SCARB2

scavenger receptor class B member 2, the group of Scavenger receptors

Basic information

Region (hg38): 4:76158737-76234536

Previous symbols: [ "CD36L2" ]

Links

ENSG00000138760 ∙ NCBI:950 ∙ OMIM:602257 ∙ HGNC:1665 ∙ Uniprot:Q14108 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• action myoclonus-renal failure syndrome (Strong), mode of inheritance: AR
• Unverricht-Lundborg syndrome (Supportive), mode of inheritance: AR
• action myoclonus-renal failure syndrome (Supportive), mode of inheritance: AR
• progressive myoclonus epilepsy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progressive myoclonic 4, with or without renal failure	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Renal	15364701; 17030781; 18424452; 18308289; 19847901; 21782476; 21670406; 22032306; 22050460; 22767442
In addition to other manifestations, renal dysfunction and cardiomyopathy have been reported; Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCARB2 gene.

• Progressive myoclonic epilepsy (14 variants)
• Action myoclonus-renal failure syndrome (8 variants)
• not provided (4 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCARB2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	93	1	95
missense			164	2	3	169
nonsense	4	2				6
start loss						0
frameshift	12	1	2			15
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	6	1			8
splice region			14	15		29
non coding			4	66	50	120
Total	17	9	174	161	54

Highest pathogenic variant AF is 0.000151

Variants in SCARB2

This is a list of pathogenic ClinVar variants found in the SCARB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-76161596-C-T			Benign (Jun 14, 2018)
4-76161646-G-C			Benign (Jun 14, 2018)
4-76161717-G-T		Progressive myoclonic epilepsy	Uncertain significance (Nov 27, 2021)
4-76161717-GT-G		Progressive myoclonic epilepsy	Uncertain significance (Mar 18, 2022)
4-76161720-C-T		Progressive myoclonic epilepsy	Uncertain significance (Aug 27, 2021)
4-76161725-G-A		Progressive myoclonic epilepsy	Likely benign (Apr 08, 2020)
4-76161734-T-G		Progressive myoclonic epilepsy • Action myoclonus-renal failure syndrome	Uncertain significance (Aug 23, 2022)
4-76161738-T-A		Progressive myoclonic epilepsy • Action myoclonus-renal failure syndrome	Uncertain significance (Sep 29, 2022)
4-76161738-T-C		Action myoclonus-renal failure syndrome	not provided (-)
4-76161743-C-T		Progressive myoclonic epilepsy • Inborn genetic diseases	Likely benign (Nov 27, 2023)
4-76161744-G-A		Inborn genetic diseases	Uncertain significance (Apr 15, 2024)
4-76161747-G-A		Progressive myoclonic epilepsy • Inborn genetic diseases	Uncertain significance (Aug 02, 2022)
4-76161759-A-G		Progressive myoclonic epilepsy	Likely benign (Jul 09, 2019)
4-76161761-A-C			Likely benign (Jun 20, 2018)
4-76161762-G-C		Progressive myoclonic epilepsy	Uncertain significance (Apr 21, 2021)
4-76161764-A-G		Progressive myoclonic epilepsy	Likely benign (Nov 07, 2022)
4-76161766-A-T		Progressive myoclonic epilepsy	Likely benign (Jun 30, 2023)
4-76161767-G-C		Progressive myoclonic epilepsy	Likely benign (Feb 26, 2023)
4-76161917-TCAG-T			Benign (Jun 18, 2018)
4-76161929-A-T			Benign (Jun 23, 2018)
4-76161957-T-C			Likely benign (Jun 22, 2018)
4-76161971-C-A			Benign (Jun 14, 2018)
4-76162031-G-A			Benign (Jun 19, 2018)
4-76163202-AAGTTCCTTCAGCC-A		not specified • Progressive myoclonic epilepsy	Likely benign (Dec 03, 2022)
4-76163210-T-TC		Progressive myoclonic epilepsy	Likely benign (Oct 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCARB2	protein_coding	protein_coding	ENST00000264896	12	55157

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000895	0.997	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	194	253	0.766	0.0000125	3158
Missense in Polyphen		50	76.298	0.65533		943
Synonymous	0.923	85	96.5	0.881	0.00000514	901
Loss of Function	2.61	11	25.1	0.438	0.00000124	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.00	0.00
South Asian	0.000164	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting. {ECO:0000269|PubMed:18022370}.
• Disease: DISEASE: Epilepsy, progressive myoclonic 4, with or without renal failure (EPM4) [MIM:254900]: An autosomal recessive progressive myoclonic epilepsy associated with renal failure in some cases. Cognitive function is preserved. Myoclonus is a brief, involuntary twitching of a muscle or a group of muscles. {ECO:0000269|PubMed:18308289, ECO:0000269|PubMed:18424452, ECO:0000269|PubMed:19454373, ECO:0000269|PubMed:21670406}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Genetic variants in SCARB2 can act as modifier of the phenotypic expression and severity of Gaucher disease. {ECO:0000269|PubMed:21796727}.
• Pathway: Lysosome - Homo sapiens (human);Primary Focal Segmental Glomerulosclerosis FSGS;Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis (Consensus)

Recessive Scores

• pRec: 0.447

Intolerance Scores

• loftool: 0.540
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.38

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.726
• ghis: 0.629

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.533

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Scarb2
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: scarb2a
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: protein targeting to lysosome;receptor-mediated endocytosis;positive regulation of neuron projection development;aminophospholipid transport;regulation of cellular carbohydrate catabolic process;viral entry into host cell;membrane organization;regulation of endosome organization;regulation of glucosylceramidase activity;regulation of lysosome organization
• Cellular component: Golgi membrane;lysosomal membrane;endoplasmic reticulum membrane;plasma membrane;focal adhesion;endosome membrane;membrane;integral component of membrane;clathrin-coated vesicle membrane;endocytic vesicle membrane;late endosome membrane;lysosomal lumen;extracellular exosome
• Molecular function: virus receptor activity;phosphatidylserine binding;transmembrane signaling receptor activity;scavenger receptor activity;protein binding;phospholipid transporter activity;protein transporter activity;cholesterol binding;enzyme binding;phosphatidylcholine binding;protein homodimerization activity