SPPL3
signal peptide peptidase like 3, the group of Peptidase family A22
Basic information
Region (hg38): 12:120762510-120904358
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPPL3 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 9 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 9 | 0 | 0 |
Variants in SPPL3
This is a list of pathogenic ClinVar variants found in the SPPL3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-120767553-T-C | not specified | Uncertain significance (Dec 01, 2022) | ||
| 12-120768379-T-C | not specified | Uncertain significance (Dec 06, 2024) | ||
| 12-120768382-G-T | not specified | Uncertain significance (Sep 13, 2023) | ||
| 12-120768416-G-C | not specified | Uncertain significance (Dec 19, 2023) | ||
| 12-120769051-T-C | not specified | Uncertain significance (Mar 18, 2024) | ||
| 12-120784486-T-C | not specified | Uncertain significance (Oct 26, 2022) | ||
| 12-120784552-T-C | not specified | Uncertain significance (Nov 10, 2024) | ||
| 12-120810882-A-G | not specified | Uncertain significance (Oct 11, 2024) | ||
| 12-120810884-G-A | not specified | Uncertain significance (Mar 01, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SPPL3 | protein_coding | protein_coding | ENST00000353487 | 11 | 141862 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00344 | 125741 | 0 | 3 | 125744 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.44 | 75 | 218 | 0.345 | 0.0000120 | 2488 |
| Missense in Polyphen | 8 | 64.383 | 0.12426 | 697 | ||
| Synonymous | 0.687 | 74 | 81.9 | 0.903 | 0.00000460 | 779 |
| Loss of Function | 3.79 | 0 | 16.7 | 0.00 | 7.07e-7 | 220 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000108 | 0.0000904 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000897 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries (PubMed:16873890, PubMed:25354954, PubMed:25827571). Acts like a sheddase by mediating the proteolytic release and secretion of active site- containing ectodomains of glycan-modifiying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1 (PubMed:25354954, PubMed:25827571). Catalyzes the intramembrane cleavage of the envelope glycoprotein gp130 and/or the leader peptide gp18LP of the simian foamy virus independent of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). May also have the ability to serve as a shedding protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B of the envelope glycoprotein gp130 (PubMed:23132852). Plays a role in the regulation of cellular glycosylation processes (PubMed:25354954). Required to link T-cell antigen receptor (TCR) and calcineurin- NFAT signaling cascades in lymphocytes by promoting the association of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease-independent manner (PubMed:25384971). {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852, ECO:0000269|PubMed:25354954, ECO:0000269|PubMed:25384971, ECO:0000269|PubMed:25827571}.;
Intolerance Scores
- loftool
- rvis_EVS
- -0.21
- rvis_percentile_EVS
- 38.28
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.673
- ghis
- 0.646
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.404
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sppl3
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- signal peptide processing;membrane protein ectodomain proteolysis;positive regulation of cytosolic calcium ion concentration;positive regulation of protein binding;membrane protein proteolysis;positive regulation of protein dephosphorylation;T cell receptor signaling pathway;positive regulation of calcineurin-NFAT signaling cascade
- Cellular component
- rough endoplasmic reticulum;Golgi apparatus;plasma membrane;membrane;Golgi-associated vesicle membrane;endoplasmic reticulum-Golgi intermediate compartment membrane;intracellular membrane-bounded organelle;integral component of cytoplasmic side of endoplasmic reticulum membrane;integral component of lumenal side of endoplasmic reticulum membrane
- Molecular function
- protein binding;aspartic endopeptidase activity, intramembrane cleaving;protein homodimerization activity