SPHK1

sphingosine kinase 1

Basic information

Region (hg38): 17:76376584-76387860

Links

ENSG00000176170 ∙ NCBI:8877 ∙ OMIM:603730 ∙ HGNC:11240 ∙ Uniprot:Q9NYA1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPHK1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPHK1 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					2	2
missense			29	2	1	32
nonsense						0
start loss						0
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			1			1
Total	0	0	30	3	3

Variants in SPHK1

This is a list of pathogenic ClinVar variants found in the SPHK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-76385160-G-A		not specified	Uncertain significance (Jan 19, 2024)
17-76385481-C-A			Likely benign (Aug 13, 2018)
17-76385481-C-T		not specified	Uncertain significance (Feb 05, 2024)
17-76385498-C-G		not specified	Uncertain significance (Oct 09, 2024)
17-76385531-T-G		not specified	Uncertain significance (Jan 24, 2024)
17-76385540-C-G		not specified	Uncertain significance (Dec 04, 2024)
17-76385550-G-T		not specified	Uncertain significance (Nov 25, 2024)
17-76385986-G-C			Benign (Jun 14, 2018)
17-76386008-C-T		not specified	Uncertain significance (Oct 06, 2021)
17-76386117-C-T		not specified	Uncertain significance (Aug 08, 2022)
17-76386123-C-T		not specified	Uncertain significance (Sep 03, 2024)
17-76386226-C-G		not specified	Uncertain significance (Mar 21, 2023)
17-76386430-C-G		not specified	Uncertain significance (May 28, 2024)
17-76386444-C-G		not specified	Uncertain significance (Nov 08, 2022)
17-76386445-C-T		not specified	Uncertain significance (Dec 20, 2023)
17-76386810-G-A		not specified	Uncertain significance (Apr 20, 2023)
17-76386862-G-A		not specified	Uncertain significance (Aug 05, 2024)
17-76386864-C-T		not specified	Uncertain significance (Oct 12, 2024)
17-76386897-C-T		not specified	Uncertain significance (Oct 22, 2021)
17-76386899-C-T			Benign (Feb 08, 2018)
17-76386915-C-A		not specified	Uncertain significance (Jun 01, 2023)
17-76386984-C-T		not specified	Uncertain significance (Nov 19, 2022)
17-76387020-T-C		not specified	Uncertain significance (Nov 07, 2022)
17-76387026-CG-C			Likely benign (Dec 31, 2019)
17-76387028-T-C			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPHK1	protein_coding	protein_coding	ENST00000323374	6	11277

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.03e-7	0.328	125122	2	613	125737	0.00245

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.489	279	303	0.921	0.0000184	2930
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00214	0.00212
Ashkenazi Jewish	0.000995	0.000993
East Asian	0.0000606	0.0000544
Finnish	0.00163	0.00162
European (Non-Finnish)	0.00318	0.00317
Middle Eastern	0.0000606	0.0000544
South Asian	0.00425	0.00419
Other	0.00327	0.00326

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Signal Transduction of S1P Receptor;Metabolism of Spingolipids in ER and Golgi apparatus;Signal Transduction;phospholipids as signalling intermediaries;VEGFA-VEGFR2 Pathway;Metabolism of lipids;Metabolism of proteins;Chaperonin-mediated protein folding;Metabolism;Association of TriC/CCT with target proteins during biosynthesis;Fibroblast growth factor-1;Glycosphingolipid metabolism;Beta3 integrin cell surface interactions;Protein folding;Signaling by VEGF;Sphingolipid de novo biosynthesis;Sphingolipid metabolism;sphingosine and sphingosine-1-phosphate metabolism;Signaling by Receptor Tyrosine Kinases;Fc-epsilon receptor I signaling in mast cells;S1P1 pathway;PDGFR-beta signaling pathway;Sphingosine 1-phosphate (S1P) pathway;VEGFR2 mediated cell proliferation (Consensus)

Recessive Scores

• pRec: 0.236

Intolerance Scores

• loftool: 0.821
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.54

Haploinsufficiency Scores

• pHI: 0.134
• hipred: Y
• hipred_score: 0.505
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sphk1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; embryo phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; endocrine/exocrine gland phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: sphk1
• Affected structure: heart
• Phenotype tag: abnormal
• Phenotype quality: split bilaterally

Gene ontology

• Biological process: blood vessel development;sphingosine-1-phosphate receptor signaling pathway;protein folding;sphingosine metabolic process;inflammatory response;signal transduction;brain development;positive regulation of peptidyl-threonine phosphorylation;regulation of tumor necrosis factor-mediated signaling pathway;calcium-mediated signaling;sphingolipid biosynthetic process;positive regulation of cell growth;positive regulation of cell migration;positive regulation of protein ubiquitination;regulation of interleukin-1 beta production;intracellular signal transduction;negative regulation of apoptotic process;positive regulation of angiogenesis;positive regulation of mitotic cell cycle;positive regulation of smooth muscle contraction;sphingosine biosynthetic process;sphingoid catabolic process;lipid phosphorylation;positive regulation of fibroblast proliferation;positive regulation of NF-kappaB transcription factor activity;positive regulation of NIK/NF-kappaB signaling
• Cellular component: nucleus;cytoplasm;cytosol;plasma membrane
• Molecular function: magnesium ion binding;DNA binding;NAD+ kinase activity;protein binding;calmodulin binding;ATP binding;sphinganine kinase activity;D-erythro-sphingosine kinase activity;sphingosine-1-phosphate receptor activity;protein phosphatase 2A binding