Gallbladder disease 1

Summary

Gallbladder disease 1 (MONDO:0010939) is a disease caused by ABCB4 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: ABCB4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 311
• Phenotypes (HPO): 19
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0001406	Intrahepatic cholestasis	Very frequent (80-99%)
HP:0011848	Abdominal colic	Very frequent (80-99%)
HP:0001081	Cholelithiasis	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0025502	Overweight	Frequent (30-79%)
HP:0030948	Elevated gamma-glutamyltransferase level	Frequent (30-79%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001082	Cholecystitis	Occasional (5-29%)
HP:0001402	Hepatocellular carcinoma	Occasional (5-29%)
HP:0001513	Obesity	Occasional (5-29%)
HP:0001733	Pancreatitis	Occasional (5-29%)
HP:0002896	Neoplasm of the liver	Occasional (5-29%)
HP:0003124	Hypercholesterolemia	Occasional (5-29%)
HP:0005230	Biliary tract obstruction	Occasional (5-29%)
HP:0030151	Cholangitis	Occasional (5-29%)
HP:0000819	Diabetes mellitus	Very rare (<1-4%)
HP:0002613	Biliary cirrhosis	Very rare (<1-4%)
HP:0030991	Sclerosing cholangitis	Very rare (<1-4%)
HP:0100523	Liver abscess	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	gallbladder disease 1
Mondo ID	MONDO:0010939
OMIM	600803
Orphanet	69663
ICD-11	1261516421
SNOMED CT	715577009
UMLS	C2609268
MedGen	760527
GARD	0016683
MedDRA	10068936
Is cancer (heuristic)	no

Also known as: ABCB4 gene mutation-associated cholelithiasis · cholelithiasis with ABCB4 gene mutation · cholelithiasis, low phospholipid-associated · gallbladder disease 1 · gallbladder disease type 1 · GBD1 · low phospholipid associated cholelithiasis · LPAC

Data availability: 311 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › biliary tract disorder › cholelithiasis › gallbladder disease 1

Related subtypes (3): cholecystolithiasis, choledocholithiasis, primary intrahepatic lithiasis

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

311 retrieved; paginated sample, class counts are floors:

157 uncertain significance, 35 pathogenic, 34 conflicting classifications of pathogenicity, 25 likely benign, 19 pathogenic/likely pathogenic, 17 likely pathogenic, 15 benign, 9 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13687	NM_000443.4(ABCB4):c.2869C>T (p.Arg957Ter)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13690	NM_000443.4(ABCB4):c.959C>T (p.Ser320Phe)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13693	NM_000443.4(ABCB4):c.1328_1329delinsCAA (p.Gln443fs)	ABCB4	Pathogenic	criteria provided, single submitter
1685489	NM_000443.4(ABCB4):c.2682+1G>A	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685491	NM_000443.4(ABCB4):c.984T>G (p.Tyr328Ter)	ABCB4	Pathogenic	criteria provided, multiple submitters, no conflicts
194708	NM_000443.4(ABCB4):c.2211+1G>A	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
194709	NM_000443.4(ABCB4):c.2177C>T (p.Pro726Leu)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2628376	NM_000443.4(ABCB4):c.1216C>T (p.Arg406Ter)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2635175	NM_000443.4(ABCB4):c.286+1G>A	ABCB4	Pathogenic	criteria provided, multiple submitters, no conflicts
2687818	NM_000443.4(ABCB4):c.88_91del (p.Lys30fs)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2735039	NM_000443.4(ABCB4):c.3541C>T (p.Gln1181Ter)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2735040	NM_000443.4(ABCB4):c.3349C>T (p.Gln1117Ter)	ABCB4	Pathogenic	criteria provided, multiple submitters, no conflicts
2805923	NM_000443.4(ABCB4):c.1318C>T (p.Gln440Ter)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3032272	NM_000443.4(ABCB4):c.1371del (p.Gln458fs)	ABCB4	Pathogenic	criteria provided, multiple submitters, no conflicts
3242002	NM_000443.4(ABCB4):c.202G>A (p.Gly68Arg)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3594921	NM_000443.4(ABCB4):c.3139_3141delinsCC (p.Ala1047fs)	ABCB4	Pathogenic	criteria provided, multiple submitters, no conflicts
372802	NM_000443.4(ABCB4):c.526C>T (p.Arg176Trp)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3773726	NM_000443.4(ABCB4):c.1939G>T (p.Glu647Ter)	ABCB4	Pathogenic	criteria provided, single submitter
4536822	NM_000443.4(ABCB4):c.1633C>T (p.Arg545Cys)	ABCB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4846337	NM_000443.4(ABCB4):c.1356+2T>C	ABCB4	Pathogenic	criteria provided, single submitter
4846366	NM_000443.4(ABCB4):c.344+2dup	ABCB4	Pathogenic	criteria provided, single submitter
4846391	NM_000443.4(ABCB4):c.784dup (p.Ala262fs)	ABCB4	Pathogenic	criteria provided, single submitter
4846439	NM_000443.4(ABCB4):c.2662G>T (p.Glu888Ter)	ABCB4	Pathogenic	criteria provided, single submitter
4846453	NM_000443.4(ABCB4):c.2273dup (p.Phe760fs)	ABCB4	Pathogenic	criteria provided, single submitter
4846505	NM_000443.4(ABCB4):c.1621A>T (p.Ile541Phe)	ABCB4	Pathogenic	criteria provided, single submitter
4846555	NM_000443.4(ABCB4):c.1A>T (p.Met1Leu)	ABCB4	Pathogenic	criteria provided, single submitter
4846557	NM_000443.4(ABCB4):c.900_901del (p.Met301fs)	ABCB4	Pathogenic	criteria provided, single submitter
4846570	NM_000443.4(ABCB4):c.2078del (p.Pro693fs)	ABCB4	Pathogenic	criteria provided, single submitter
4846575	NM_000443.4(ABCB4):c.3316del (p.Gln1106fs)	ABCB4	Pathogenic	criteria provided, single submitter
4846596	NM_000443.4(ABCB4):c.3559C>T (p.Arg1187Ter)	ABCB4	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
ABCB4	Definitive	Semidominant	gallbladder disease 1	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCB4	Orphanet:69663	Low phospholipid-associated cholelithiasis
ABCB4	Orphanet:69665	Intrahepatic cholestasis of pregnancy
ABCB4	Orphanet:79305	Progressive familial intrahepatic cholestasis type 3

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
ABCB4	HGNC:45	ENSG00000005471	P21439	Phosphatidylcholine translocator ABCB4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCB4	Phosphatidylcholine translocator ABCB4	Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion.

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)
ABCB4	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
oocyte	1
right lobe of liver	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCB4	188	broad	marker	right lobe of liver, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCB4	2,333

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCB4	P21439	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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 ABCB4 causes PFIC3, ICP3 and GBD1	1	11420.0×	9e-04	ABCB4
ABC transporter disorders	1	439.2×	0.011	ABCB4
Regulation of lipid metabolism by PPARalpha	1	141.0×	0.016	ABCB4
Disorders of transmembrane transporters	1	139.3×	0.016	ABCB4
ABC-family protein mediated transport	1	121.5×	0.016	ABCB4
PPARA activates gene expression	1	94.4×	0.018	ABCB4
Metabolism of lipids	1	31.6×	0.045	ABCB4
Transport of small molecules	1	25.1×	0.050	ABCB4
Disease	1	13.1×	0.085	ABCB4
Metabolism	1	11.6×	0.086	ABCB4

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
response to fenofibrate	1	8426.0×	7e-04	ABCB4
positive regulation of phospholipid translocation	1	4213.0×	7e-04	ABCB4
cellular response to bile acid	1	4213.0×	7e-04	ABCB4
bile acid secretion	1	3370.4×	7e-04	ABCB4
positive regulation of cholesterol transport	1	2407.4×	7e-04	ABCB4
positive regulation of phospholipid transport	1	2407.4×	7e-04	ABCB4
phospholipid translocation	1	624.1×	0.002	ABCB4
lipid homeostasis	1	337.0×	0.004	ABCB4
transmembrane transport	1	168.5×	0.007	ABCB4
lipid metabolic process	1	91.6×	0.011	ABCB4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCB4	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BMS-986020	2	ABCB4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABCB4	4	ADMET:3, Binding:1

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

1 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)
BMS-986020	2	ABCB4

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	1	ABCB4
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05961826	Not specified	ACTIVE_NOT_RECRUITING	COLPAC (RaDiCo Cohort) (RaDiCo-COLPAC)