SPHK1
protein-codingsphingosine kinase 1
Gene summary
The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Phosphorylation of this protein alters its catalytic activity and promotes its translocation to the plasma membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.3 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 SPHK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001142601.2. 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 | 3 | 4 | |||
| missense | 55 | 1 | 1 | 57 | ||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 59 | 2 | 4 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001136073.1 | 5 | MANE Select | |
| Ensembl | ENSP00000465726.2 | 5 | MANE Select | |
| RefSeq | NP_001136074.1 | 5 | Standard | |
| RefSeq | NP_001342068.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sphk1 | Danio rerio | Structure: heart Quality: split bilaterally abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- VEGF signaling pathway - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Apelin signaling pathway - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
Biological Process
- blood vessel development
- sphingosine-1-phosphate receptor signaling pathway
- protein folding
- sphingosine metabolic process
- inflammatory response
Molecular Function
- magnesium ion binding
- DNA binding
- NAD+ kinase activity
- protein binding
- calmodulin binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000323374
- Coding exons
- 6
- Length
- 11277
- Individuals with no LoFs
- 125122
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 613
- Defined
- 125737
- p
- 0.00245
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.489 | 279 | 303 | 0.921 | 0.0000184 | 2930 |
| Missense (PolyPhen) | 45 | 56.979 | 0.78976 | 551 | ||
| Synonymous | -1.24 | 152 | 134 | 1.14 | 0.00000835 | 1052 |
| Loss of Function | 0.491 | 11 | 12.9 | 0.852 | 6.33e-7 | 150 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00069 | 0.00068 | rare |
| Latino/Admixed American | 0.0014 | 0.0014 | notable |
| Ashkenazi Jewish | 0.0010 | 0.00099 | rare |
| East Asian | 0.000061 | 0.000054 | rare |
| Finnish | 0.0016 | 0.0016 | notable |
| European (Non-Finnish) | 0.0032 | 0.0032 | notable |
| South Asian | 0.0042 | 0.0042 | notable |
| Other | 0.0033 | 0.0033 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro- sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N- dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. {ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23602659}.;
Recessive Scores
- pRec
- 0.236
Intolerance Scores
- LoFtool
- 0.821
- RVIS EVS
- -0.22
- RVIS percentile EVS
- 37.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |