SCARB2

Summary

SCARB2 (scavenger receptor class B member 2, HGNC:1665) is a protein-coding gene on chromosome 4q21.1, encoding Lysosome membrane protein 2 (Q14108). Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting.

The protein encoded by this gene is a type III glycoprotein that is located primarily in limiting membranes of lysosomes and endosomes. Earlier studies in mice and rat suggested that this protein may participate in membrane transportation and the reorganization of endosomal/lysosomal compartment. The protein deficiency in mice was reported to impair cell membrane transport processes and cause pelvic junction obstruction, deafness, and peripheral neuropathy. Further studies in human showed that this protein is a ubiquitously expressed protein and that it is involved in the pathogenesis of HFMD (hand, foot, and mouth disease) caused by enterovirus-71 and possibly by coxsackievirus A16. Mutations in this gene caused an autosomal recessive progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 950 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive myoclonus epilepsy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 563 total — 21 pathogenic, 15 likely-pathogenic (top 6% of genes corpus-wide)
• GTEx eGene: eQTL in 35 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 82
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.68 (unconstrained)
• MANE Select transcript: NM_005506
• Interaction hub: 4,860 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1665
Approved symbol	SCARB2
Name	scavenger receptor class B member 2
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	HLGP85, LIMPII, SR-BII, LIMP-2
Ensembl gene	ENSG00000138760
Ensembl biotype	protein_coding
OMIM	602257
Entrez	950

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 16 protein_coding, 11 retained_intron, 9 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000264896

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 7, TSL 4: 2, TSL 5: 16

ENST00000264896, ENST00000452464, ENST00000502908, ENST00000509994, ENST00000511129, ENST00000638175, ENST00000638295, ENST00000638372, ENST00000638409, ENST00000638567, ENST00000638603, ENST00000638663, ENST00000638680, ENST00000638843, ENST00000639145, ENST00000639300, ENST00000639324, ENST00000639715, ENST00000639738, ENST00000640076, ENST00000640341, ENST00000640634, ENST00000640640, ENST00000640880, ENST00000640900, ENST00000640916, ENST00000640957, ENST00000682785, ENST00000862442, ENST00000862443, ENST00000862444, ENST00000862445, ENST00000921155, ENST00001004723, ENST00001012270, ENST00001012272, ENST00001106266, ENST00001139015

RefSeq mRNA: 2 — MANE Select: NM_005506 NM_001204255, NM_005506

CCDS: CCDS3577, CCDS56335

Canonical transcript exons

ENST00000264896 — 12 exons

Exon	Start	End
ENSE00000725188	76179517	76179705
ENSE00000725195	76180954	76181101
ENSE00000725202	76195707	76195864
ENSE00000800847	76174144	76174313
ENSE00000800848	76169867	76169985
ENSE00000800849	76168403	76168476
ENSE00000800850	76166250	76166301
ENSE00000800851	76163225	76163383
ENSE00001077893	76176437	76176528
ENSE00001077894	76175791	76175910
ENSE00001278458	76158737	76161751
ENSE00003803172	76213427	76213824

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 96.4160 / max 554.2903, expressed in 1818 samples.

Highest expression (Bgee): inferior vagus X ganglion, subthalamic nucleus, germinal epithelium of ovary, superior vestibular nucleus, lateral globus pallidus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SCARB2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 35 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	5.0e-45	-0.79	4:76233712:C:T
Skin Not Sun Exposed Suprapubic	sqtl	7.3e-45	-0.84	4:76234438:C:T
Cells Cultured fibroblasts	eqtl	4.4e-27	+0.37	4:76175453:G:T
Skin Sun Exposed Lower leg	eqtl	2.0e-23	+0.23	4:76234438:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.6e-22	+0.25	4:76234438:C:T
Brain Spinal cord cervical c-1	eqtl	9.8e-22	+0.35	4:76200193:A:G
Artery Aorta	eqtl	4.5e-19	+0.33	4:76193998:G:A
Esophagus Mucosa	sqtl	1.6e-17	+1.16	4:76227060:C:A
Minor Salivary Gland	sqtl	2.2e-14	+1.49	4:76233986:T:C
Testis	eqtl	1.3e-10	+0.14	4:76297904:G:T
Heart Atrial Appendage	eqtl	1.4e-10	-0.22	4:76189879:C:T
Whole Blood	eqtl	8.2e-09	+0.18	4:76210141:G:A
Nerve Tibial	sqtl	2.5e-08	+0.47	4:76179915:T:C
Cells EBV-transformed lymphocytes	eqtl	1.4e-07	+0.97	4:76213864:T:G
Heart Left Ventricle	eqtl	2.2e-07	-0.16	4:76206873:A:G
Esophagus Mucosa	eqtl	3.6e-07	+0.18	4:76149137:G:A
Pancreas	eqtl	1.1e-06	-0.32	4:76251292:C:T
Colon Transverse	eqtl	2.4e-06	-0.31	4:76240146:C:T
Brain Nucleus accumbens basal ganglia	eqtl	4.3e-06	+0.15	4:76178508:A:C
Brain Putamen basal ganglia	eqtl	5.2e-06	+0.15	4:76149137:G:A

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
52653	44.6128	1813
52648	23.1673	1749
52655	17.7450	1757
52647	5.7308	1465
52649	1.8545	1074
52654	1.3197	867
52650	0.8589	329
52651	0.6372	246
52657	0.4401	221
203248	0.0497	21

Top tissues by expression

showing 100 of 302 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.61	gold quality
subthalamic nucleus	UBERON:0001906	99.53	gold quality
germinal epithelium of ovary	UBERON:0001304	99.42	gold quality
superior vestibular nucleus	UBERON:0007227	99.42	gold quality
lateral globus pallidus	UBERON:0002476	99.41	gold quality
pons	UBERON:0000988	99.37	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.37	gold quality
substantia nigra pars compacta	UBERON:0001965	99.30	gold quality
mammary duct	UBERON:0001765	99.28	gold quality
trigeminal ganglion	UBERON:0001675	99.27	gold quality
middle temporal gyrus	UBERON:0002771	99.26	gold quality
corpus callosum	UBERON:0002336	99.25	gold quality
endothelial cell	CL:0000115	99.23	gold quality
stromal cell of endometrium	CL:0002255	99.06	gold quality
cardia of stomach	UBERON:0001162	99.03	gold quality
urethra	UBERON:0000057	99.00	gold quality
ventral tegmental area	UBERON:0002691	98.99	gold quality
lower lobe of lung	UBERON:0008949	98.97	gold quality
pylorus	UBERON:0001166	98.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.83	gold quality
corpus epididymis	UBERON:0004359	98.83	gold quality
pericardium	UBERON:0002407	98.78	gold quality
islet of Langerhans	UBERON:0000006	98.74	gold quality
renal medulla	UBERON:0000362	98.74	gold quality
cortical plate	UBERON:0005343	98.69	gold quality
visceral pleura	UBERON:0002401	98.66	gold quality
parotid gland	UBERON:0001831	98.61	gold quality
synovial joint	UBERON:0002217	98.56	gold quality
skin of hip	UBERON:0001554	98.53	gold quality
parietal lobe	UBERON:0001872	98.43	gold quality
saphenous vein	UBERON:0007318	98.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.40	gold quality
pigmented layer of retina	UBERON:0001782	98.39	gold quality
retina	UBERON:0000966	98.37	gold quality
seminal vesicle	UBERON:0000998	98.36	gold quality
ganglionic eminence	UBERON:0004023	98.33	gold quality
dorsal root ganglion	UBERON:0000044	98.32	gold quality
colonic epithelium	UBERON:0000397	98.31	gold quality
postcentral gyrus	UBERON:0002581	98.30	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.30	gold quality
upper leg skin	UBERON:0004262	98.26	gold quality
endometrium	UBERON:0001295	98.25	gold quality
superficial temporal artery	UBERON:0001614	98.25	gold quality
colonic mucosa	UBERON:0000317	98.19	gold quality
caput epididymis	UBERON:0004358	98.08	gold quality
parietal pleura	UBERON:0002400	98.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.07	gold quality
entorhinal cortex	UBERON:0002728	98.04	gold quality
globus pallidus	UBERON:0001875	98.00	gold quality
gall bladder	UBERON:0002110	97.98	gold quality
vena cava	UBERON:0004087	97.87	gold quality
epithelium of mammary gland	UBERON:0003244	97.84	gold quality
rectum	UBERON:0001052	97.83	gold quality
mammary gland	UBERON:0001911	97.83	gold quality
thoracic mammary gland	UBERON:0005200	97.82	gold quality
epithelium of nasopharynx	UBERON:0001951	97.81	gold quality
cauda epididymis	UBERON:0004360	97.81	gold quality
nasopharynx	UBERON:0001728	97.79	gold quality
spinal cord	UBERON:0002240	97.79	gold quality
penis	UBERON:0000989	97.72	gold quality
pleura	UBERON:0000977	97.67	gold quality
mammalian vulva	UBERON:0000997	97.66	gold quality
medial globus pallidus	UBERON:0002477	97.62	gold quality
jejunum	UBERON:0002115	97.60	gold quality
ventricular zone	UBERON:0003053	97.58	gold quality
nipple	UBERON:0002030	97.52	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.50	gold quality
adult organism	UBERON:0007023	97.50	gold quality
pharyngeal mucosa	UBERON:0000355	97.42	gold quality
gingival epithelium	UBERON:0001949	97.42	gold quality
body of tongue	UBERON:0011876	97.42	gold quality
right lung	UBERON:0002167	97.37	gold quality
upper lobe of lung	UBERON:0008948	97.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.36	gold quality
superior frontal gyrus	UBERON:0002661	97.36	gold quality
adrenal tissue	UBERON:0018303	97.35	gold quality
calcaneal tendon	UBERON:0003701	97.34	gold quality
jejunal mucosa	UBERON:0000399	97.30	gold quality
upper lobe of left lung	UBERON:0008952	97.25	gold quality
tibia	UBERON:0000979	97.22	gold quality
gingiva	UBERON:0001828	97.22	gold quality
biceps brachii	UBERON:0001507	97.16	gold quality
right coronary artery	UBERON:0001625	97.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.11	gold quality
descending thoracic aorta	UBERON:0002345	97.03	gold quality
bronchial epithelial cell	CL:0002328	97.02	gold quality
endocervix	UBERON:0000458	96.98	gold quality
pancreas	UBERON:0001264	96.94	gold quality
superior surface of tongue	UBERON:0007371	96.87	gold quality
gastrocnemius	UBERON:0001388	96.84	gold quality
body of pancreas	UBERON:0001150	96.83	gold quality
saliva-secreting gland	UBERON:0001044	96.78	gold quality
ovary	UBERON:0000992	96.75	gold quality
coronary artery	UBERON:0001621	96.75	gold quality
muscle of leg	UBERON:0001383	96.74	gold quality
occipital lobe	UBERON:0002021	96.73	gold quality
primary visual cortex	UBERON:0002436	96.70	gold quality
oral cavity	UBERON:0000167	96.69	gold quality
thoracic aorta	UBERON:0001515	96.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	13.28
E-CURD-112	no	3.15
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	373.1
Medulla oblongata	tissue	293.0
Substantia nigra	tissue	279.0
Midbrain	tissue	273.4
Thalamus	tissue	262.5
Corpus callosum	tissue	261.2
Pons	tissue	258.0
Superior colliculi	tissue	240.5
Hypothalamus	tissue	230.2
Periaqueductal gray	tissue	228.4
Cerebral cortex	tissue	207.0	high
Somatosensory cortex	tissue	207.0
Occipital cortex	tissue	201.1
Motor cortex	tissue	195.0
Hippocampal formation	tissue	191.2
Prefrontal cortex	tissue	186.1
Septum	tissue	186.1
Temporal cortex	tissue	182.6
Entorhinal cortex	tissue	182.0
Putamen	tissue	176.1
Ventral forebrain	tissue	176.0
Amygdala	tissue	171.7
Retrosplenial and cingulate cortex	tissue	171.6
Retrosplenial cortex	tissue	169.9
Insular cortex	tissue	166.8
Basal ganglia	tissue	135.8	high
Olfactory bulb	tissue	127.6
Locus coeruleus	tissue	101.0
Nucleus accumbens	tissue	91.1
Cerebellum	tissue	84.8	high
Hippocampus	tissue	75.5	high
Caudate putamen	tissue	74.3
Salivary gland	tissue	72.1	high
Liver	tissue	67.1	high
Prostate	tissue	65.4	high
Choroid plexus	tissue	64.8
Frontal cortex	tissue	64.2
Postcentral gyrus	tissue	64.0
Lung	tissue	63.4	high
Placenta	tissue	62.0	high
Tongue	tissue	59.9
Ovary	tissue	56.1	medium
Pancreas	tissue	55.3	high
Epididymis	tissue	55.2	high
Colon	tissue	53.3	high
Thyroid gland	tissue	53.3	high
Urinary bladder	tissue	52.8	high
Stomach 1	tissue	51.7	high
Gallbladder	tissue	51.2	high
Breast	tissue	51.0	not detected
Adipose tissue	tissue	50.8	medium
Heart muscle	tissue	50.1	high
Seminal vesicle	tissue	49.7	high
Parathyroid gland	tissue	48.9
Cervix	tissue	46.4	low
Skeletal muscle	tissue	45.7	low
Rectum	tissue	44.6	high
Retina	tissue	44.3
Spleen	tissue	42.8	high
Small intestine	tissue	42.0	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (373.1), Dorsal spinal cord (317.2), White matter (261.2), Lateral funiculus (white matter) (212.4), Parieto-temporal junction (white matter) (208.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARD, SPI1, STAT2

miRNA regulators (miRDB)

Targeting SCARB2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 109 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4307	99.82	70.45	3374

Functional genomics

gnomAD constraint: pLI 0.00286, LOEUF 0.683, missense Z 1.64 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000264896 — one region, missense o/e 0.84. ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Functional analysis of the mouse homolog (PMID:12620969)
• Several putative signalling motifs identified in the C-terminus of human SR-BII, which are absent from SR-BI, interact with signalling molecules to mobilize stored cholesteryl esters and/or promote the efflux of intracellular free cholesterol. (PMID:14570588)
• High density lipoprotein endocytosis by scavenger receptor SR-BII is clathrin-dependent and requires a carboxyl-terminal dileucine motif. (PMID:16368683)
• Residues favoring AP3 binding introduced into a protein that is transported via the PM such as the invariant chain can re-route such protein into direct sorting to late endosomal/lysosomal structures. (PMID:16542748)
• Scavenger receptors SR-BI and SR-BII localized mainly to the ganglion cell layer and photoreceptor outer segments; in the latter they appear to be associated with microtubules. (PMID:17110915)
• HCV soluble E2 can interact with human SR-BI and SR-BII (PMID:17215280)
• Regulation of alternative splicing of liver scavenger receptor class B gene by estrogen. (PMID:17673517)
• SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies. (PMID:18308289)
• Scavenger receptor B2 is a cellular receptor for enterovirus 71. (PMID:19543282)
• Study of SCARB2 mutations finds unsolved cases of progressive myoclonus epilepsy without renal impairment, especially those resembling Unverricht-Lundborg disease. (PMID:19847901)
• Action Myoclonus-Renal Failure Syndrome-causing mutations within LIMP-2 affect the binding to beta-glucocerebrosidase. (PMID:19933215)
• smooth muscle cells and macrophages expressing scavenger receptor BI/II in different stages of atherosclerosis (PMID:20032583)
• L929 cells expressing chimeras that carried amino acids 142 to 204 from the human sequence were susceptible to enterovirus 71, while chimeras that carried the mouse sequence in this region were not. (PMID:21389126)
• Two sisters are described with action myoclonus-renal failure (AMRF) syndrome resulting from a mutation in the SCARB2 gene. (PMID:21782476)
• Sequencing of SCARB2 genomic and cDNA identified a heterozygous, maternally inherited novel mutation (SCARB2 ) (PMID:21796727)
• We showed that just four genes, G3BP2, SCARB2, CSNK1A1 and SPRR2B, can classify patients as presence of lymph node metastasis negative or positive, with 80.0% accuracy. (PMID:21985131)
• in rare cases heterozygous SCARB2 mutations may be associated with demyelinating polyneuropathy features. (PMID:22032306)
• This study demonistrated that patients with SCARB2 mutations showed the clinical and neurophysiologic phenotype of progressive myoclonus epilepsy , extending the spectrum reported in the typical action myoclonus renal failure syndrome. (PMID:22050460)
• The residues between 144 and 151 are critical for SCARB2 binding to VP1 of EV71 and seven residues from the human receptor could convert murine SCARB2, an otherwise inefficient receptor, to an efficient receptor for EV71 viral infection. (PMID:22219187)
• This study supported a genetic contribution of the SCARB2 locus to PD; future studies in larger cohorts are necessary to verify this finding. (PMID:22223122)
• Results show that EV71 binds to SCARB2 and triggers a clathrin- and dynamin-dependent endocytosis for its entry. (PMID:22272359)
• Coxsackievirus A infection is via celluar virus receptor SCARB2. (PMID:22438546)
• Our data do not support the association of SNP rs6812193 with PD in Han Chinese of mainland China. (PMID:22465138)
• H171 residue in LIMP-2 is necessary for LIMP-2 and beta-glucocerebrosidase binding (PMID:22537104)
• Lysosomal storage disorders are associated with deficiencies of alternative lysosomal receptors LIMPII and sortilin and/or of their cargos. (Review) (PMID:22884962)
• These results indicated that SCARB2 is capable of viral binding, viral internalization, and viral uncoating and that the low infection efficiency of L-PSGL1 cells is due to the inability of PSGL1 to induce viral uncoating. (PMID:23302872)
• study of two Japanese siblings with late-onset progressive myoclonus epilepsy without renal failure having a novel homozygous SCARB2 mutation (PMID:23325613)
• identified no novel exonic variants in SCARB2 but confirmed the association between SNP rs6812193 and Parkinson’s disease. (PMID:23408458)
• Human SCARB2-transgenic mice are a useful model for assessing anti-EV71 medications. (PMID:23451246)
• SCARB2 is implicated in the lysosomal pathway recently associated with Parkinson disease (PD) pathogenesis. The rs6812193 polymorphism doesn’t increase susceptibility to PD in the Greek population. (PMID:23473716)
• Results suggest that this hSCARB2 transgenic mouse could represent a useful animal model for the study of enterovirus 71 (EV71) infection. (PMID:23959904)
• Mutations in LIMP-2, the specific receptor for glucocerebrosidase that is missing in Gaucher disease patients, substantially contribute to the pathology and heterogeneity of the disease. (Review) (PMID:24389070)
• A novel SCARB2 mutation was indicated by reduced Beta-glucocerebrosidase activity in progressive myoclonus epilepsy. (PMID:24485911)
• a novel mutation in SCARB2 as a cause of progressive myoclonus epilepsy in China (PMID:24620919)
• SNCA and SCARB2 loci are also associated with dementia with Lewy bodies, after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in Parkinson’s. (PMID:24973356)
• Data indicate that scavenger receptor SCARB2 triggers uncoating of human enterovirus 71 (EV71) under low pH conditions. (PMID:24986489)
• SCARB2 and PSGL-1 in human gastrointestinal tract, lung, and brain tissues correlated with the distribution of pathological changes seen in EV71 infection. (PMID:24997419)
• The LIMP-2/SCARB2 binding sequences for enterovirus 71 and GCase are not similar, indicating that LIMP-2/SCARB2 may have multiple or overlapping binding sites with differing specificities. (PMID:25202012)
• In LIMP-2-deficient brains a significant reduction in GC activity led to lipid storage, disturbed autophagic/lysosomal function, and alpha-synuclein accumulation. (PMID:25316793)
• Disease-causing cathepsin-F mutants fail to cleave LIMP-2. Our findings provide evidence that LIMP-2 represents an in vivo substrate of cathepsin-F with relevance for understanding the pathophysiology of type-B-Kufs-disease. (PMID:25576872)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	scarb2c	ENSDARG00000089844
mus_musculus	Scarb2	ENSMUSG00000029426
rattus_norvegicus	Scarb2	ENSRNOG00000002225
drosophila_melanogaster	ninaD	FBGN0002939
drosophila_melanogaster	crq	FBGN0015924
drosophila_melanogaster	santa-maria	FBGN0025697
drosophila_melanogaster	pes	FBGN0031969
drosophila_melanogaster	CG7227	FBGN0031970
drosophila_melanogaster	CG31741	FBGN0051741
caenorhabditis_elegans		WBGENE00013039
caenorhabditis_elegans		WBGENE00013578
caenorhabditis_elegans		WBGENE00015389

Paralogs (2): SCARB1 (ENSG00000073060), CD36 (ENSG00000135218)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1196458) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 64 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal stria vascularis morphology	2
premature death	2
cochlear ganglion degeneration	2
abnormal nervous system morphology	2
stria vascularis degeneration	2
abnormal strial marginal cell morphology	2
abnormal auditory brainstem response	2
increased leukocyte cell number	1
increased neutrophil cell number	1
decreased monocyte cell number	1
hydronephrosis	1
abnormal ureter morphology	1
enlarged lymph nodes	1
tremors	1
paralysis	1
demyelination	1
abnormal phrenic nerve morphology	1
abnormal Schwann cell morphology	1
decreased body weight	1
distended abdomen	1
polydipsia	1
limb grasping	1
polyuria	1
deafness	1
neurodegeneration	1

+39 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mesocricetus auratus	P70110	92.4%	Diamond
Cricetulus griseus	Q60417	89.0%	Diamond
Bos taurus	O18824	88.4%	Diamond
Sus scrofa	Q8SQC1	88.4%	Diamond
Dictyostelium discoideum	Q55FQ9	49.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FAM47E-STBD1	protein-coding	100631383
NUP54-DT	ncRNA	124900718
CCDC158	protein-coding	339965
NUP54	protein-coding	53371
STBD1	protein-coding	8987
FAM47E	protein-coding	100129583
ART3	protein-coding	419
CXCL11	protein-coding	6373
SDAD1-AS1	ncRNA	101928809
CXCL10	protein-coding	3627
CXCL9	protein-coding	4283
SDAD1	protein-coding	55153

Protein

Protein identifiers

Lysosome membrane protein 2 — Q14108 (reviewed: Q14108)

Alternative names: 85 kDa lysosomal membrane sialoglycoprotein, CD36 antigen-like 2, Lysosome membrane protein II, Scavenger receptor class B member 2

All UniProt accessions (14): A0A1W2PNX7, A0A1W2PPU6, A0A1W2PPX5, A0A1W2PPX6, A0A1W2PQB7, A0A1W2PQL5, A0A1W2PQR6, A0A1W2PRF6, A0A1W2PRS1, A0A1W2PS43, A0A1W2PS70, A0A1W2PSE4, D6RDG0, Q14108

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting. (Microbial infection) Acts as a receptor for enterovirus 71.

