Rotor syndrome

Summary

Rotor syndrome (MONDO:0009379) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 274
• Phenotypes (HPO): 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0000952	Jaundice	Very frequent (80-99%)
HP:0002908	Conjugated hyperbilirubinemia	Very frequent (80-99%)
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0002904	Hyperbilirubinemia	Frequent (30-79%)
HP:0010473	Porphyrinuria	Frequent (30-79%)
HP:0031811	Bilirubinuria	Frequent (30-79%)
HP:0001046	Intermittent jaundice	Occasional (5-29%)
HP:0032106	Conjunctival icterus	Occasional (5-29%)
HP:0000989	Pruritus	Excluded (0%)
HP:0031137	Storage in hepatocytes	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Rotor syndrome
Mondo ID	MONDO:0009379
OMIM	237450
Orphanet	3111
ICD-11	1965776012
SNOMED CT	32891000
UMLS	C0220991
MedGen	67435
GARD	0000218
MedDRA	10039234
Is cancer (heuristic)	no

Also known as: HBLRR · hyperbilirubinemia, ROTOR type · hyperbilirubinemia, Rotor type · hyperbilirubinemia, rotor type, digenic · Rotor syndrome · Rotor-type hyperbilirubinemia

Data availability: 274 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of porphyrin metabolism › inborn disorder of bilirubin metabolism › hereditary hyperbilirubinemia › Rotor syndrome

Related subtypes (6): Gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, hyperbilirubinemia, conjugated, type 3, hyperbilirubinemia, shunt, primary, transient familial neonatal hyperbilirubinemia

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

274 retrieved; paginated sample, class counts are floors:

163 uncertain significance, 40 benign, 24 likely benign, 16 conflicting classifications of pathogenicity, 12 benign/likely benign, 9 pathogenic, 9 likely pathogenic, 1 drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
4820241	Single allele	LOC126861478	Pathogenic	criteria provided, single submitter
30437	NM_006446.5(SLCO1B1):c.1738C>T (p.Arg580Ter)	SLCO1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
30439	NM_006446.5(SLCO1B1):c.757C>T (p.Arg253Ter)	SLCO1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
915961	GRCh37/hg19 12p12.2-12.1(chr12:21017576-21404166)	SLCO1B1	Pathogenic	no assertion criteria provided
1330928	NM_019844.4(SLCO1B3):c.1637dup (p.Leu546fs)	SLCO1B3	Pathogenic	criteria provided, single submitter
30487	SLCO1B3, 7.2-KB DEL	SLCO1B3	Pathogenic	no assertion criteria provided
30488	NM_019844.4(SLCO1B3):c.1747+1G>A	SLCO1B3	Pathogenic	criteria provided, multiple submitters, no conflicts
632183	NM_019844.4(SLCO1B3):c.971-2A>G	SLCO1B3	Pathogenic	criteria provided, single submitter
977762	NC_000012.11:g.21014093_21014094insLINE1	SLCO1B3	Pathogenic	criteria provided, single submitter
2506538	GRCh37/hg19 12p12.2-12.1(chr12:21007963-21392123)	SLCO1B1	Likely pathogenic	criteria provided, single submitter
2572603	NM_006446.5(SLCO1B1):c.1865+1G>A	SLCO1B1	Likely pathogenic	criteria provided, single submitter
3780636	NM_006446.5(SLCO1B1):c.1497+2T>A	SLCO1B1	Likely pathogenic	criteria provided, single submitter
3780639	NM_006446.5(SLCO1B1):c.226+1G>A	SLCO1B1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3892500	NM_006446.5(SLCO1B1):c.1634T>G (p.Leu545Ter)	SLCO1B1	Likely pathogenic	criteria provided, single submitter
4685640	NM_006446.5(SLCO1B1):c.1009_1010dup (p.Tyr338fs)	SLCO1B1	Likely pathogenic	criteria provided, single submitter
1330934	NM_019844.4(SLCO1B3):c.1135+1G>A	SLCO1B3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3374929	NM_019844.4(SLCO1B3):c.481+1G>C	SLCO1B3	Likely pathogenic	criteria provided, single submitter
3766697	NM_019844.4(SLCO1B3):c.727+1_727+2delinsA	SLCO1B3	Likely pathogenic	criteria provided, single submitter
37346	NM_006446.5(SLCO1B1):c.521T>C (p.Val174Ala)	SLCO1B1	drug response	reviewed by expert panel
307950	NM_006446.5(SLCO1B1):c.1331+9A>G	SLCO1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
307951	NM_006446.5(SLCO1B1):c.1332-14T>C	SLCO1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
811089	NM_006446.5(SLCO1B1):c.664A>G (p.Ile222Val)	SLCO1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
883990	NM_006446.5(SLCO1B1):c.1498-15T>C	SLCO1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2436101	NM_019844.4(SLCO1B3):c.67C>T (p.Arg23Cys)	SLCO1B3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
307886	NM_019844.4(SLCO1B3):c.335C>A (p.Ser112Tyr)	SLCO1B3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
307890	NM_019844.4(SLCO1B3):c.542G>A (p.Arg181His)	SLCO1B3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
307902	NM_019844.4(SLCO1B3):c.1272A>G (p.Leu424=)	SLCO1B3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
307907	NM_019844.4(SLCO1B3):c.1593A>G (p.Thr531=)	SLCO1B3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
618375	NM_019844.4(SLCO1B3):c.484T>G (p.Cys162Gly)	SLCO1B3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
712105	NM_019844.4(SLCO1B3):c.205_209dup (p.Asp70fs)	SLCO1B3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · 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
SLCO1B1	Supportive	Autosomal recessive	Rotor syndrome
SLCO1B3	Supportive	Autosomal recessive	Rotor syndrome

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLCO1B1	Orphanet:3111	Rotor syndrome
SLCO1B3	Orphanet:3111	Rotor syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLCO1B1	HGNC:10959	ENSG00000134538	Q9Y6L6	Solute carrier organic anion transporter family member 1B1	gencc,clinvar
SLCO1B3	HGNC:10961	ENSG00000111700	Q9NPD5	Solute carrier organic anion transporter family member 1B3	gencc,clinvar
SLCO1B3-SLCO1B7	HGNC:54403	ENSG00000257046	F5H094	SLCO1B3-SLCO1B7 readthrough transcript protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLCO1B1	Solute carrier organic anion transporter family member 1B1	Mediates the Na(+)-independent uptake of organic anions.
SLCO1B3	Solute carrier organic anion transporter family member 1B3	Mediates the Na(+)-independent uptake of organic anions.
SLCO1B3-SLCO1B7	SLCO1B3-SLCO1B7 readthrough transcript protein	Mediates the Na(+)-independent uptake of organic anions.

Protein-family classification

Druggable: 3 · 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	3	77.8×	2e-06

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLCO1B1	Transporter	yes		Kazal_dom, OATP, MFS_dom
SLCO1B3	Transporter	yes		Kazal_dom, OATP, MFS_dom
SLCO1B3-SLCO1B7	Transporter	yes		Kazal_dom, OATP, MFS_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	1
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	3
right lobe of liver	3
male germ line stem cell (sensu Vertebrata) in testis	2
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLCO1B1	29	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
SLCO1B3	106	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
SLCO1B3-SLCO1B7	19		yes	primordial germ cell in gonad, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLCO1B1	1,380
SLCO1B3	996
SLCO1B3-SLCO1B7	0

Intra-cohort edges

A	B	Sources
SLCO1B1	SLCO1B3	biogrid_interaction, intact

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLCO1B1	Q9Y6L6	9
SLCO1B3	Q9NPD5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLCO1B3-SLCO1B7	F5H094	81.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Metabolism of porphyrins	2	1427.5×	4e-06	SLCO1B1, SLCO1B3
Atorvastatin ADME	2	1427.5×	4e-06	SLCO1B1, SLCO1B3
Organic anion transport by SLCO transporters	2	1038.2×	5e-06	SLCO1B1, SLCO1B3
Heme degradation	2	815.7×	6e-06	SLCO1B1, SLCO1B3
Recycling of bile acids and salts	2	601.0×	9e-06	SLCO1B1, SLCO1B3
Bile acid and bile salt metabolism	2	496.5×	1e-05	SLCO1B1, SLCO1B3
Transport of vitamins, nucleosides, and related molecules	2	271.9×	3e-05	SLCO1B1, SLCO1B3
Drug ADME	2	228.4×	4e-05	SLCO1B1, SLCO1B3
SLC transporter disorders	2	203.9×	5e-05	SLCO1B1, SLCO1B3
Disorders of transmembrane transporters	2	139.3×	9e-05	SLCO1B1, SLCO1B3
Metabolism of steroids	2	137.6×	9e-05	SLCO1B1, SLCO1B3
Defective SLCO1B3 causes hyperbilirubinemia, Rotor type (HBLRR)	1	5710.0×	2e-04	SLCO1B3
Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR)	1	5710.0×	2e-04	SLCO1B1
SLC-mediated transmembrane transport	2	59.2×	4e-04	SLCO1B1, SLCO1B3
Metabolism of lipids	2	31.6×	0.001	SLCO1B1, SLCO1B3
Transport of small molecules	2	25.1×	0.002	SLCO1B1, SLCO1B3
Disease	2	13.1×	0.006	SLCO1B1, SLCO1B3
Metabolism	2	11.6×	0.007	SLCO1B1, SLCO1B3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sodium-independent organic anion transport	3	1123.5×	3e-09	SLCO1B1, SLCO1B3, SLCO1B3-SLCO1B7
bile acid and bile salt transport	3	648.1×	1e-08	SLCO1B1, SLCO1B3, SLCO1B3-SLCO1B7
heme catabolic process	2	1021.3×	2e-06	SLCO1B1, SLCO1B3
obsolete organic anion transport	2	535.0×	7e-06	SLCO1B1, SLCO1B3
monoatomic ion transport	2	104.0×	1e-04	SLCO1B1, SLCO1B3
xenobiotic metabolic process	2	99.4×	1e-04	SLCO1B1, SLCO1B3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
SLCO1B1	CANDESARTAN CILEXETIL
SLCO1B3	CANDESARTAN CILEXETIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLCO1B1	57	4
SLCO1B3	50	4
SLCO1B3-SLCO1B7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANDESARTAN CILEXETIL	4	SLCO1B1, SLCO1B3
TELMISARTAN	4	SLCO1B1, SLCO1B3
SIMVASTATIN	4	SLCO1B1
TELITHROMYCIN	4	SLCO1B1, SLCO1B3
PRAVASTATIN	4	SLCO1B1, SLCO1B3
MOMETASONE FUROATE	4	SLCO1B1, SLCO1B3
ATAZANAVIR	4	SLCO1B1, SLCO1B3
HYDROXYZINE PAMOATE	4	SLCO1B1, SLCO1B3
ERYTHROMYCIN ETHYLSUCCINATE	4	SLCO1B1, SLCO1B3
OLMESARTAN MEDOXOMIL	4	SLCO1B1, SLCO1B3
DICLOXACILLIN SODIUM	4	SLCO1B1, SLCO1B3
BETA CAROTENE	4	SLCO1B1, SLCO1B3
NONOXYNOL 9	4	SLCO1B1, SLCO1B3
ATORVASTATIN	4	SLCO1B1
VINBLASTINE	4	SLCO1B1, SLCO1B3
CYCLOSPORINE	4	SLCO1B1, SLCO1B3
RITONAVIR	4	SLCO1B1, SLCO1B3
CARBENOXOLONE SODIUM	4	SLCO1B1, SLCO1B3
CLARITHROMYCIN	4	SLCO1B1, SLCO1B3
DIGOXIN	4	SLCO1B1, SLCO1B3
LOSARTAN	4	SLCO1B1, SLCO1B3
ERYTHROMYCIN ESTOLATE	4	SLCO1B1, SLCO1B3
TACROLIMUS ANHYDROUS	4	SLCO1B1
RIFAMPIN	4	SLCO1B1, SLCO1B3
ATORVASTATIN CALCIUM	4	SLCO1B1, SLCO1B3
SIROLIMUS	4	SLCO1B1
SULFASALAZINE	4	SLCO1B1, SLCO1B3
PACLITAXEL	4	SLCO1B1, SLCO1B3
RIFAMYCIN	4	SLCO1B1, SLCO1B3
GEMFIBROZIL	4	SLCO1B1, SLCO1B3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLCO1B1	242	Functional:106, ADMET:82, Binding:53, Toxicity:1
SLCO1B3	136	ADMET:79, Binding:30, Functional:27

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SLCO1B1	242
SLCO1B3	136

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
SLCO1B1	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)
CANDESARTAN CILEXETIL	4	SLCO1B1, SLCO1B3
TELMISARTAN	4	SLCO1B1, SLCO1B3
SIMVASTATIN	4	SLCO1B1
TELITHROMYCIN	4	SLCO1B1, SLCO1B3
PRAVASTATIN	4	SLCO1B1, SLCO1B3
MOMETASONE FUROATE	4	SLCO1B1, SLCO1B3
ATAZANAVIR	4	SLCO1B1, SLCO1B3
HYDROXYZINE PAMOATE	4	SLCO1B1, SLCO1B3
ERYTHROMYCIN ETHYLSUCCINATE	4	SLCO1B1, SLCO1B3
OLMESARTAN MEDOXOMIL	4	SLCO1B1, SLCO1B3
DICLOXACILLIN SODIUM	4	SLCO1B1, SLCO1B3
BETA CAROTENE	4	SLCO1B1, SLCO1B3
NONOXYNOL 9	4	SLCO1B1, SLCO1B3
ATORVASTATIN	4	SLCO1B1
VINBLASTINE	4	SLCO1B1, SLCO1B3
CYCLOSPORINE	4	SLCO1B1, SLCO1B3
RITONAVIR	4	SLCO1B1, SLCO1B3
CARBENOXOLONE SODIUM	4	SLCO1B1, SLCO1B3
CLARITHROMYCIN	4	SLCO1B1, SLCO1B3
DIGOXIN	4	SLCO1B1, SLCO1B3
LOSARTAN	4	SLCO1B1, SLCO1B3
ERYTHROMYCIN ESTOLATE	4	SLCO1B1, SLCO1B3
TACROLIMUS ANHYDROUS	4	SLCO1B1
RIFAMPIN	4	SLCO1B1, SLCO1B3
ATORVASTATIN CALCIUM	4	SLCO1B1, SLCO1B3
SIROLIMUS	4	SLCO1B1
SULFASALAZINE	4	SLCO1B1, SLCO1B3
PACLITAXEL	4	SLCO1B1, SLCO1B3
RIFAMYCIN	4	SLCO1B1, SLCO1B3
GEMFIBROZIL	4	SLCO1B1, SLCO1B3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SLCO1B1, SLCO1B3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SLCO1B3-SLCO1B7
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLCO1B3-SLCO1B7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.