SORCS1

protein-coding

sortilin related VPS10 domain containing receptor 1

Gene summary

This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. Two of the five family members (sortilin and sortilin-related receptor) are synthesized as preproproteins; it is not yet known if this encoded protein is also a preproprotein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_052918.5

Inheritance

—

ClinVar variants

U:166B:15

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr10:106,573,663-107,164,706

External References & Databases

Ensembl (ENSG00000108018)

Transcript & Mutation Effects

hg38 • Region Span ~591.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SORCS1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 171

not providedTotal: 11

Prostate cancerTotal: 1

Alzheimer disease 6Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052918.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	5 clinvar	4 clinvar	11
missense			163 clinvar	4 clinvar	2 clinvar	169
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	166	9	6	181

Highest pathogenic variant AF is 6.840694e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052918.5	RefSeq	NP_443150.3	26	MANE Select
ENST00000263054.11	Ensembl	ENSP00000263054.5	26	MANE Select
NM_001013031.3	RefSeq	NP_001013049.1	27	Standard
NM_001206569.2	RefSeq	NP_001193498.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ectoderm Differentiation

Biological Process

neuropeptide signaling pathway

Molecular Function

protein binding
neuropeptide receptor activity

Cellular Component

membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344440
Coding exons: 27
Length: 590872
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.30	566	660	0.857	0.0000355	7771
Missense (PolyPhen)		142	218.52	0.64984		2643
Synonymous	0.625	250	263	0.951	0.0000152	2353
Loss of Function	5.98	15	68.3	0.220	0.00000370	757

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.136

Intolerance Scores

LoFtool: 0.644
RVIS EVS: -1.14
RVIS percentile EVS: 6.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.255

Gene Damage Prediction

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