Benign recurrent intrahepatic cholestasis type 2

Summary

Benign recurrent intrahepatic cholestasis type 2 (MONDO:0011559) is a disease caused by ABCB11 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ABCB11 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 189

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	benign recurrent intrahepatic cholestasis type 2
Mondo ID	MONDO:0011559
MeSH	C535934
OMIM	605479
Orphanet	99961
DOID	DOID:0070232
UMLS	C2608083
MedGen	435857
GARD	0010029
Is cancer (heuristic)	no

Also known as: benign recurrent intrahepatic cholestasis 2 · Bric type 2 · BRIC2 · cholestasis, benign recurrent intrahepatic 2 · cholestasis, benign recurrent intrahepatic, 2 · cholestasis, benign recurrent intrahepatic, type 2 · mild ABCB11 deficiency · recurrent familial intrahepatic cholestasis 2

Data availability: 189 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › liver disorder › familial intrahepatic cholestasis › benign recurrent intrahepatic cholestasis › benign recurrent intrahepatic cholestasis type 2

Related subtypes (1): benign recurrent intrahepatic cholestasis type 1

Subtypes (1): progressive familial intrahepatic cholestasis type 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

189 retrieved; paginated sample, class counts are floors:

44 pathogenic/likely pathogenic, 43 likely pathogenic, 40 conflicting classifications of pathogenicity, 31 pathogenic, 14 benign, 14 uncertain significance, 2 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028652	NM_003742.4(ABCB11):c.2488del (p.Arg830fs)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
1070201	NM_003742.4(ABCB11):c.2319dup (p.Phe774fs)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070782	NM_003742.4(ABCB11):c.1429G>T (p.Gly477Ter)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075698	NM_003742.4(ABCB11):c.3772C>T (p.Gln1258Ter)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076790	NM_003742.4(ABCB11):c.3491del (p.Val1164fs)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
1076791	NM_003742.4(ABCB11):c.3458G>A (p.Arg1153His)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1383688	NM_003742.4(ABCB11):c.1415A>G (p.Tyr472Cys)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1410817	NM_003742.4(ABCB11):c.3703C>T (p.Arg1235Ter)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
1444576	NM_003742.4(ABCB11):c.3804del (p.Thr1269fs)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1446289	NM_003742.4(ABCB11):c.1621A>C (p.Ile541Leu)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1446319	NM_003742.4(ABCB11):c.1243C>T (p.Arg415Ter)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
1446335	NM_003742.4(ABCB11):c.499G>A (p.Ala167Thr)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453316	NM_003742.4(ABCB11):c.3904G>T (p.Glu1302Ter)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
1453324	NM_003742.4(ABCB11):c.1941del (p.Gly648fs)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
1456442	NM_003742.4(ABCB11):c.959_960del (p.Ile320fs)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526234	NM_003742.4(ABCB11):c.611+1G>A	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
2674704	NM_003742.4(ABCB11):c.65C>G (p.Ser22Ter)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2674786	NM_003742.4(ABCB11):c.1685G>A (p.Gly562Asp)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676819	NM_003742.4(ABCB11):c.1636C>T (p.Gln546Ter)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678310	NM_003742.4(ABCB11):c.2542del (p.Asp848fs)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679521	NM_003742.4(ABCB11):c.1081C>T (p.Gln361Ter)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
2679806	NM_003742.4(ABCB11):c.2316T>G (p.Tyr772Ter)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679906	NM_003742.4(ABCB11):c.2178+1G>T	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
2679946	NM_003742.4(ABCB11):c.779G>A (p.Gly260Asp)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680109	NM_003742.4(ABCB11):c.1029dup (p.Gly344fs)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680196	NM_003742.4(ABCB11):c.567G>A (p.Trp189Ter)	ABCB11	Pathogenic	criteria provided, multiple submitters, no conflicts
2680334	NM_003742.4(ABCB11):c.2815-2A>G	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680384	NM_003742.4(ABCB11):c.1198-1G>C	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680443	NM_003742.4(ABCB11):c.2343+1G>C	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680470	NM_003742.4(ABCB11):c.884dup (p.Gly296fs)	ABCB11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ABCB11	Definitive	Autosomal recessive	progressive familial intrahepatic cholestasis type 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCB11	Orphanet:69665	Intrahepatic cholestasis of pregnancy
ABCB11	Orphanet:79304	Progressive familial intrahepatic cholestasis type 2
ABCB11	Orphanet:99961	Benign recurrent intrahepatic cholestasis type 2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABCB11	HGNC:42	ENSG00000073734	O95342	Bile salt export pump	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCB11	Bile salt export pump	Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeosta…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCB11	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
liver	1
right lobe of liver	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCB11	125	tissue_specific	marker	right lobe of liver, liver, thymus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCB11	2,407

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCB11	O95342	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 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
Defective ABCB11 causes PFIC2 and BRIC2	1	11420.0×	1e-03	ABCB11
Recycling of bile acids and salts	1	601.0×	0.004	ABCB11
Bile acid and bile salt metabolism	1	496.5×	0.004	ABCB11
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	1	456.8×	0.004	ABCB11
ABC transporter disorders	1	439.2×	0.004	ABCB11
Synthesis of bile acids and bile salts	1	407.9×	0.004	ABCB11
Disorders of transmembrane transporters	1	139.3×	0.010	ABCB11
Metabolism of steroids	1	137.6×	0.010	ABCB11
Metabolism of lipids	1	31.6×	0.039	ABCB11
Disease	1	13.1×	0.084	ABCB11
Metabolism	1	11.6×	0.086	ABCB11

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
canalicular bile acid transport	1	16852.0×	5e-04	ABCB11
positive regulation of bile acid secretion	1	16852.0×	5e-04	ABCB11
xenobiotic export from cell	1	5617.3×	7e-04	ABCB11
obsolete regulation of bile acid metabolic process	1	5617.3×	7e-04	ABCB11
regulation of fatty acid beta-oxidation	1	2808.7×	0.001	ABCB11
bile acid metabolic process	1	991.3×	0.002	ABCB11
phospholipid homeostasis	1	991.3×	0.002	ABCB11
xenobiotic transmembrane transport	1	936.2×	0.002	ABCB11
bile acid and bile salt transport	1	648.1×	0.003	ABCB11
bile acid biosynthetic process	1	624.1×	0.003	ABCB11
lipid homeostasis	1	337.0×	0.004	ABCB11
fatty acid metabolic process	1	193.7×	0.007	ABCB11
transmembrane transport	1	168.5×	0.007	ABCB11
cholesterol homeostasis	1	156.0×	0.007	ABCB11
xenobiotic metabolic process	1	149.1×	0.007	ABCB11
protein ubiquitination	1	41.4×	0.024	ABCB11

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
ABCB11	TELMISARTAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCB11	327	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TELMISARTAN	4	ABCB11
BEXAROTENE	4	ABCB11
PROGESTERONE	4	ABCB11
CLOTRIMAZOLE	4	ABCB11
LATANOPROST	4	ABCB11
SIMVASTATIN	4	ABCB11
METHYSERGIDE	4	ABCB11
VALSARTAN	4	ABCB11
BROMFENAC	4	ABCB11
CLOPIDOGREL BISULFATE	4	ABCB11
DIBUCAINE	4	ABCB11
VALRUBICIN	4	ABCB11
RIMONABANT	4	ABCB11
ARIPIPRAZOLE	4	ABCB11
DICYCLOMINE	4	ABCB11
ACITRETIN	4	ABCB11
TELITHROMYCIN	4	ABCB11
EZETIMIBE	4	ABCB11
SAQUINAVIR	4	ABCB11
CLOBETASOL PROPIONATE	4	ABCB11
AMPRENAVIR	4	ABCB11
MOMETASONE FUROATE	4	ABCB11
NORETHINDRONE	4	ABCB11
ATAZANAVIR	4	ABCB11
FEBUXOSTAT	4	ABCB11
PONATINIB	4	ABCB11
TETRABENAZINE	4	ABCB11
CELECOXIB	4	ABCB11
VILANTEROL	4	ABCB11
EXEMESTANE	4	ABCB11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABCB11	85	Binding:37, ADMET:31, Functional:13, Toxicity:4

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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)
TELMISARTAN	4	ABCB11
BEXAROTENE	4	ABCB11
PROGESTERONE	4	ABCB11
CLOTRIMAZOLE	4	ABCB11
LATANOPROST	4	ABCB11
SIMVASTATIN	4	ABCB11
METHYSERGIDE	4	ABCB11
VALSARTAN	4	ABCB11
BROMFENAC	4	ABCB11
CLOPIDOGREL BISULFATE	4	ABCB11
DIBUCAINE	4	ABCB11
VALRUBICIN	4	ABCB11
RIMONABANT	4	ABCB11
ARIPIPRAZOLE	4	ABCB11
DICYCLOMINE	4	ABCB11
ACITRETIN	4	ABCB11
TELITHROMYCIN	4	ABCB11
EZETIMIBE	4	ABCB11
SAQUINAVIR	4	ABCB11
CLOBETASOL PROPIONATE	4	ABCB11
AMPRENAVIR	4	ABCB11
MOMETASONE FUROATE	4	ABCB11
NORETHINDRONE	4	ABCB11
ATAZANAVIR	4	ABCB11
FEBUXOSTAT	4	ABCB11
PONATINIB	4	ABCB11
TETRABENAZINE	4	ABCB11
CELECOXIB	4	ABCB11
VILANTEROL	4	ABCB11
EXEMESTANE	4	ABCB11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCB11
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.