hepatitis C induced liver cirrhosis

Summary

hepatitis C induced liver cirrhosis (MONDO:0005448) is a disease with 2 cohort genes (5 GWAS associations across 1 studies).

At a glance

• Cohort genes: 2
• GWAS associations: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hepatitis C induced liver cirrhosis
Mondo ID	MONDO:0005448
EFO	EFO:0005129
UMLS	C4763867
MedGen	1674707
Is cancer (heuristic)	no

Data availability: 5 GWAS associations (1 study).

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › liver disorder › cirrhosis of liver › hepatitis C induced liver cirrhosis

Related subtypes (2): alcoholic liver cirrhosis, cirrhosis, familial

Genetics & variants

GWAS landscape

5 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs910049	9e-11	TSBP1, TSBP1-AS1	A	1.46
rs9405098	1e-10	TSBP1-AS1 - HLA-DRA	A	1.37
rs3135363	1e-10	TSBP1-AS1 - HLA-DRA	C	1.37
rs3129860	1e-09	TSBP1-AS1 - HLA-DRA	A	1.36
rs3817963	1e-08	BTNL2, TSBP1-AS1	A	1.3

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST001815	Urabe Y	2013	682	1,045	A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	5

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	4
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs910049	6	32347950	T>A,C,G	0.142	intron_variant	TSBP1, TSBP1-AS1	9e-11	Tier 4: intronic/intergenic
rs9405098	6	32411959	G>A,C	0.253	intergenic_variant	TSBP1-AS1 - HLA-DRA	1e-10	Tier 4: intronic/intergenic
rs3135363	6	32421871	A>C,G,T	0.298	intron_variant	TSBP1-AS1 - HLA-DRA	1e-10	Tier 4: intronic/intergenic
rs3129860	6	32433302	A>G,T	0.231	intron_variant	TSBP1-AS1 - HLA-DRA	1e-09	Tier 4: intronic/intergenic
rs3817963	6	32400310	T>A,C,G	0.315	intron_variant	BTNL2, TSBP1-AS1	1e-08	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BTNL2	Orphanet:797	Sarcoidosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
TSBP1	HGNC:13922	ENSG00000204296	Q5SRN2	Testis-expressed basic protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
TSBP1	Other/Unknown	no		TSBP1

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	1
sural nerve	1
ventricular zone	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BTNL2	106		yes	sural nerve, ventricular zone, primordial germ cell in gonad
TSBP1	58	tissue_specific	yes	left testis, testis, right testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BTNL2	998
TSBP1	362

Intra-cohort edges

A	B	Sources
BTNL2	TSBP1	string_interaction

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BTNL2	Q9UIR0	85.97
TSBP1	Q5SRN2	45.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Butyrophilin (BTN) family interactions	1	878.5×	0.003	BTNL2
Adaptive Immune System	1	29.8×	0.050	BTNL2
Immune System	1	13.0×	0.077	BTNL2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 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 interleukin-2 production	1	468.1×	0.005	BTNL2
negative regulation of T cell receptor signaling pathway	1	366.4×	0.005	BTNL2
positive regulation of T cell proliferation	1	259.3×	0.005	BTNL2
regulation of cytokine production	1	247.8×	0.005	BTNL2
T cell receptor signaling pathway	1	151.8×	0.007	BTNL2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BTNL2	0	0
TSBP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	BTNL2
E	Difficult family or no structure, no drug	1	TSBP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BTNL2	0	—
TSBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.