SORCS3

Chr 10

sortilin related VPS10 domain containing receptor 3

Also known as: SORCS

NCBI Gene: 22986ENSG00000156395UniProt: Q9UPU3

This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
13
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.47
LOEUF
DN
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.47LOEUF
pLI 0.000
Z-score 4.98
OE 0.32 (0.22–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.52Z-score
OE missense 0.83 (0.78–0.89)
542 obs / 651.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.32 (0.22–0.47)
0≤0.351.4
Missense OE?0.83 (0.78–0.89)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 20 / 62.5Missense obs/exp: 542 / 651.3Syn Z: -0.15

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SORCS3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients