SGPP1
protein-codingsphingosine-1-phosphate phosphatase 1, the group of Sphingosine-1-phosphate phosphatases
Gene summary
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that regulates diverse biologic processes. SGPP1 catalyzes the degradation of S1P via salvage and recycling of sphingosine into long-chain ceramides (Mandala et al., 2000 [PubMed 10859351]; Le Stunff et al., 2007 [PubMed 17895250]).[supplied by OMIM, Jun 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SGPP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030791.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 64 | 3 | 67 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 64 | 4 | 0 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_110418.1 | 3 | MANE Select | |
| Ensembl | ENSP00000247225.6 | 3 | MANE Select | |
| Ensembl | ENSP00000526026.1 | 2 | Standard | |
| Ensembl | ENSP00000526026.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sphingolipid signaling pathway - Homo sapiens (human)
- Sphingolipid metabolism - Homo sapiens (human)
- Metabolism of lipids
- Metabolism
- Sphingolipid de novo biosynthesis
Biological Process
- sphinganine-1-phosphate metabolic process
- sphingosine metabolic process
- dephosphorylation
- sphingolipid biosynthetic process
- extrinsic apoptotic signaling pathway
Molecular Function
- sphingosine-1-phosphate phosphatase activity
- dihydrosphingosine-1-phosphate phosphatase activity
Cellular Component
- nucleus
- nucleoplasm
- endoplasmic reticulum membrane
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000247225
- Coding exons
- 3
- Length
- 43826
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.646 | 193 | 220 | 0.877 | 0.0000104 | 2798 |
| Missense (PolyPhen) | 61 | 87.778 | 0.69494 | 1048 | ||
| Synonymous | -0.701 | 97 | 88.6 | 1.09 | 0.00000420 | 947 |
| Loss of Function | 1.38 | 8 | 13.5 | 0.595 | 7.26e-7 | 159 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically dephosphorylates sphingosine 1-phosphate (S1P), dihydro-S1P, and phyto-S1P. Does not act on ceramide 1- phoshate, lysophosphatidic acid or phosphatidic acid. Regulates the intracellular levels of the bioactive sphingolipid metabolite S1P that regulates diverse biological processes acting both as an extracellular receptor ligand or as an intracellular second messenger (PubMed:12815058, PubMed:11756451). Involved in efficient ceramide synthesis from exogenous sphingoid bases. Converts S1P to sphingosine, which is readily metabolized to ceramide via ceramide synthase. In concert with sphingosine kinase 2 (SphK2), recycles sphingosine into ceramide though a phosphorylation/dephosphorylation cycle. Regulates intracellular ceramide levels, which in turn regulate apoptosis (By similarity). Via S1P levels, modulates resting tone, intracellular Ca(2+) and myogenic vasoconstriction in resistance arteries (PubMed:18583713). Also involved in unfolded protein response (UPR) and ER stress-induced autophagy via regulation of intracellular S1P levels (PubMed:20798685). {ECO:0000250|UniProtKB:Q9JI99, ECO:0000269|PubMed:11756451, ECO:0000269|PubMed:12815058, ECO:0000269|PubMed:18583713, ECO:0000269|PubMed:20798685}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.146
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.858
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |