LSR

Summary

LSR (lipolysis stimulated lipoprotein receptor, HGNC:29572) is a protein-coding gene on chromosome 19q13.12, encoding Lipolysis-stimulated lipoprotein receptor (Q86X29). Probable role in the clearance of triglyceride-rich lipoprotein from blood.

Predicted to be involved in several processes, including establishment of skin barrier; protein localization to tricellular tight junction; and tricellular tight junction assembly. Predicted to act upstream of or within maintenance of blood-brain barrier. Located in plasma membrane and tight junction.

Source: NCBI Gene 51599 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intrahepatic cholestasis (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 244 total — 2 likely-pathogenic
• MANE Select transcript: NM_205834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29572
Approved symbol	LSR
Name	lipolysis stimulated lipoprotein receptor
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	LISCH7, ILDR3
Ensembl gene	ENSG00000105699
Ensembl biotype	protein_coding
OMIM	616582
Entrez	51599

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 32 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000347609, ENST00000354900, ENST00000360798, ENST00000361790, ENST00000427250, ENST00000597446, ENST00000597933, ENST00000599658, ENST00000601623, ENST00000602003, ENST00000602044, ENST00000602122, ENST00000605618, ENST00000621372, ENST00000863865, ENST00000863866, ENST00000863867, ENST00000863868, ENST00000863869, ENST00000863870, ENST00000863871, ENST00000863872, ENST00000863873, ENST00000863874, ENST00000863875, ENST00000863876, ENST00000863877, ENST00000863878, ENST00000863879, ENST00000863880, ENST00000863881, ENST00000863882, ENST00000920054, ENST00000920055, ENST00000920056

RefSeq mRNA: 6 — MANE Select: NM_205834 NM_001260489, NM_001260490, NM_001385215, NM_015925, NM_205834, NM_205835

CCDS: CCDS12449, CCDS12450, CCDS12451, CCDS59376, CCDS92587

Canonical transcript exons

ENST00000605618 — 10 exons

Exon	Start	End
ENSE00000700288	35266836	35266967
ENSE00000700289	35266359	35266532
ENSE00000700290	35262546	35262692
ENSE00000862773	35267109	35267734
ENSE00000953266	35266679	35266738
ENSE00003528449	35258945	35259064
ENSE00003569570	35261925	35261981
ENSE00003638426	35249002	35249131
ENSE00003702119	35267824	35267964
ENSE00003715981	35250315	35250659

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 98.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.1020 / max 825.7705, expressed in 1064 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175257	58.7091	1030
175254	5.9853	855
175256	2.7769	767
175253	0.8070	503
175259	0.6673	299
175251	0.3639	203
175255	0.3302	238
175252	0.2608	167
175258	0.2014	124

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.25	gold quality
right lobe of liver	UBERON:0001114	96.98	gold quality
body of pancreas	UBERON:0001150	96.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.15	gold quality
minor salivary gland	UBERON:0001830	95.14	gold quality
lower esophagus mucosa	UBERON:0035834	94.77	gold quality
gall bladder	UBERON:0002110	94.42	gold quality
right uterine tube	UBERON:0001302	94.40	gold quality
liver	UBERON:0002107	94.24	gold quality
colonic mucosa	UBERON:0000317	94.18	gold quality
esophagus mucosa	UBERON:0002469	93.87	gold quality
pancreas	UBERON:0001264	93.70	gold quality
mouth mucosa	UBERON:0003729	93.52	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.42	gold quality
skin of abdomen	UBERON:0001416	93.35	gold quality
rectum	UBERON:0001052	93.27	gold quality
transverse colon	UBERON:0001157	93.07	gold quality
body of stomach	UBERON:0001161	93.00	gold quality
skin of leg	UBERON:0001511	92.83	gold quality
saliva-secreting gland	UBERON:0001044	92.66	gold quality
right lobe of thyroid gland	UBERON:0001119	92.59	gold quality
left lobe of thyroid gland	UBERON:0001120	92.32	gold quality
duodenum	UBERON:0002114	92.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.14	gold quality
stomach	UBERON:0000945	91.73	gold quality
islet of Langerhans	UBERON:0000006	91.62	gold quality
thyroid gland	UBERON:0002046	91.44	gold quality
adenohypophysis	UBERON:0002196	91.41	gold quality
metanephros cortex	UBERON:0010533	91.41	gold quality
jejunal mucosa	UBERON:0000399	91.16	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	115.43
E-MTAB-8410	yes	45.07
E-GEOD-135922	yes	12.99
E-MTAB-7249	yes	11.09
E-GEOD-110499	no	80.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting LSR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-1914-3P	95.07	63.37	762
HSA-MIR-1277-3P	93.47	68.97	156

Literature-anchored findings (GeneRIF, showing 22)

• LISCH7 may have a role in progression of human colon cancer (PMID:17975147)
• LSR defines tricellular contacts in epithelial cellular sheets by acting as a landmark to recruit tricellulin for tricellular tight junction formation. (PMID:21245199)
• findings show that Clostridium spiroforme toxin (CST)enters target cells via the lipolysis-stimulated lipoprotein receptor; findings indicate that CST shares LSR with C. difficile CDT and C. perfringens iota toxin as a host cell surface receptor (PMID:22252869)
• These data show that Clostridium difficile binary toxin CDT induces clustering of the lipolysis-stimulated lipoprotein receptor into lipid rafts. (PMID:23631918)
• analysis of how Clostridium difficile binary toxin CDT interacts with its host cell receptor, Lipolysis-stimulated Lipoprotein Receptor (PMID:25882847)
• Results of this study provide novel evidence that tricellular tight junctions protein LSR negatively regulates cancer cell progression and development in endometrial cancer. (PMID:27036040)
• Lipolysis-stimulated lipoprotein receptor (LSR)-deficient CaCo-2 cells exhibited increased cell proliferation. (PMID:27391068)
• this study shows that loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in endometrial cancer (PMID:28071680)
• Lipolysis-stimulated lipoprotein receptors (LSRs) localized to bicellular junctions in association with myosin regulatory light chain 2 (MRLC2) at low cell densities and to tricellular contacts when myosin phosphatase target subunit 1 (MYPT1) localized to the bicellular regions. (PMID:28493278)
• These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia and its involvement in cardiovascular disease pathology. (PMID:29178324)
• Study found a significant epistatic interaction between APOE and two lipolysis-stimulated lipoprotein receptor (LSR) variants, rs34259399 and rs916147. Interestingly, the interaction of LSR polymorphisms with APOE non-epsilon4 alleles increased Alzheimer Disease risk. (PMID:29858039)
• In the salivary gland ducts from patients with IgG4-related disease there was significant infiltration of IgG-positive plasma cells, and expression of GBP-1, CLDN-7 and LSR was increased. (PMID:30044945)
• In pancreatic cancer, LSR contributes to the epithelial barrier and malignancy via growth factors and may be a potential targeting molecule in the therapy. (PMID:31650247)
• Localization of Tricellular Tight Junction Molecule LSR at Midbody and Centrosome During Cytokinesis in Human Epithelial Cells. (PMID:31662022)
• Potentiation of cancerous progression by LISCH7 via direct stimulation of TGFB1 transcription in triple-negative breast cancer. (PMID:32048750)
• ASPP2 suppression promotes malignancy via LSR and YAP in human endometrial cancer. (PMID:32266459)
• HMGB1-downregulated angulin-1/LSR induces epithelial barrier disruption via claudin-2 and cellular metabolism via AMPK in airway epithelial Calu-3 cells. (PMID:32423802)
• Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3. (PMID:33105684)
• LSR promotes epithelial ovarian cancer cell survival under energy stress through the LKB1-AMPK pathway. (PMID:33388415)
• LSR Promotes Cell Proliferation and Invasion in Lung Cancer. (PMID:33763152)
• Translocation of LSR from tricellular corners causes macropinocytosis at cell-cell interface as a trigger for breaking out of contact inhibition. (PMID:34403506)
• Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-beta-dependent cell metabolism in human lung adenocarcinoma A549 cells. (PMID:36961882)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lsr	ENSDARG00000099291
mus_musculus	Lsr	ENSMUSG00000001247
rattus_norvegicus	Lsr	ENSRNOG00000021053

Paralogs (2): ILDR2 (ENSG00000143195), ILDR1 (ENSG00000145103)

Protein

Protein identifiers

Lipolysis-stimulated lipoprotein receptor — Q86X29 (reviewed: Q86X29)

Alternative names: Angulin-1

All UniProt accessions (8): Q86X29, A0A8Z5AA41, A0A8Z5ABK9, A0A8Z5DL71, M0QZL9, M0R0W1, M0R1W9, S4R3V8

UniProt curated annotations — full annotation on UniProt →

Function. Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells. Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions.

Subunit / interactions. Homotrimer or homotetramer. Assembles into cell-cell contacts. Interacts (via the cytoplasmic domain) with MARVELD2 (via C-terminal cytoplasmic domain); the interaction is required to recruit MARVELD2 to tricellular contacts. Interacts with OCLN.

Subcellular location. Cell membrane. Cell junction. Tight junction.

Post-translational modifications. Phosphorylation at Ser-365 by MAPK8/JNK1 and MAPK9/JNK2 may be required for exclusive localization at tricellular tight junstions. Polyubiquitinated at Lys-638 via ‘Lys-63’-linked ubiquitin chains; deubiquitinated by USP53.

Disease relevance. Defects in LSR may be the cause of familial intrahepatic cholestasis.

Similarity. Belongs to the immunoglobulin superfamily. LISCH7 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q86X29-1	1	yes
Q86X29-2	2
Q86X29-3	3
Q86X29-4	4
Q86X29-5	5
Q86X29-6	6

RefSeq proteins (6): NP_001247418, NP_001247419, NP_001372144, NP_057009, NP_991403, NP_991404 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008664	LISCH7	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051874	Ig-like_domain-LISCH7	Family

Pfam: PF05624

UniProt features (47 total): modified residue 19, splice variant 7, compositionally biased region 5, sequence conflict 5, topological domain 2, sequence variant 2, region of interest 2, chain 1, transmembrane region 1, disulfide bond 1, cross-link 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86X29-F1	57.52	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (20): 336, 365, 371, 389, 432, 436, 453, 464, 467, 493, 501, 528, 530, 535, 540, 579, 631, 643, 646, 638

Disulfide bonds (1): 111–218

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8964038	LDL clearance
R-HSA-8964046	VLDL clearance
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8964043	Plasma lipoprotein clearance

MSigDB gene sets: 232 (showing top): RNGTGGGC_UNKNOWN, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, AREB6_03, GOBP_CELL_JUNCTION_ORGANIZATION, JAZAG_TGFB1_SIGNALING_DN, UEDA_PERIFERAL_CLOCK, MARTINEZ_RB1_TARGETS_DN, IRF1_Q6, HEN1_01, HSIAO_LIVER_SPECIFIC_GENES, GOBP_EPIDERMIS_DEVELOPMENT, BOYAULT_LIVER_CANCER_SUBCLASS_G6_DN

GO Biological Process (8): liver development (GO:0001889), epithelial structure maintenance (GO:0010669), maintenance of blood-brain barrier (GO:0035633), establishment of blood-brain barrier (GO:0060856), establishment of skin barrier (GO:0061436), protein localization to tricellular tight junction (GO:0061833), tricellular tight junction assembly (GO:1904274), regulation of lipid metabolic process (GO:0019216)

GO Molecular Function (0):

GO Cellular Component (12): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cell junction (GO:0030054), very-low-density lipoprotein particle (GO:0034361), low-density lipoprotein particle (GO:0034362), chylomicron (GO:0042627), tricellular tight junction (GO:0061689), extracellular exosome (GO:0070062), tight junction (GO:0070160), endomembrane system (GO:0012505), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Plasma lipoprotein clearance	2
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
tissue homeostasis	2
tight junction	2
plasma lipoprotein particle	2
gland development	1
hepaticobiliary system development	1
central nervous system development	1
cell development	1
skin epidermis development	1
protein localization to cell-cell junction	1
tight junction assembly	1
lipid metabolic process	1
regulation of primary metabolic process	1
membrane	1
cell periphery	1
apical junction complex	1
triglyceride-rich plasma lipoprotein particle	1
extracellular vesicle	1
cell-cell junction	1
vacuole	1
plasma membrane	1
cell junction	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSR	MARVELD2	Q8N4S9	948
LSR	APOE	P02649	516
LSR	APOB	P04114	511
LSR	J3KSM2	J3KSM2	503
LSR	CD44	P16070	494
LSR	LTF	P02788	468
LSR	ILDR2	Q71H61	463
LSR	CLDN12	P56749	420
LSR	TMEM181	Q9P2C4	401
LSR	OCLN	Q16625	394
LSR	CLDN1	O95832	374
LSR	LRP1	Q07954	373
LSR	PCNT	O95613	362
LSR	IGSF5	Q9NSI5	356
LSR	CSTB	P04080	353
LSR	DEFA4	P12838	353

IntAct

170 interactions, top by confidence:

A	B	Type	Score
LSR	YWHAG	psi-mi:“MI:0915”(physical association)	0.830
LSR	YWHAB	psi-mi:“MI:0915”(physical association)	0.810
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
LSMEM2	STX7	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAE	SRSF10	psi-mi:“MI:0914”(association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ADAM33	LRP5	psi-mi:“MI:0914”(association)	0.530
IL9R	RETSAT	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
PCDHB7	C2CD2L	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
HFE	ADAM10	psi-mi:“MI:0914”(association)	0.530
KCNK16	B3GAT3	psi-mi:“MI:0914”(association)	0.530

BioGRID (258): LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS), LSR (Affinity Capture-MS)

ESM2 similar proteins: A2XMN1, A2XX39, A4GRC6, A8INQ0, A8JID5, B9G4M9, O49067, P06487, P07562, P09715, P12640, P13291, P16046, P16753, P17471, P17473, P28925, P28936, P29326, P33426, P36342, P84454, Q00958, Q01JD1, Q03500, Q04611, Q08354, Q08355, Q0JAI1, Q2QPW2, Q40505, Q5BIR3, Q5W6B9, Q66630, Q6S6U0, Q6SW62, Q6UDF4, Q6UDL6, Q705F3, Q71FD5

Diamond homologs: B5TVM2, Q32NM7, Q5R8C7, Q71H61, Q86SU0, Q86X29, Q8CBR1, Q99KG5, Q9WU74

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PTK2B	“up-regulates activity”	LSR	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	42.0×	4e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	37.0×	6e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	37.0×	6e-08
GRB2 events in EGFR signaling	5	30.0×	3e-05
SHC1 events in EGFR signaling	5	28.1×	3e-05
Activation of BH3-only proteins	7	27.4×	4e-07
GRB2 events in ERBB2 signaling	5	25.0×	5e-05
SHC1 events in ERBB2 signaling	5	18.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
acetylcholine receptor signaling pathway	5	20.7×	2e-03
membrane depolarization	5	16.9×	3e-03
protein targeting	5	12.1×	9e-03
monoatomic ion transmembrane transport	7	9.6×	3e-03
cell surface receptor protein tyrosine kinase signaling pathway	7	8.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

244 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	157
Likely benign	46
Benign	19

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4277337	NM_205834.4(LSR):c.353G>C (p.Cys118Ser)	Likely pathogenic
4531715	NM_205834.4(LSR):c.779-2A>G	Likely pathogenic

SpliceAI

1558 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35250656:GGAA:G	donor_gain	1.0000
19:35250657:G:T	donor_gain	1.0000
19:35250657:GAA:G	donor_gain	1.0000
19:35250657:GAAG:G	donor_gain	1.0000
19:35250660:G:GG	donor_gain	1.0000
19:35266357:A:AG	acceptor_gain	1.0000
19:35266358:G:GG	acceptor_gain	1.0000
19:35266358:GT:G	acceptor_gain	1.0000
19:35266531:AGGT:A	donor_loss	1.0000
19:35266532:GGTG:G	donor_loss	1.0000
19:35266533:GTGA:G	donor_loss	1.0000
19:35266534:T:A	donor_loss	1.0000
19:35266831:CCTA:C	acceptor_loss	1.0000
19:35266833:TA:T	acceptor_loss	1.0000
19:35266834:A:AG	acceptor_gain	1.0000
19:35266834:A:G	acceptor_loss	1.0000
19:35266835:G:GG	acceptor_gain	1.0000
19:35266835:G:T	acceptor_loss	1.0000
19:35266835:GA:G	acceptor_gain	1.0000
19:35266835:GAA:G	acceptor_gain	1.0000
19:35266963:GCGGG:G	donor_gain	1.0000
19:35266964:CGGGG:C	donor_loss	1.0000
19:35266965:GGG:G	donor_gain	1.0000
19:35266966:GG:G	donor_gain	1.0000
19:35266966:GGG:G	donor_gain	1.0000
19:35266966:GGGTA:G	donor_loss	1.0000
19:35266967:GG:G	donor_gain	1.0000
19:35266967:GGTAA:G	donor_loss	1.0000
19:35266968:G:GG	donor_gain	1.0000
19:35266968:GTA:G	donor_loss	1.0000

AlphaMissense

3881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35259000:C:G	C218W	1.000
19:35250437:T:A	W126R	0.999
19:35250437:T:C	W126R	0.999
19:35250439:G:C	W126C	0.999
19:35250439:G:T	W126C	0.999
19:35250448:G:C	K129N	0.999
19:35250448:G:T	K129N	0.999
19:35250455:T:A	C132S	0.999
19:35250455:T:C	C132R	0.999
19:35250456:G:A	C132Y	0.999
19:35250456:G:C	C132S	0.999
19:35250457:C:G	C132W	0.999
19:35250590:G:C	A177P	0.999
19:35250591:C:A	A177D	0.999
19:35258954:T:C	L203P	0.999
19:35258976:G:C	W210C	0.999
19:35258976:G:T	W210C	0.999
19:35258998:T:A	C218S	0.999
19:35258998:T:C	C218R	0.999
19:35258999:G:A	C218Y	0.999
19:35258999:G:C	C218S	0.999
19:35259053:T:C	L236P	0.999
19:35266905:A:T	E409V	0.999
19:35250392:T:A	C111S	0.998
19:35250392:T:C	C111R	0.998
19:35250393:G:A	C111Y	0.998
19:35250393:G:C	C111S	0.998
19:35250394:T:G	C111W	0.998
19:35250432:T:A	V124D	0.998
19:35250443:T:G	Y128D	0.998

dbSNP variants (sampled 300 via entrez): RS1000259836 (19:35248429 C>A,T), RS1000386752 (19:35251828 C>T), RS1000549916 (19:35258639 G>A), RS1000617993 (19:35257504 C>A,T), RS1000871716 (19:35247082 A>C,G), RS1000925413 (19:35252447 C>A,G), RS1000959976 (19:35247799 T>C,G), RS1000977165 (19:35252129 C>T), RS1001005535 (19:35258460 A>C,T), RS1001124859 (19:35258162 T>C,G), RS1001614158 (19:35262013 C>G,T), RS1001624856 (19:35250730 C>T), RS1001781309 (19:35256809 T>C), RS1001819832 (19:35266598 G>A), RS1001928996 (19:35251398 T>C)

Disease associations

OMIM: gene MIM:616582 | disease phenotypes: MIM:211600

GenCC curated gene-disease

Disease	Classification	Inheritance
intrahepatic cholestasis	Moderate	Autosomal recessive

Mondo (3): progressive familial intrahepatic cholestasis type 1 (MONDO:0008892), progressive familial intrahepatic cholestasis (MONDO:0015762), intrahepatic cholestasis (MONDO:0019072)

Orphanet (2): Progressive familial intrahepatic cholestasis type 1 (Orphanet:79306), Progressive familial intrahepatic cholestasis (Orphanet:172)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004601_191	Red blood cell count	5.000000e-11
GCST90006995_7	Gut microbiota relative abundance (unclassified genus belonging to family Lachnospiraceae)	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002780	Cholestasis, Intrahepatic	C06.130.120.135.250; C06.552.150

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
sodium arsenite	increases expression, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Arsenic Trioxide	decreases expression, decreases response to substance	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
daidzein	affects cotreatment, affects expression	1
bisphenol A	decreases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
daidzin	affects cotreatment, affects expression	1
cobaltous chloride	increases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, increases expression	1
nickel sulfate	increases expression	1
genistin	affects cotreatment, affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
glycitein	affects cotreatment, affects expression	1
corosolic acid	increases expression	1
monomethylarsonous acid	increases expression	1
glycitin	affects cotreatment, affects expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8PH	Ubigene HCT 116 LSR KO	Cancer cell line	Male

Clinical trials (associated diseases)

29 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01576458	PHASE3	COMPLETED	Ursodeoxycholic Acid in the Treatment of Intrahepatic Cholestasis of Pregnancy
NCT03353454	PHASE3	WITHDRAWN	A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT03566238	PHASE3	COMPLETED	This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
NCT03659916	PHASE3	COMPLETED	Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC
NCT03905330	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
NCT04185363	PHASE3	COMPLETED	An Extension Study of Maralixibat in Patients With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT05543187	PHASE3	COMPLETED	A Study of TAK-625 for the Treatment of Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT02057718	PHASE2	COMPLETED	Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis
NCT04729751	PHASE2	COMPLETED	A Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS).
NCT02963077	PHASE1	COMPLETED	A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384
NCT03082937	PHASE1	COMPLETED	An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects
NCT01381939	Not specified	COMPLETED	Induction of Labor in Intrahepatic Cholestasis of Pregnancy
NCT06781242	Not specified	RECRUITING	Genotype-phenotype Relationship Between Cryptogenic Cholestasis and Familial Intrahepatic Cholestasis
NCT01784718	Not specified	NO_LONGER_AVAILABLE	Buphenyl Therapy for Byler’s Disease
NCT01949766	Not specified	NO_LONGER_AVAILABLE	Transition From Buphenyl to RAVICTI for the Therapy of Byler Disease
NCT02094222	Not specified	NO_LONGER_AVAILABLE	Expanded Access Protocol for an Intermediate Size Population - RAVICTI for Byler Disease
NCT02131623	Not specified	COMPLETED	Validation of the Itch Reported Outcome (ItchRO) Diaries in Pediatric Cholestatic Liver Disease
NCT03930810	Not specified	ENROLLING_BY_INVITATION	NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion
NCT04071197	Not specified	UNKNOWN	Gastrostomy-Biliary Diversion: Innovative Management for Bile Canalicular Transport Disorders
NCT04483531	Not specified	APPROVED_FOR_MARKETING	Odevixibat for the Treatment of Progressive Familial Intrahepatic Cholestasis
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05704517	Not specified	UNKNOWN	Progressive Familial Intrahepatic Cholestasis in Indian Children - Establishing an Indian PFIC Registry
NCT06193928	Not specified	RECRUITING	Long-Term SafEty and Clinical Outcomes of LivmArli in Patients in the United States (LEAP-US)
NCT06777914	Not specified	RECRUITING	Familial Intrahepatic Cholestasis-related Genes Associated with Disease Susceptibility in Hepato-biliary Cancers
NCT06778174	Not specified	RECRUITING	Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)
NCT07185919	Not specified	RECRUITING	A Study of the Effectiveness, Safety and the Long-term Outcomes of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Who Take Odevixibat (Bylvay) in South Korea
NCT07293897	Not specified	RECRUITING	A Database Study of Maralixibat (TAK-625) in Participants With Alagille Syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT07317193	Not specified	RECRUITING	DEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE
NCT07588880	Not specified	RECRUITING	A Study of the Effectiveness, Safety and the Long-term Outcomes of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Who Take Odevixibat (Bylvay) in China