SPPL2A

Chr 15q21.2

signal peptide peptidase like 2A

Aliases:: IMP3, PSL2
MANE:: ENST00000261854.10

OMIM: 608238 ↗NCBI: 84888 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

SPPL2A · Q8TCT8

v62025-08-01

Predicted Aligned Error matrix for SPPL2A — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

79.4/ 100

Confident

520 residues

Confidence breakdown

Very high(≥ 90)37%
Confident(70–90)39%
Low(50–70)12%
Very low(< 50)11%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

immunodeficiency 86
0.44
hereditary spastic paraplegia 51
0.33
Alzheimer disease
0.33
Abnormality of refraction
0.30
alcohol drinking
0.25
seasonal allergic rhinitis
0.25
osteoarthritis, knee
0.24
medical procedure
0.24
ovarian neoplasm
0.23
Hyperhidrosis
0.22

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Signal peptide peptidase-like 2A

Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing (PubMed:16829951, PubMed:16829952, PubMed:17557115, PubMed:17965014). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952). Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD) (PubMed:17557115). Essential for degradation of the invariant chain CD74 that plays a central role in the function of antigen-presenting cells in the immune system (By similarity). Plays a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus envelope glycoprotein gp130 independently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852)