SORT1

sortilin 1

Basic information

Region (hg38): 1:109309567-109397918

Links

ENSG00000134243 ∙ NCBI:6272 ∙ OMIM:602458 ∙ HGNC:11186 ∙ Uniprot:Q99523 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SORT1 gene.

• Inborn genetic diseases (12 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SORT1 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		1
missense			12	3	2	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	12	4	2

Variants in SORT1

This is a list of pathogenic ClinVar variants found in the SORT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-109314301-G-A		not specified	Uncertain significance (Sep 27, 2021)
1-109314740-G-A		SORT1-related disorder	Likely benign (Feb 26, 2020)
1-109316859-C-T		SORT1-related disorder	Likely benign (Aug 20, 2019)
1-109316860-G-A		not specified	Uncertain significance (Mar 12, 2024)
1-109316863-C-T			Benign (Jun 14, 2018)
1-109323051-A-C		not specified	Uncertain significance (Feb 12, 2024)
1-109325051-G-A		SORT1-related disorder	Benign (Aug 20, 2019)
1-109326996-T-G		not specified	Uncertain significance (Aug 13, 2021)
1-109327015-G-A		SORT1-related disorder	Benign (Apr 09, 2019)
1-109327547-T-C		not specified	Uncertain significance (Mar 01, 2024)
1-109336271-T-C			Likely benign (Oct 01, 2022)
1-109336296-G-A		not specified	Uncertain significance (Sep 20, 2023)
1-109340761-G-A		SORT1-related disorder	Likely benign (Dec 06, 2019)
1-109340843-C-T		not specified	Uncertain significance (Apr 05, 2023)
1-109342050-C-A			Benign (Jan 12, 2018)
1-109342131-T-C		not specified	Uncertain significance (Jul 05, 2023)
1-109342153-T-G		SORT1-related disorder	Benign (Oct 17, 2019)
1-109345782-C-T		not specified	Uncertain significance (Nov 28, 2023)
1-109345810-T-C			Likely benign (Nov 01, 2022)
1-109345851-C-T		not specified	Uncertain significance (Feb 28, 2024)
1-109345861-C-T		not specified	Uncertain significance (Sep 01, 2021)
1-109347507-T-A		not specified	Uncertain significance (Feb 10, 2022)
1-109347508-A-C		not specified	Uncertain significance (Feb 10, 2022)
1-109350971-C-T		not specified	Uncertain significance (May 04, 2023)
1-109354481-A-G		SORT1-related disorder	Benign (Oct 17, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SORT1	protein_coding	protein_coding	ENST00000256637	20	88382

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000128	125736	0	11	125747	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.10	288	407	0.707	0.0000214	5396
Missense in Polyphen		45	92.675	0.48557		1121
Synonymous	0.800	142	155	0.918	0.00000861	1635
Loss of Function	5.52	4	43.2	0.0927	0.00000225	522

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000910	0.0000910
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000930	0.0000924
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000657	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi. {ECO:0000269|PubMed:10085125, ECO:0000269|PubMed:11331584, ECO:0000269|PubMed:11390366, ECO:0000269|PubMed:12209882, ECO:0000269|PubMed:12598608, ECO:0000269|PubMed:14657016, ECO:0000269|PubMed:14985763, ECO:0000269|PubMed:15313463, ECO:0000269|PubMed:15930396, ECO:0000269|PubMed:15987945}.
• Disease: DISEASE: Note=A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.
• Pathway: Neurotrophin signaling pathway - Homo sapiens (human);Lysosome - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;BDNF;p75(NTR)-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.285

Intolerance Scores

• loftool: 0.389
• rvis_EVS: 0.38
• rvis_percentile_EVS: 75.51

Haploinsufficiency Scores

• pHI: 0.859
• hipred: Y
• hipred_score: 0.806
• ghis: 0.473

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.761

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sort1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; vision/eye 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); 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); 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)

Gene ontology

• Biological process: ossification;Golgi to endosome transport;endocytosis;G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;multicellular organism development;endosome to lysosome transport;extrinsic apoptotic signaling pathway via death domain receptors;regulation of gene expression;myotube differentiation;vesicle organization;endosome transport via multivesicular body sorting pathway;response to insulin;nerve growth factor signaling pathway;negative regulation of fat cell differentiation;glucose import;neurotrophin TRK receptor signaling pathway;plasma membrane to endosome transport;negative regulation of lipoprotein lipase activity;positive regulation of epithelial cell apoptotic process
• Cellular component: lysosomal membrane;early endosome;endoplasmic reticulum membrane;Golgi apparatus;cytosol;plasma membrane;clathrin-coated pit;cell surface;endosome membrane;integral component of membrane;clathrin-coated vesicle;trans-Golgi network transport vesicle;dendrite;cytoplasmic vesicle membrane;cytoplasmic vesicle;nuclear membrane;Golgi cisterna membrane;neuronal cell body;perinuclear region of cytoplasm
• Molecular function: protein binding;nerve growth factor receptor activity;enzyme binding;neurotensin receptor activity, non-G protein-coupled;nerve growth factor binding