Subunit / interactions. Interacts with GBA1. (Microbial infection) Interacts with enterovirus 71 capsid proteins VP1 and VP2.

Subcellular location. Lysosome membrane.

Disease relevance. Epilepsy, progressive myoclonic 4, with or without renal failure (EPM4) [MIM:254900] A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM4 is an autosomal recessive form associated with renal failure in some cases. Cognitive function is preserved. The disease is caused by variants affecting the gene represented in this entry. Genetic variants in SCARB2 can act as modifier of the phenotypic expression and severity of Gaucher disease.

Similarity. Belongs to the CD36 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14108-1	1	yes
Q14108-2	2

RefSeq proteins (2): NP_001191184, NP_005497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002159	CD36_fam	Family
IPR005429	LimpII	Family

Pfam: PF01130

UniProt features (76 total): strand 21, helix 18, glycosylation site 10, mutagenesis site 7, turn 7, topological domain 3, disulfide bond 2, transmembrane region 2, sequence variant 2, chain 1, splice variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
4Q4F	Crystal structure of LIMP-2 (space group C2)	X-RAY DIFFRACTION	2.8
4Q4B	Crystal structure of LIMP-2 (space group C2221)	X-RAY DIFFRACTION	2.82
4TW2	Crystal Structure of SCARB2 in Neural Condition (pH7.5)	X-RAY DIFFRACTION	2.89
4F7B	Structure of the lysosomal domain of limp-2	X-RAY DIFFRACTION	3
5UPH	Lipids bound lysosomal integral membrane protein 2	X-RAY DIFFRACTION	3
4TVZ	Crystal Structure of SCARB2 in Neural Condition (pH7.5)	X-RAY DIFFRACTION	3.01
6I2K	Structure of EV71 complexed with its receptor SCARB2	ELECTRON MICROSCOPY	3.4
5XBM	Structure of SCARB2-JL2 complex	X-RAY DIFFRACTION	3.5
4TW0	Crystal Structure of SCARB2 in Acidic Condition (pH4.8)	X-RAY DIFFRACTION	3.65
9FJF	Lysosomal transporting complex of beta-glucocerebrosidase (GCase) and lysosomal integral …	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14108-F1	93.01	0.82

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 5XBM, 9FJF

Human Protein Atlas

Protein class: Transporters, Predicted membrane proteins, Disease related genes, Potential drug targets, Human disease related genes, Epilepsy

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH supported · IF approved

Functional residue map

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

Disulfide bonds (2)

Type	Positions
Disulfide bond	274–329, 312–318

Glycosylation sites (10)

Type	Positions
N-linked (glcnac…) asparagine	206, 224, 249, 304, 325, 412, 430, 45, 68, 105

Mutagenesis-validated functional residues (7)

Position	Phenotype
475	prevents the targeting of the protein to lysosomes.
475	some loss in the efficiency of targeting of the protein to lysosomes.
476	does not prevent the targeting of the protein to lysosomes completely.
476	prevents the targeting of the protein to lysosomes.
476	normal targeting of the protein to lysosomes.
477	normal targeting of the protein to lysosomes.
478	normal targeting of the protein to lysosomes.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-199991	Membrane Trafficking	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 512 (showing top): GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_LYSOSOMAL_TRANSPORT, GCM_PTPRD, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GCM_ZNF198, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_PROTEIN_TARGETING, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME

GO Biological Process (12): protein targeting to lysosome (GO:0006622), receptor-mediated endocytosis (GO:0006898), autophagy (GO:0006914), positive regulation of neuron projection development (GO:0010976), aminophospholipid transport (GO:0015917), regulation of carbohydrate catabolic process (GO:0043470), regulation of endosome organization (GO:1904978), regulation of lysosome organization (GO:1905671), regulation of glucosylceramide catabolic process (GO:2000752), vesicle-mediated transport (GO:0016192), glycolipid catabolic process (GO:0019377), symbiont entry into host cell (GO:0046718)

GO Molecular Function (11): virus receptor activity (GO:0001618), phosphatidylserine binding (GO:0001786), transmembrane signaling receptor activity (GO:0004888), scavenger receptor activity (GO:0005044), cholesterol binding (GO:0015485), enzyme binding (GO:0019899), phosphatidylcholine binding (GO:0031210), cargo receptor activity (GO:0038024), protein homodimerization activity (GO:0042803), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (13): Golgi membrane (GO:0000139), lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), focal adhesion (GO:0005925), endosome membrane (GO:0010008), membrane (GO:0016020), endocytic vesicle membrane (GO:0030666), clathrin-coated endocytic vesicle membrane (GO:0030669), late endosome membrane (GO:0031902), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), lysosome (GO:0005764)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1

GO top-level categories

showing 60 of 68 GO namespaces:

Category	Terms
bounding membrane of organelle	3
vesicle-mediated transport	2
phospholipid binding	2
protein binding	2
lysosome	2
cytoplasmic vesicle membrane	2
protein targeting to vacuole	1
lysosomal transport	1
protein localization to lysosome	1
endocytosis	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
phospholipid transport	1
nitrogen compound transport	1
regulation of carbohydrate metabolic process	1
regulation of catabolic process	1
carbohydrate catabolic process	1
endosome organization	1
regulation of organelle organization	1
lysosome organization	1
regulation of vacuole organization	1
glucosylceramide catabolic process	1
regulation of lipid catabolic process	1
transport	1
cellular process	1
glycolipid metabolic process	1
lipid catabolic process	1
carbohydrate derivative catabolic process	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
anion binding	1
modified amino acid binding	1
signaling receptor activity	1
cargo receptor activity	1
sterol binding	1
alcohol binding	1
cation binding	1
quaternary ammonium group binding	1
molecular_function	1
molecular adaptor activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
Golgi apparatus	1
lytic vacuole membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cell-substrate junction	1
endosome	1
cellular anatomical structure	1
endocytic vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 36 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
protein targeting to lysosome	BP	mutant phenotype
regulation of carbohydrate catabolic process	BP	mutant phenotype
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
lysosomal membrane	CC	high-throughput assay
membrane	CC	high-throughput assay
cargo receptor activity	MF	mutant phenotype
enzyme binding	MF	physical interaction
protein homodimerization activity	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 4,860 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCARB2	PPARA	Q07869	856
SCARB2	PPARG	P37231	852
SCARB2	LDLR	P01130	829
SCARB2	LPL	P06858	806
SCARB2	DGAT1	O75907	804
SCARB2	ABCA1	O95477	803
SCARB2	TLR2	O60603	794
SCARB2	GYPA	P02724	778
SCARB2	THBS1	P07996	767
SCARB2	ADIPOQ	Q15848	751
SCARB2	PPARD	Q03181	748
SCARB2	SREBF1	P36956	741
SCARB2	FABP4	P15090	740
SCARB2	SCARF1	Q14162	731
SCARB2	CLEC7A	Q9BXN2	731

IntAct

Human interaction partners of SCARB2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
RHCG	physical association	0.590	2
CLDN19	physical association	0.560	3
ERGIC3	physical association	0.560	3
GPR37L1	physical association	0.560	3
GPX8	physical association	0.560	3
HIBADH	physical association	0.560	3
LAPTM4B	physical association	0.560	3
CLGN	association	0.530	1
CYP26B1	association	0.350	1
EIF2AK2	association	0.350	1
PLEKHG3	association	0.350	1
SGCE	association	0.350	1
SPAG9	association	0.350	1

BioGRID (225 interactions; top human partners by supporting records): GBA (Affinity Capture-MS; 3 records), PTPRK (Affinity Capture-MS; 3 records), NONO (Affinity Capture-MS; 2 records), PRPF8 (Affinity Capture-MS; 2 records), RAB27B (Affinity Capture-MS; 2 records), RHCG (Affinity Capture-MS; 2 records), SPAG9 (Affinity Capture-MS; 2 records), TPST1 (Affinity Capture-Western; 2 records), TPST2 (Affinity Capture-Western; 2 records), VAMP3 (Affinity Capture-MS; 2 records), ABCD3 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTL6A (Affinity Capture-MS), ACTR1A (Affinity Capture-MS), ACTR2 (Affinity Capture-MS)

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
GBA1-GRN-HSPA1A-SCARB2 complex	4	GBA1, GRN, HSPA1A, SCARB2
★ GBA1-IGF2R-SCARB2 complex	3	GBA1, IGF2R, SCARB2
★ IGF2R-SCARB2 complex	2	SCARB2, IGF2R
GBA1-SCARB2 complex	2	SCARB2, GBA1

Disease & clinical

Genetic variants

Variant evidence for SCARB2: 563 ClinVar records (36 pathogenic / likely pathogenic); 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	15
Uncertain significance	227
Likely benign	194
Benign	52

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 36 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
7377	NM_005506.4(SCARB2):c.434_435dup (p.Trp146fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
7378	NM_005506.4(SCARB2):c.862C>T (p.Gln288Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
268146	NM_005506.4(SCARB2):c.1270C>T (p.Arg424Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
268139	NM_005506.4(SCARB2):c.704+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	3
971806	NM_005506.4(SCARB2):c.956del (p.Leu319fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
268138	NM_005506.4(SCARB2):c.666_670del (p.Tyr222_Asn224delinsTer)	Pathogenic	criteria provided, single submitter	2
268142	NM_005506.4(SCARB2):c.1016dup (p.His341fs)	Pathogenic	criteria provided, single submitter	2
807488	NM_005506.4(SCARB2):c.134del (p.Asn45fs)	Pathogenic	criteria provided, single submitter	2
206723	NM_005506.4(SCARB2):c.1337del (p.Gly446fs)	Pathogenic	criteria provided, single submitter	1
1441270	NM_005506.4(SCARB2):c.850del (p.Tyr284fs)	Pathogenic	criteria provided, single submitter	1
1457513	NM_005506.4(SCARB2):c.638_639del (p.Tyr213fs)	Pathogenic	criteria provided, single submitter	1
2005737	NM_005506.4(SCARB2):c.1260_1261dup (p.Thr421fs)	Pathogenic	criteria provided, single submitter	1
2781498	NM_005506.4(SCARB2):c.226del (p.Leu76fs)	Pathogenic	criteria provided, single submitter	1
2846431	NM_005506.4(SCARB2):c.1030C>T (p.Gln344Ter)	Pathogenic	criteria provided, single submitter	1
4292546	NM_005506.4(SCARB2):c.994+1G>T	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore SCARB2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 859):

Position(s)	Effect	Δscore	Sites
4:76161752	acceptor_gain	1.0000
4:76161752–76161753	acceptor_loss	1.0000	4
4:76161761	acceptor_gain	1.0000
4:76169862	donor_loss	1.0000
4:76169865–76169866	donor_loss	1.0000	5
4:76180952–76180953	donor_loss	1.0000	5
4:76181102	acceptor_gain	1.0000
4:76181102–76181103	acceptor_loss	1.0000	5
4:76195705–76195706	donor_loss	1.0000	3
4:76195865–76195866	acceptor_loss	1.0000	5

