SORCS2

protein-coding

sortilin related VPS10 domain containing receptor 2, the group of MicroRNA protein coding host genes

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_020777.3

Inheritance

—

ClinVar variants

U:228B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr4:7,192,538-7,742,827

External References & Databases

Ensembl (ENSG00000184985)

Transcript & Mutation Effects

hg38 • Region Span ~550.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SORCS2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 356

not providedTotal: 20

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020777.3. 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				5 clinvar	9 clinvar	14
missense			223 clinvar	6 clinvar	1 clinvar	230
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	228	11	10	249

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020777.3	RefSeq	NP_065828.2	27	MANE Select
ENST00000507866.6	Ensembl	ENSP00000422185.2	27	MANE Select
ENST00000505529.1	Ensembl	ENSP00000424194.1	3	Standard
ENST00001136087.1	Ensembl	ENSP00000813512.1	27	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

neuropeptide signaling pathway

Molecular Function

neuropeptide receptor activity

Cellular Component

membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000507866
Coding exons: 27
Length: 550290
Individuals with no LoFs: 124617
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 124641
p: 0.0000963

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.585	589	630	0.934	0.0000412	7349
Missense (PolyPhen)		169	215.27	0.78506		2269
Synonymous	-2.56	347	291	1.19	0.0000221	2356
Loss of Function	5.01	16	56.7	0.282	0.00000267	648

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000039	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0996

Intolerance Scores

LoFtool: 0.693
RVIS EVS: -0.41
RVIS percentile EVS: 25.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.384

Gene Damage Prediction

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