SPCS3

Chr 4

signal peptidase complex subunit 3

Also known as: PRO3567, SPC22, SPC22/23, SPC23, SPC3, YLR066W

NCBI Gene: 60559 ENSG00000129128 UniProt: P61009

SPCS3 encodes an essential component of the signal peptidase complex that cleaves N-terminal signal sequences from nascent proteins as they enter the endoplasmic reticulum lumen. The gene is highly constrained against loss-of-function variants (pLI 0.82, LOEUF 0.53), suggesting mutations would cause severe disease, though specific associated disorders have not yet been established in the literature. Given its essential role in protein processing and high constraint scores, pathogenic variants would likely affect multiple organ systems.

ResearchSummary from RefSeq, UniProt

Involved in signal peptide processing and viral protein processing. Located in endoplasmic reticulum membrane. Part of signal peptidase complex. [provided by Alliance of Genome Resources, Jul 2025]

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.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.53

LOEUF

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Mechanism

Some data sources returned errors (1)

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