AlphaMissense

901 missense substitutions predicted likely pathogenic (of 3,168 scored), across 277 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N206	8	0.885	0.957
D182	8	0.870	0.946
H341	8	0.846	0.940
F199	8	0.843	0.976
F168	8	0.830	0.954
H363	8	0.765	0.948
D131	8	0.763	0.827
C329	7	0.985	0.994
C312	7	0.983	0.991
C274	7	0.978	0.989
F311	7	0.974	0.994
F269	7	0.970	0.991
C318	7	0.966	0.984
F342	7	0.965	0.977
W231	7	0.963	0.985
W178	7	0.960	0.989
F67	7	0.953	0.966
W53	7	0.951	0.994
W240	7	0.946	0.992
Q384	7	0.926	0.985

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.86e-07
Lung Adenocarcinoma (validation)	unfavorable	0.000624
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000825

Disease associations

OMIM: gene MIM:602257 | disease phenotypes: MIM:254900, MIM:254800

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
action myoclonus-renal failure syndrome	Definitive	Autosomal recessive	4
progressive myoclonus epilepsy	Strong	Autosomal recessive
Unverricht-Lundborg syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
progressive myoclonus epilepsy	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Early onset or syndromic epilepsy	green
Hereditary neuropathy or pain disorder	green
Paediatric disorders	green
Proteinuric renal disease	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Unexplained kidney failure in young people	green
Unexplained young onset end-stage renal disease	green
Hereditary neuropathy	amber

Mondo (3): action myoclonus-renal failure syndrome (MONDO:0009699), progressive myoclonus epilepsy (MONDO:0020074), Unverricht-Lundborg syndrome (MONDO:0009698)

Orphanet (3): Action myoclonus-renal failure syndrome (Orphanet:163696), Progressive myoclonic epilepsy type 1 (Orphanet:308), Progressive myoclonic epilepsy (Orphanet:98261)

HPO phenotypes

showing 60 of 82 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000225	Gingival bleeding
HP:0000716	Depression
HP:0000726	Dementia
HP:0000790	Hematuria
HP:0000823	Delayed puberty
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000969	Edema
HP:0000978	Bruising susceptibility
HP:0000992	Cutaneous photosensitivity
HP:0001081	Cholelithiasis
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001300	Parkinsonism
HP:0001336	Myoclonus
HP:0001394	Cirrhosis
HP:0001399	Hepatic failure
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001510	Growth delay
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001876	Pancytopenia
HP:0001882	Decreased total leukocyte count
HP:0001892	Abnormal bleeding
HP:0001895	Normochromic anemia
HP:0001903	Anemia
HP:0001928	Abnormality of coagulation
HP:0001971	Hypersplenism
HP:0002015	Dysphagia
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002080	Intention tremor
HP:0002092	Pulmonary arterial hypertension
HP:0002174	Postural tremor
HP:0002176	Spinal cord compression
HP:0002197	Generalized-onset seizure
HP:0002202	Pleural effusion
HP:0002240	Hepatomegaly
HP:0002317	Unsteady gait
HP:0002345	Action tremor
HP:0002392	EEG with polyspike wave complexes
HP:0002653	Bone pain
HP:0002750	Delayed skeletal maturation
HP:0002756	Pathologic fracture
HP:0002758	Osteoarthritis
HP:0002797	Osteolysis
HP:0002953	Vertebral compression fracture

GWAS associations

10 associations:

Study	Trait	p-value
GCST007876_20	Estimated glomerular filtration rate	2e-72
GCST002544_18	Parkinson’s disease	3e-11
GCST001126_1	Parkinson’s disease	8e-10
GCST009325_26	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1e-9
GCST002783_484	Body mass index	5e-9
GCST002783_81	Body mass index	8e-9
GCST004495_10	BMI (adjusted for smoking behaviour)	2e-7
GCST007009_4	Hippocampal volume	3e-7
GCST002783_8	Body mass index	2e-6
GCST004497_14	Body mass index (joint analysis main effects and smoking interaction)	2e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0005035	hippocampal volume

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D020191	Myoclonic Epilepsies, Progressive	C10.228.140.490.375.130.650; C10.228.140.490.493.063.650
D020194	Unverricht-Lundborg Syndrome	C10.228.140.490.375.130.650.900; C10.228.140.490.493.063.650.900; C10.574.500.875; C16.320.400.940

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Valproic Acid	decreases methylation, increases expression	3
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	2
Cisplatin	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, affects reaction	1
CGP 52608	increases reaction, affects binding	1
U 0126	affects expression, affects reaction	1
corosolic acid	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1

Cellosaurus cell lines

8 cell lines: 6 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5HZ	293-SCARB2	Transformed cell line	Female
CVCL_A5IA	RD-SCARB2	Cancer cell line	Female
CVCL_A5IB	Vero-SCARB2	Spontaneously immortalized cell line	Female
CVCL_B9BE	Abcam MCF-7 SCARB2 KO	Cancer cell line	Female
CVCL_D1U9	Abcam U-87MG SCARB2 KO	Cancer cell line	Male
CVCL_D5FI	HeLa::TMEM192-3xHA SCARB2 partial KO	Cancer cell line	Female
CVCL_E0N7	Ubigene HeLa SCARB2 KO	Cancer cell line	Female
CVCL_E0ZN	Ubigene NCI-H1299 SCARB2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 95 trials:

NCT	Phase	Status	Title
NCT01129557	Phase 4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	Phase 4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	Phase 4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	Phase 4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	Phase 4	ACTIVE_NOT_RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT03490487	Phase 4	UNKNOWN	Electroclinical Effect of Steroid in Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
NCT04610879	Phase 4	TERMINATED	Changing Agendas on Sleep, Treatment and Learning in Epilepsy
NCT00357669	Phase 3	COMPLETED	Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease in Adolescents and Adults
NCT00368251	Phase 3	COMPLETED	Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults
NCT03351569	Phase 3	UNKNOWN	Intravenous Immunoglobulin for Unverricht-Lundborg Disease.
NCT01164098	Phase 3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	Phase 3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	Phase 3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	Phase 3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	Phase 3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	Phase 3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
NCT00639119	Phase 2	UNKNOWN	Effect of Ropinirole Hydrochloride in Progressive Myoclonic Epilepsy of Unverricht-Lundborg Type
NCT00550342	Phase 2	WITHDRAWN	Rituximab Treatment of Focal Segmental Glomerulosclerosis
NCT00814255	Phase 2	COMPLETED	Novel Therapies for Resistant FSGS (FONTII): Phase II Clinical Trial
NCT01613118	Phase 2	COMPLETED	Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis
NCT02592798	Phase 2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT03366337	Phase 2	COMPLETED	A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX
NCT03448692	Phase 2	TERMINATED	A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT03536754	Phase 2	COMPLETED	A Study of CCX140-B in Subjects With FSGS
NCT03598036	Phase 2	TERMINATED	Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis
NCT03649152	Phase 2	COMPLETED	Safety and Effectiveness of Propagermanium in Focal Segmental Glomerulosclerosis Participants Receiving Irbesartan
NCT03703908	Phase 2	TERMINATED	A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome
NCT04009668	Phase 2	COMPLETED	Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
NCT04573920	Phase 2	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With Proteinuric Glomerular Diseases
NCT05003986	Phase 2	RECRUITING	Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases
NCT05267262	Phase 2	COMPLETED	Study to Evaluate R3R01 in Patients With Alport Syndrome and Patients With Focal Segmental Glomerulosclerosis
NCT05441826	Phase 2	TERMINATED	Efficacy and Safety of VB119 in Subjects With Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS)
NCT06500702	Phase 2	RECRUITING	A Study to Evaluate the Efficacy and Safety of Frexalimab, Brivekimig, or Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis or Minimal Change Disease
NCT06664814	Phase 2	RECRUITING	An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Podocyte Diseases
NCT06983028	Phase 2	RECRUITING	Atacicept in Multiple Glomerular Diseases
NCT07268638	Phase 2	RECRUITING	A Study of Praliciguat in Participants With Focal Segmental Glomerulosclerosis (FSGS)
NCT07614477	Phase 2	RECRUITING	Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of EVER001 in Participants With Selected Proteinuric Glomerular Diseases
NCT00464321	Phase 1	COMPLETED	Safety Study of GC1008 in Patients With Focal Segmental Glomerulosclerosis (FSGS) of Single Doses of GC1008 in Patients With Treatment Resistant Idiopathic FSGS
NCT00782561	Phase 1	TERMINATED	Safety and Pharmacokinetics of FG-3019 in Adolescents and Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT00816478	Phase 1	TERMINATED	Effect of Oral Galactose on Focal Segmental Glomerulosclerosis (FSGS) Permeability Factor
NCT00816504	Phase 1	WITHDRAWN	Effect of Galactose on Permeblity Factor in Patients With FSGS and CKD Stage 5
NCT02382874	Phase 1	UNKNOWN	Allogenic AD-MSC Transplantation in Idiopathic Nephrotic Syndrome (Focal Segmental Glomerulosclerosis)
NCT02693366	Phase 1	COMPLETED	Stem Cell Therapy for Patients With Focal Segmental Glomerulosclerosis
NCT05942625	Phase 1	RECRUITING	A First in Human Study to Evaluate Safety, Tolerability, Pharmacology of HS-10390 in Healthy Subjects
NCT05955872	Phase 1	COMPLETED	A Study Evaluating the Relative Bioavailability and Food Effect of a Tablet Formulation of VX-147
NCT06529796	Phase 1	COMPLETED	Evaluation of the Pharmacokinetics and Safety of Inaxaplin in Participants With Mild or Moderate Hepatic Impairment
NCT07267026	Phase 1	RECRUITING	A Study to Evaluate the Safety, Tolerability and PK of SK-09
NCT06593951	Not specified	RECRUITING	Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
NCT06923241	Not specified	COMPLETED	Nutri-score Labelling in a UK Restaurant Setting: a Randomised Control Trial
NCT02896270	Phase 2/3	UNKNOWN	Valproic Acid for Idiopathic Nephrotic Syndrome
NCT07213960	Phase 2/3	RECRUITING	A Sequential Phase 2/3 Study of APL2 in Patients With Focal Segmental Glomerulosclerosis
NCT07499700	Phase 2/3	RECRUITING	A Clinical Study of BAT4406F Injection in Patients With Minimal Change Disease/Focal Segmental Glomerulosclerosis
NCT00007475	Phase 1/2	COMPLETED	Permeability Factor in Focal Segmental Glomerulosclerosis
NCT05508009	Phase 1/2	RECRUITING	Early Trial of Allogeneic Hematopoietic Stem Cell Transplantation for Patients Who Will Receive a Kidney Transplant From the Same Donor
NCT06090227	Phase 1/2	RECRUITING	AMPK-activation by Metformin in FSGS: AMP-FSGS
NCT03763643	Early Phase 1	COMPLETED	PRI-VENT FSGS: Preemptive Rituximab to Prevent Recurrent Focal Segmental Glomerulosclerosis Post-Transplant
NCT00001393	Not specified	COMPLETED	Genetic Markers for Focal Segmental Glomerulosclerosis
NCT00255398	Not specified	COMPLETED	Kidney Disease Biomarkers
NCT00801463	Not specified	COMPLETED	Prednisone Plus Tripterygium Wilfordii Treatment of Adult Patients With Idiopathic Focal Segmental Glomerulosclerosis
NCT00883636	Not specified	TERMINATED	Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis