	7e-06	AK9	?
rs12527818	7e-06	COPS5P1 - EPHA7	T	0.27
rs12144715	7e-06	DNASE2B	T	0.64
rs17067123	8e-06	RNA5SP173 - NDUFB5P1	?
rs11725957	8e-06	CWH43	G	0.73

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90018585	Sakaue S	2021	7,110	169,588	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90013691	Ishigaki K	2020	5,794	206,659	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST90013733	Ishigaki K	2020	3,159	106,188	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST90013768	Ishigaki K	2020	2,635	100,471	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST000944	Ochi H	2011	2,101	0	IL-28B predicts response to chronic hepatitis C therapy–fine-mapping and replication study in Asian populations.
GCST001867	Duggal P	2013	1,482	0	Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.
GCST000604	Fellay J	2010	988	0	ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C.
GCST001076	Thompson AJ	2011	984	0	Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients.
GCST000465	Ge D	2009	871	0	Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.
GCST001325	Lange CM	2011	707	0	Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy.

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	25

MAF distribution

Bucket	Variants
common (>=0.05)	27
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	13
intergenic_variant	10
missense_variant	1
3_prime_UTR_variant	1
synonymous_variant	1
unknown	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs7270101	20	3213247	A>C,T	0.11	intron_variant	ITPA	9e-76	Tier 4: intronic/intergenic
rs1127354	20	3213196	C>A,G,T	0.069	missense_variant	ITPA	2e-58	Tier 1: coding
rs8099917	19	39252525	T>G	0.12	intergenic_variant	IFNL4 - MSRB1P1	3e-32	Tier 4: intronic/intergenic
rs12979860	19	39248147	C>G,T	0.05	intron_variant	IFNL4	2e-30	Tier 4: intronic/intergenic
rs8113007	19	39252463	A>T	0.104	intergenic_variant	IFNL4 - MSRB1P1	7e-28	Tier 4: intronic/intergenic
rs6139030	20	3207087	T>C	0.17	intron_variant	DDRGK1 - ITPA	2e-25	Tier 4: intronic/intergenic
rs11697186	20	3204477	A>C,G,T	0.15	intron_variant	DDRGK1	9e-25	Tier 4: intronic/intergenic
rs4803217	19	39243580	C>A,G,T	0.106	3_prime_UTR_variant	IFNL3	1e-22	Tier 2: splice/UTR
rs4273729	6	32710820	C>A,G,T	0.05	intergenic_variant	MTCO3P1 - HLA-DQB3	5e-17	Tier 4: intronic/intergenic
rs9275572	6	32711222	A>G,T	0.359	intergenic_variant	MTCO3P1 - HLA-DQB3	4e-16	Tier 4: intronic/intergenic
rs1012068	22	31869917	T>A,C,G	0.12	intron_variant	DEPDC5	1e-13	Tier 4: intronic/intergenic
rs9275263	6	32694567	A>C,G	0.05	intergenic_variant	HLA-DQB1 - MTCO3P1	2e-12	Tier 4: intronic/intergenic
rs9275267	6	32694648	A>G,T	0.376	intergenic_variant	HLA-DQB1 - MTCO3P1	3e-12	Tier 4: intronic/intergenic
rs2853968	6	31413574	A>G,T	0.05	intron_variant	MICA	2e-10	Tier 4: intronic/intergenic
rs965469	20	3400902	T>C	0.05	intron_variant	DNAAF9	1e-09	Tier 4: intronic/intergenic
rs709053	6	31356300	C>A,G,T	0.468	synonymous_variant	HLA-B	2e-09	Tier 4: intronic/intergenic
chr1:225536401							5e-08	Tier 4: intronic/intergenic
rs10776934	9	135137855	T>A,G	0.05	regulatory_region_variant	OLFM1 - LINC02907	1e-06	Tier 3: regulatory
rs10789491	1	46713638	A>C,G,T	0.05	intron_variant	EFCAB14	1e-06	Tier 4: intronic/intergenic
rs2504916	6	160402996	T>A,C,G	0.05	intron_variant	SLC22A3	2e-06	Tier 4: intronic/intergenic
rs16864968	2	223594965	A>G	0.05	intergenic_variant	HIGD1AP4 - SCG2	3e-06	Tier 4: intronic/intergenic
rs2254135	1	17508246	C>A,G,T	0.05	intergenic_variant	RCC2 - ARHGEF10L	3e-06	Tier 4: intronic/intergenic
rs11242704	6	1535763	A>G,T	0.05	intron_variant	ELF2P2 - FOXCUT	5e-06	Tier 4: intronic/intergenic
rs9400317	6	109686444	A>G,T	0.05	intron_variant	AK9	7e-06	Tier 4: intronic/intergenic
rs12527818	6	93201401	T>A,C,G	0.05	intergenic_variant	COPS5P1 - EPHA7	7e-06	Tier 4: intronic/intergenic
rs12144715	1	84399547	A>T	0.05	intron_variant	DNASE2B	7e-06	Tier 4: intronic/intergenic
rs17067123	4	179127208	C>T	0.05	intergenic_variant	RNA5SP173 - NDUFB5P1	8e-06	Tier 4: intronic/intergenic
rs11725957	4	49060875	G>A,C	0.05	intron_variant	CWH43	8e-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
DDRGK1	Orphanet:93352	Spondyloepimetaphyseal dysplasia, Shohat type
DEPDC5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
DEPDC5	Orphanet:98784	Sleep-related hypermotor epilepsy
DEPDC5	Orphanet:98820	Familial focal epilepsy with variable foci
AK9	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
HLA-DQA1	Orphanet:391490	Adult-onset myasthenia gravis
HLA-DQA1	Orphanet:930	Idiopathic achalasia
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
ITPA	Orphanet:457375	ITPA-related lethal infantile neurological disorder with cataract and cardiac involvement

Cohort genes → proteins

17 cohort genes, 17 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	17

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCG2	HGNC:10575	ENSG00000171951	P13521	Secretogranin-2	gwas
SLC22A3	HGNC:10967	ENSG00000146477	O75751	Solute carrier family 22 member 3	gwas
DDRGK1	HGNC:16110	ENSG00000198171	Q96HY6	DDRGK domain-containing protein 1	gwas
OLFM1	HGNC:17187	ENSG00000130558	Q99784	Noelin	gwas
IFNL1	HGNC:18363	ENSG00000182393	Q8IU54	Interferon lambda-1	gwas
IFNL2	HGNC:18364	ENSG00000183709	Q8IZJ0	Interferon lambda-2	gwas
IFNL3	HGNC:18365	ENSG00000197110	Q8IZI9	Interferon lambda-3	gwas
DEPDC5	HGNC:18423	ENSG00000100150	O75140	GATOR1 complex protein DEPDC5	gwas
ARHGEF10L	HGNC:25540	ENSG00000074964	Q9HCE6	Rho guanine nucleotide exchange factor 10-like protein	gwas
CWH43	HGNC:26133	ENSG00000109182	Q9H720	PGAP2-interacting protein	gwas
DNASE2B	HGNC:28875	ENSG00000137976	Q8WZ79	Deoxyribonuclease-2-beta	gwas
EFCAB14	HGNC:29051	ENSG00000159658	O75071	EF-hand calcium-binding domain-containing protein 14	gwas
AK9	HGNC:33814	ENSG00000155085	Q5TCS8	Adenylate kinase 9	gwas
EPHA7	HGNC:3390	ENSG00000135333	Q15375	Ephrin type-A receptor 7	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
ITPA	HGNC:6176	ENSG00000125877	Q9BY32	Inosine triphosphate pyrophosphatase	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCG2	Secretogranin-2	Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules.
SLC22A3	Solute carrier family 22 member 3	Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
DDRGK1	DDRGK domain-containing protein 1	Component of the UFM1 ribosome E3 ligase (UREL) complex, a multiprotein complex that catalyzes ufmylation of endoplasmic reticulum-docked proteins.
OLFM1	Noelin	Contributes to the regulation of axonal growth in the embryonic and adult central nervous system by inhibiting interactions between RTN4R and LINGO1.
IFNL1	Interferon lambda-1	Cytokine with antiviral, antitumour and immunomodulatory activities.
IFNL2	Interferon lambda-2	Cytokine with antiviral, antitumour and immunomodulatory activities.
IFNL3	Interferon lambda-3	Cytokine with antiviral, antitumour and immunomodulatory activities.
DEPDC5	GATOR1 complex protein DEPDC5	As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway.
ARHGEF10L	Rho guanine nucleotide exchange factor 10-like protein	Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RHOB and RHOC.
CWH43	PGAP2-interacting protein	Involved in lipid remodeling during GPI-anchor maturation.
DNASE2B	Deoxyribonuclease-2-beta	Hydrolyzes DNA under acidic conditions.
AK9	Adenylate kinase 9	Broad-specificity nucleoside phosphate kinase involved in cellular nucleotide homeostasis by catalyzing nucleoside-phosphate interconversions.
EPHA7	Ephrin type-A receptor 7	Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-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.
ITPA	Inosine triphosphate pyrophosphatase	Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2’-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and xanthosine 5’-triphosphate (XTP) to the…

Protein-family classification

Druggable: 6 · Difficult: 1 · 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
Transporter	1	4.6×	0.592
Antibody/Immunoglobulin	2	3.4×	0.592
Kinase	1	1.6×	0.602
Enzyme (other)	2	1.4×	0.602
Other/Unknown	10	1.1×	0.602
Scaffold/PPI	1	1.0×	0.637

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCG2	Other/Unknown	no		Granin, Chromogranin_CS, ScgII
SLC22A3	Transporter	yes		Orgcat_transp/SVOP, Sugar_transporter_CS, MFS
DDRGK1	Other/Unknown	no		DDRGK_dom-contain, WH-like_DNA-bd_sf, WH_DNA-bd_sf
OLFM1	Other/Unknown	no		Olfac-like_dom, Quino_amine_DH_bsu, Noelin_dom
IFNL1	Other/Unknown	no		INF_lambda, IFN-lambda_sf
IFNL2	Other/Unknown	no		INF_lambda, IFN-lambda_sf
IFNL3	Other/Unknown	no		INF_lambda, IFN-lambda_sf
DEPDC5	Other/Unknown	no		DEP_dom, IML1, WH-like_DNA-bd_sf
ARHGEF10L	Scaffold/PPI	no		DH_dom, PH-like_dom_sf, WD40/YVTN_repeat-like_dom_sf
CWH43	Other/Unknown	no		Endo/exonu/phosph_ase_sf, GPI-anchor_lipid_remodeler, PGAP2IP_TM_2nd
DNASE2B	Enzyme (other)	yes	3.1.22.1	DNase_II
EFCAB14	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EFCAB14
AK9	Other/Unknown	no		Adenylat/UMP-CMP_kin, AAA+_ATPase, P-loop_NTPase
EPHA7	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
HLA-DQA1	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
ITPA	Enzyme (other)	yes	3.6.1.66	RdgB/HAM1, ITPase, ITPase-like_fam

Expression context

Cohort genes with no expression data: 0.

14 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)	3
broad (>20)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	5
frontal pole	2
granulocyte	2
islet of Langerhans	1
lateral nuclear group of thalamus	1
type B pancreatic cell	1
ascending aorta	1
descending thoracic aorta	1
thoracic aorta	1
right adrenal gland	1
right adrenal gland cortex	1
tendon of biceps brachii	1
Brodmann (1909) area 10	1
middle temporal gyrus	1
skeletal muscle tissue of rectus abdominis	1
epithelium of nasopharynx	1
mucosa of paranasal sinus	1
primordial germ cell in gonad	1
middle frontal gyrus	1
paraflocculus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCG2	216	broad	marker	type B pancreatic cell, islet of Langerhans, lateral nuclear group of thalamus
SLC22A3	189	broad	marker	thoracic aorta, ascending aorta, descending thoracic aorta
DDRGK1	271	ubiquitous	marker	tendon of biceps brachii, right adrenal gland, right adrenal gland cortex
OLFM1	261	broad	marker	middle temporal gyrus, Brodmann (1909) area 10, frontal pole
IFNL1	18	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, granulocyte, skeletal muscle tissue of rectus abdominis
IFNL2	14	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, mucosa of paranasal sinus, epithelium of nasopharynx
IFNL3	15		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, granulocyte
DEPDC5	236	ubiquitous	marker	paraflocculus, frontal pole, middle frontal gyrus
ARHGEF10L	285	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
CWH43	155	tissue_specific	marker	tongue squamous epithelium, cervix squamous epithelium, gingival epithelium
DNASE2B	116	tissue_specific	marker	parotid gland, male germ line stem cell (sensu Vertebrata) in testis, saliva-secreting gland
EFCAB14	295	ubiquitous	marker	cardia of stomach, pylorus, medial globus pallidus
AK9	221	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, right uterine tube
EPHA7	184	broad	marker	cortical plate, lower esophagus muscularis layer, lower esophagus
HLA-DQA1	244	broad	marker	gall bladder, rectum, monocyte
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
ITPA	274	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDRGK1	4,153
AK9	2,977
EPHA7	2,865
ITPA	2,856
SLC22A3	1,542
OLFM1	1,416
DEPDC5	1,273
SCG2	1,130
IFNL1	980
IFNL3	810

Intra-cohort edges

A	B	Sources
AK9	ITPA	string_interaction
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
IFNL1	IFNL2	biogrid_interaction, intact, string_interaction
IFNL1	IFNL3	string_interaction
IFNL2	IFNL3	string_interaction
IFNL3	ITPA	string_interaction

Structural data

PDB: 10 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DQA1	P01909	28
DEPDC5	O75140	11
HLA-DQB1	P01920	10
DDRGK1	Q96HY6	8
EPHA7	Q15375	7
ITPA	Q9BY32	4
SLC22A3	O75751	3
IFNL3	Q8IZI9	3
OLFM1	Q99784	2
IFNL1	Q8IU54	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CWH43	Q9H720	91.45
DNASE2B	Q8WZ79	91.22
IFNL2	Q8IZJ0	84.12
AK9	Q5TCS8	73.70
ARHGEF10L	Q9HCE6	67.46
EFCAB14	O75071	67.45
SCG2	P13521	58.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 17 evidence-associated genes (13 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 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-20 family signaling	3	97.6×	1e-04	IFNL1, IFNL2, IFNL3
Metabolism of nucleotides	2	46.2×	0.018	AK9, ITPA
Drug ADME	2	35.1×	0.021	SLC22A3, ITPA
Abacavir transmembrane transport	1	175.7×	0.051	SLC22A3
Interferon gamma signaling	2	19.3×	0.051	HLA-DQA1, HLA-DQB1
Abacavir ADME	1	109.8×	0.057	SLC22A3
Nucleotide catabolism	1	97.6×	0.057	ITPA
Purine catabolism	1	79.9×	0.057	ITPA
Ribavirin ADME	1	79.9×	0.057	ITPA
RHOA GTPase cycle	2	11.5×	0.057	DDRGK1, ARHGEF10L
SLC-mediated transport of organic cations	1	58.6×	0.064	SLC22A3
R-HSA-549132	1	58.6×	0.064	SLC22A3
Translocation of ZAP-70 to Immunological synapse	1	48.8×	0.070	HLA-DQA1
Phosphorylation of CD3 and TCR zeta chains	1	41.8×	0.074	HLA-DQA1
Co-inhibition by PD-1	1	39.9×	0.074	HLA-DQA1
Other interleukin signaling	1	36.6×	0.076	IFNL1
EPHA-mediated growth cone collapse	1	29.3×	0.087	EPHA7
Interconversion of nucleotide di- and triphosphates	1	27.4×	0.087	AK9
Generation of second messenger molecules	1	26.6×	0.087	HLA-DQA1
Cell death signalling via NRAGE, NRIF and NADE	1	16.9×	0.124	ARHGEF10L
EPH-ephrin mediated repulsion of cells	1	16.9×	0.124	EPHA7
Amino acids regulate mTORC1	1	15.4×	0.125	DEPDC5
p75 NTR receptor-mediated signalling	1	14.4×	0.125	ARHGEF10L
NRAGE signals death through JNK	1	14.2×	0.125	ARHGEF10L
R-HSA-425366	1	13.9×	0.125	SLC22A3
EPH-Ephrin signaling	1	12.7×	0.131	EPHA7
RHOB GTPase cycle	1	11.9×	0.135	ARHGEF10L
RHOC GTPase cycle	1	11.3×	0.136	ARHGEF10L
Death Receptor Signaling	1	10.7×	0.136	ARHGEF10L
G alpha (12/13) signalling events	1	10.6×	0.136	ARHGEF10L

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
positive regulation of immune response	5	150.5×	2e-08	IFNL1, IFNL2, IFNL3, HLA-DQA1, HLA-DQB1
type III interferon-mediated signaling pathway	3	287.2×	9e-06	IFNL1, IFNL2, IFNL3
cell surface receptor signaling pathway via JAK-STAT	3	54.5×	0.001	IFNL1, IFNL2, IFNL3
cellular response to virus	3	37.6×	0.002	IFNL1, IFNL2, IFNL3
peptide antigen assembly with MHC class II protein complex	2	131.7×	0.003	HLA-DQA1, HLA-DQB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	2	68.0×	0.010	HLA-DQA1, HLA-DQB1
positive regulation of T cell activation	2	55.4×	0.012	HLA-DQA1, HLA-DQB1
ITP catabolic process	1	1053.2×	0.014	ITPA
deoxyribonucleoside triphosphate catabolic process	1	1053.2×	0.014	ITPA
positive regulation of I-kappaB phosphorylation	1	1053.2×	0.014	DDRGK1
regulation of protein autophosphorylation	1	526.6×	0.018	EPHA7
negative regulation of memory T cell differentiation	1	526.6×	0.018	IFNL1
CDP biosynthetic process	1	526.6×	0.018	AK9
epinephrine uptake	1	526.6×	0.018	SLC22A3
protein localization to extracellular region	1	526.6×	0.018	CWH43
defense response to virus	3	13.0×	0.018	IFNL1, IFNL2, IFNL3
histamine transport	1	351.1×	0.020	SLC22A3
purine-containing compound transmembrane transport	1	351.1×	0.020	SLC22A3
positive regulation of reticulophagy	1	351.1×	0.020	DDRGK1
positive regulation of protein localization to endoplasmic reticulum	1	351.1×	0.020	DDRGK1
histamine metabolic process	1	263.3×	0.020	SLC22A3
peptide secretion	1	263.3×	0.020	CWH43
atrioventricular valve formation	1	263.3×	0.020	OLFM1
spermidine transport	1	263.3×	0.020	SLC22A3
obsolete epinephrine transport	1	263.3×	0.020	SLC22A3
histamine uptake	1	263.3×	0.020	SLC22A3
positive regulation of plasma cell differentiation	1	263.3×	0.020	DDRGK1
obsolete positive regulation of proteolysis involved in protein catabolic process	1	263.3×	0.020	DDRGK1
UDP biosynthetic process	1	210.7×	0.020	AK9
obsolete serotonin transport	1	210.7×	0.020	SLC22A3

Therapeutics

Drugs indicated or in trials for this disease

18 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Boceprevir	Approved (phase 4)
Elbasvir	Approved (phase 4)
Glecaprevir	Approved (phase 4)
Grazoprevir Anhydrous	Approved (phase 4)
INTERFERON ALFA-2B	Approved (phase 4)
INTERFERON ALFACON-1	Approved (phase 4)
Ledipasvir	Approved (phase 4)
Ombitasvir	Approved (phase 4)
PEGINTERFERON ALFA-2A	Approved (phase 4)
PEGINTERFERON ALFA-2B	Approved (phase 4)
Paritaprevir	Approved (phase 4)
Pibrentasvir	Approved (phase 4)
Ribavirin	Approved (phase 4)
Ritonavir	Approved (phase 4)
Sofosbuvir	Approved (phase 4)
Telaprevir	Approved (phase 4)
Velpatasvir	Approved (phase 4)
Voxilaprevir	Approved (phase 4)

47 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
ALBINTERFERON ALFA-2B	Phase 3
Alisporivir	Phase 3
Amantadine	Phase 3
Asunaprevir	Phase 3
Bulevirtide	Phase 3
Cyclosporine	Phase 3
Daclatasvir	Phase 3
Danoprevir	Phase 3
Dasabuvir	Phase 3
Deleobuvir	Phase 3
Eltrombopag	Phase 3
Epoetin Beta	Phase 3
Ergocalciferol	Phase 3
Faldaprevir	Phase 3
Infliximab	Phase 3
Interferon Alfa	Phase 3
Irbesartan	Phase 3
PEGINTERFERON LAMBDA-1A	Phase 3
POLYETHYLENE GLYCOL 3350	Phase 3
Paroxetine	Phase 3
ROPEGINTERFERON ALFA-2B	Phase 3
Simeprevir	Phase 3
Thymalfasin	Phase 3
Ursodiol	Phase 3
Vaniprevir	Phase 3
Yimitasvir	Phase 3
Beclabuvir	Phase 2
Colchicine	Phase 2
Desvenlafaxine	Phase 2
Doconexent	Phase 2
Ezetimibe	Phase 2
Fluvastatin	Phase 2
Furaprevir	Phase 2
INTERFERON ALFA-2A	Phase 2
INTERFERON GAMMA-1B	Phase 2
Icosapent	Phase 2
Interferon	Phase 2
Methionine	Phase 2
Milk Thistle	Phase 2
Narlaprevir	Phase 2
Nitazoxanide	Phase 2
Pioglitazone	Phase 2
Silybin A	Phase 2
Tacrolimus Anhydrous	Phase 2
Taribavirin	Phase 2
Tenofovir Disoproxil	Phase 2
Valacyclovir	Phase 2

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 15

Druggability breadth: 5 of 17 evidence-associated genes (29%) 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
SLC22A3	PROGESTERONE
EPHA7	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPHA7	29	4
SLC22A3	20	4
SCG2	0	0
DDRGK1	0	0
OLFM1	0	0
IFNL1	0	0
IFNL2	0	0
IFNL3	0	0
DEPDC5	0	0
ARHGEF10L	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PROGESTERONE	4	SLC22A3
COLCHICINE	4	SLC22A3
IMIPRAMINE	4	SLC22A3
CLONIDINE	4	SLC22A3
ESTRADIOL	4	SLC22A3
IBRUTINIB	4	SLC22A3
PRAZOSIN	4	SLC22A3
NILOTINIB	4	SLC22A3
BITHIONOL	4	SLC22A3
ONDANSETRON	4	SLC22A3
IRINOTECAN	4	SLC22A3
PENTAMIDINE	4	SLC22A3
MITOXANTRONE	4	SLC22A3
DESIPRAMINE	4	SLC22A3
PHENOXYBENZAMINE	4	SLC22A3
CHLORHEXIDINE	4	SLC22A3
FAMOTIDINE	4	SLC22A3
IMATINIB	4	SLC22A3
FEDRATINIB	4	EPHA7
SORAFENIB	4	EPHA7
VANDETANIB	4	EPHA7
GILTERITINIB	4	EPHA7
SUNITINIB	4	EPHA7
ERLOTINIB	4	EPHA7
QUIZARTINIB	4	EPHA7
CRIZOTINIB	4	EPHA7
CORTICOSTERONE	3	SLC22A3
LINIFANIB	3	EPHA7
CANERTINIB	3	EPHA7
TESEVATINIB	3	EPHA7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
EPHA7	231	Binding:231
SLC22A3	33	Binding:17, Functional:11, ADMET:5
ITPA	8	Binding:8
HLA-DQA1	2	Binding:2
DDRGK1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DNASE2B	3.1.22.1	deoxyribonuclease II
EPHA7	2.7.10.1	receptor protein-tyrosine kinase
ITPA	3.6.1.66, 3.6.1.9	XTP/dITP diphosphatase, nucleotide diphosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EPHA7	231

Pharmacogenomics

Cohort genes with a PharmGKB record: 17; 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)
PROGESTERONE	4	SLC22A3
COLCHICINE	4	SLC22A3
IMIPRAMINE	4	SLC22A3
CLONIDINE	4	SLC22A3
ESTRADIOL	4	SLC22A3
IBRUTINIB	4	SLC22A3
PRAZOSIN	4	SLC22A3
NILOTINIB	4	SLC22A3
BITHIONOL	4	SLC22A3
ONDANSETRON	4	SLC22A3
IRINOTECAN	4	SLC22A3
PENTAMIDINE	4	SLC22A3
MITOXANTRONE	4	SLC22A3
DESIPRAMINE	4	SLC22A3
PHENOXYBENZAMINE	4	SLC22A3
CHLORHEXIDINE	4	SLC22A3
FAMOTIDINE	4	SLC22A3
IMATINIB	4	SLC22A3
FEDRATINIB	4	EPHA7
SORAFENIB	4	EPHA7
VANDETANIB	4	EPHA7
GILTERITINIB	4	EPHA7
SUNITINIB	4	EPHA7
ERLOTINIB	4	EPHA7
QUIZARTINIB	4	EPHA7
CRIZOTINIB	4	EPHA7
CORTICOSTERONE	3	SLC22A3
LINIFANIB	3	EPHA7
CANERTINIB	3	EPHA7
TESEVATINIB	3	EPHA7

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SLC22A3, EPHA7
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	HLA-DQA1, HLA-DQB1, ITPA
D	Druggable family + AlphaFold only, no drug	1	DNASE2B
E	Difficult family or no structure, no drug	11	SCG2, DDRGK1, OLFM1, IFNL1, IFNL2, IFNL3, DEPDC5, ARHGEF10L, CWH43, EFCAB14 (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SCG2	0	—
DDRGK1	1	—
OLFM1	0	—
IFNL1	0	—
IFNL2	0	—
IFNL3	0	—
DEPDC5	0	—
ARHGEF10L	0	—
CWH43	0	—
DNASE2B	0	—
EFCAB14	0	—
AK9	0	—
HLA-DQA1	2	—
HLA-DQB1	0	—
ITPA	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 811.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	242
PHASE2	168
PHASE3	146
PHASE4	130
PHASE1	76
PHASE1/PHASE2	29
PHASE2/PHASE3	17
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03520660	PHASE4	ACTIVE_NOT_RECRUITING	People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
NCT05140941	PHASE4	ACTIVE_NOT_RECRUITING	Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
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
NCT00077636	PHASE4	COMPLETED	ACCELERATE Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Combination With COPEGUS (Ribavirin) in Interferon-Naive Patients With Chronic Hepatitis C (CHC) Infection.
NCT00077649	PHASE4	COMPLETED	A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Combination With COPEGUS (Ribavirin) in Interferon-Naive Patients With Chronic Hepatitis C Infection (CHC).
NCT00087568	PHASE4	COMPLETED	A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Combination With Ribavirin in Patients With Chronic Hepatitis C (CHC) Previously Treated With PEG-Intron + Ribavirin
NCT00087594	PHASE4	COMPLETED	A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Combination With Copegus (Ribavirin) in Patients With Chronic Hepatitis C (CHC) Enrolled in a Methadone Maintenance Treatment Program.
NCT00087607	PHASE4	COMPLETED	Peak Study - A Study of Pegasys (Peginterferon Alfa-2a (40KD)) in Combination With Copegus (Ribavirin) in Interferon-Naive Patients With Chronic Hepatitis C (CHC).
NCT00087633	PHASE4	COMPLETED	PHOENIX Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) and COPEGUS (Ribavirin) Administered After Liver Transplantation for Hepatitis C.
NCT00087646	PHASE4	COMPLETED	REPEAT Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Therapy in Combination With COPEGUS (Ribavirin) in Patients With Chronic Hepatitis C (CHC) Who Did Not Respond to Previous PegIntron (Peginterferon Alfa-2b (12KD))/Ribavirin Combination Therapy
NCT00107653	PHASE4	COMPLETED	Latino Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) and COPEGUS (Ribavirin) in Treatment-Naive Patients With Chronic Hepatitis C-Genotype 1.
NCT00127777	PHASE4	UNKNOWN	Peginterferon Alfa-2a, Ribavirin, Amantadine/Placebo in Hepatitis C Virus (HCV)-Genotype-1-Infection (PRAMA)
NCT00172809	PHASE4	COMPLETED	Interferon Treatment for Patients With Chronic Hepatitis C and End Stage Renal Disease
NCT00189163	PHASE4	COMPLETED	Pioglitazone in Hepatitis C
NCT00192647	PHASE4	COMPLETED	A Study of Induction Dosing With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C (CHC) Genotype 1 Infection
NCT00202839	PHASE4	COMPLETED	Peg-Intron/Ribavirin in G 1 HCV for Non-Extended Versus 24 Week Extended Treatment After 24 Weeks (Study P04144)(COMPLETED)
NCT00209898	PHASE4	TERMINATED	Hepatitis C Treatment of Inmates
NCT00245414	PHASE4	COMPLETED	Trial of Pegasys® in Patients With Chronic Hepatitis C
NCT00255008	PHASE4	TERMINATED	Peg-Intron and Rebetol Therapy in Treatment of Naive Hepatitis C Patients: A Comparison of Race and Genotype on Treatment Outcome (Study P04212)
NCT00255034	PHASE4	TERMINATED	Effects of 48 Weeks Versus 24 Weeks of Therapy With Peg-Intron/Ribavirin in Patients With Chronic Hepatitis C, Genotype 3 (Study P04143)(TERMINATED)
NCT00279565	PHASE4	TERMINATED	Buprenorphine Versus Methadone Maintenance in Hepatitis C Patients Receiving Peg-Intron and Rebetol (Study P04279)(TERMINATED)
NCT00298714	PHASE4	COMPLETED	Effects of Losartan on Hepatic Fibrogenesis in Chronic Hepatitis C
NCT00351403	PHASE4	COMPLETED	Individually Adapted Therapy Duration for the Treatment of Chronic Hepatitis C Genotype 1 Infection
NCT00351871	PHASE4	COMPLETED	Influence of Marker of Insulin Resistance Upon Hepatitis C Virus (HCV) Treatment Responses to PEG Intron and Rebetol Therapy
NCT00353418	PHASE4	COMPLETED	A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Plus COPEGUS (Ribavirin) in Patients With Chronic Hepatitis C (CHC) Genotype 1 and Human Immunodeficiency Virus-1 (HIV-1) Co-infection
NCT00370617	PHASE4	UNKNOWN	Pegylated-Interferon and Ribavirin Plus Metformin in the Treatment of Chronic HCV Infection and Insulin Resistance
NCT00375661	PHASE4	COMPLETED	Low-dose Peg-interferon Plus Ribavirin (IFN/RBV) for Prevention of Hepatocellular Carcinoma (HCC) Recurrence in Patients Who Had Surgery to Remove Primary HCC
NCT00394277	PHASE4	COMPLETED	A Study of Induction Dosing With PEGASYS (Peginterferon Alfa-2a [40KD]) Plus Copegus in Treatment-Naive Patients With Chronic Hepatitis C
NCT00412334	PHASE4	COMPLETED	SYREN Study: A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Plus Copegus (Ribavirin) in Non-Responder Patients With Chronic Hepatitis C (CHC) Genotype 1.
NCT00474955	PHASE4	COMPLETED	A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) in Patients With Chronic Hepatitis C and Chronic Renal Failure.
NCT00475072	PHASE4	COMPLETED	A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Plus Ribavirin in Hemophiliac Patients With Chronic Hepatitis C.
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
NCT00493805	PHASE4	TERMINATED	Study of Response in Chronic Hepatitis C (CHC) Participants Genotype 1 With Insulin Resistance and Prolonged Treatment Duration in Late Responders (P04823/MK-4031-303)
NCT00495131	PHASE4	COMPLETED	Randomized Trial of 24 or 48 Weeks of Peginterferon Alfa-2a Plus Ribavirin for HCV Genotype 1-infected Patients
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RIBAVIRIN	4	297
PEGINTERFERON ALFA-2A	4	39
SIMEPREVIR	4	27
TELAPREVIR	4	27
PEGINTERFERON ALFA-2B	4	25
RITONAVIR	4	25
BOCEPREVIR	4	24
DACLATASVIR	4	23
SOFOSBUVIR	4	23
GRAZOPREVIR ANHYDROUS	4	18
PARITAPREVIR	4	18
OMBITASVIR	4	17
DASABUVIR	4	13
GLECAPREVIR	4	13
LEDIPASVIR	4	12
PIBRENTASVIR	4	12
VELPATASVIR	4	11
NITAZOXANIDE	4	7
ASUNAPREVIR	4	6
AMANTADINE	4	4
ELBASVIR	4	4
ELTROMBOPAG	4	4
INTERFERON ALFA-2A	4	3
METFORMIN	4	3
PIOGLITAZONE	4	3
ROPEGINTERFERON ALFA-2B	4	3
BETAINE	4	2
CYANOCOBALAMIN	4	2
VOXILAPREVIR	4	2
ACARBOSE	4	1