SORT1
sortilin 1
Basic information
Region (hg38): 1:109309568-109397918
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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 | 8 | |||||
| missense | 20 | 26 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | 2 | |||
| non coding | 0 | |||||
| Total | 0 | 0 | 20 | 7 | 7 |
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) | ||
| 1-109316858-C-G | not specified | Uncertain significance (Apr 09, 2024) | ||
| 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) | ||
| 1-109324934-T-A | not specified | Uncertain significance (Jun 07, 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) | ||
| 1-109342016-C-A | not specified | Uncertain significance (Jun 05, 2024) | ||
| 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) |
GnomAD
Source:
| 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:
- 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