SPCS3
Signal Peptidase Complex Subunit 3
Gene Information Card
| Symbol | SPCS3 |
|---|---|
| Full Name | Signal Peptidase Complex Subunit 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q34.2 |
| NCBI Gene ID | 60559 ncbi.nlm.nih.gov/gene/60559 |
| Ensembl ID | ENSG00000138698 |
| UniProt ID | Q9P0S3 |
| OMIM ID | 618342 |
| HGNC ID | 28719 |
| Aliases | SPC3, SPC22/23, MGC2650 |
Description
SPCS3 encodes subunit 3 of the signal peptidase complex (SPC), an integral membrane protein complex located in the endoplasmic reticulum (ER). The SPC cleaves signal peptides from nascent secretory and membrane proteins during co-translational translocation. SPCS3 is essential for proper protein trafficking and secretion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive microcephaly | Loss-of-function mutations in SPCS3 impair signal peptide cleavage, leading to ER stress and reduced neuronal proliferation | PMID: 31730861 |
| Neurodevelopmental disorder with microcephaly and seizures | Biallelic SPCS3 variants disrupt SPC assembly and function, causing abnormal brain development | ClinVar: SCV001422456 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Heart | 7.6 | Low |
| Testis | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.8 | High expression |
| HeLa | 11.2 | Medium expression |
| SH-SY5Y | 13.5 | High expression |
| HepG2 | 9.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.335G>A (p.Arg112His) | Missense | Rare | Loss of SPC3 stability and complex assembly |
| c.487C>T (p.Arg163*) | Nonsense | Rare | Premature truncation, loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein production |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function variants cause autosomal recessive microcephaly and neurodevelopmental disorders.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • signal peptidase activity | • endoplasmic reticulum membrane |
| • proteolysis | • signal peptide processing |
| • protein targeting to ER |
Pathways
• Signal Peptidase Complex
• Protein processing in endoplasmic reticulum
• Secretory pathway
Protein Summary
SPCS3 is a 22-23 kDa subunit of the signal peptidase complex. It localizes to the ER membrane and is required for the catalytic activity of the complex. The protein contains a conserved domain that stabilizes the interaction with other SPC subunits. Loss of SPCS3 leads to defective signal peptide removal and ER stress.
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