SPHK2

sphingosine kinase 2

Basic information

Region (hg38): 19:48619290-48630717

Links

ENSG00000063176 ∙ NCBI:56848 ∙ OMIM:607092 ∙ HGNC:18859 ∙ Uniprot:Q9NRA0 ∙ 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 SPHK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPHK2 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				4	2	6
missense			54	2	3	59
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	54	7	5

Variants in SPHK2

This is a list of pathogenic ClinVar variants found in the SPHK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-48620524-C-A		not specified	Uncertain significance (Dec 12, 2023)
19-48620528-T-C		not specified	Uncertain significance (Sep 17, 2021)
19-48625911-C-T			Likely benign (Nov 01, 2022)
19-48625917-C-A		not specified	Uncertain significance (May 21, 2024)
19-48625928-G-C		not specified	Uncertain significance (Jun 18, 2021)
19-48625961-T-C		not specified	Uncertain significance (Apr 20, 2024)
19-48625963-G-A		not specified	Uncertain significance (Mar 15, 2024)
19-48625976-C-T		not specified	Uncertain significance (Oct 02, 2023)
19-48625997-C-T		not specified	Uncertain significance (Jan 09, 2024)
19-48626035-G-A		not specified	Uncertain significance (Feb 12, 2024)
19-48626041-C-T		not specified	Uncertain significance (Jun 30, 2023)
19-48626060-C-T		not specified	Uncertain significance (Jul 28, 2021)
19-48626063-C-T		not specified	Uncertain significance (Jan 29, 2024)
19-48626077-A-C		not specified	Uncertain significance (Jan 26, 2022)
19-48626084-G-A		not specified	Uncertain significance (Jun 14, 2022)
19-48626100-T-G			Likely benign (Mar 01, 2023)
19-48626113-C-T		not specified	Uncertain significance (Aug 12, 2021)
19-48626114-G-A		not specified	Uncertain significance (Jul 14, 2021)
19-48626128-C-G		not specified	Uncertain significance (Apr 27, 2022)
19-48626143-T-A		not specified	Uncertain significance (Nov 06, 2023)
19-48626162-G-A		not specified	Uncertain significance (Dec 14, 2023)
19-48626168-G-A		not specified	Uncertain significance (Nov 01, 2022)
19-48626233-C-T		not specified	Uncertain significance (Apr 09, 2024)
19-48626237-G-A		not specified	Uncertain significance (Feb 16, 2023)
19-48626272-G-T		not specified	Uncertain significance (Feb 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPHK2	protein_coding	protein_coding	ENST00000245222	6	11427

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.28e-7	0.821	125695	0	52	125747	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	358	435	0.823	0.0000306	4022
Missense in Polyphen		98	146.79	0.6676		1308
Synonymous	-0.290	211	206	1.03	0.0000151	1564
Loss of Function	1.48	14	21.4	0.655	0.00000126	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00105	0.00104
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000162	0.000139
European (Non-Finnish)	0.000167	0.000158
Middle Eastern	0.000109	0.000109
South Asian	0.000270	0.000261
Other	0.00	0.00

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- dihydrosphingosine, D-erythro-sphingosine and L-threo- dihydrosphingosine. Binds phosphoinositides. {ECO:0000269|PubMed:19168031}.
• 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;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Sphingolipid Metabolism;Signal Transduction of S1P Receptor;Metabolism of Spingolipids in ER and Golgi apparatus;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism;sphingosine and sphingosine-1-phosphate metabolism;Sphingosine 1-phosphate (S1P) pathway;Ceramide signaling pathway;IL12-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.795
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.57

Haploinsufficiency Scores

• pHI: 0.0898
• hipred: N
• hipred_score: 0.272
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sphk2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland phenotype; embryo phenotype; immune system 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); 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; 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)

Zebrafish Information Network

• Gene name: sphk2
• Affected structure: median fin
• Phenotype tag: abnormal
• Phenotype quality: blistered

Gene ontology

• Biological process: blood vessel development;sphingosine-1-phosphate receptor signaling pathway;sphinganine-1-phosphate biosynthetic process;brain development;female pregnancy;cell population proliferation;positive regulation of cell population proliferation;sphingolipid biosynthetic process;negative regulation of apoptotic process;sphingosine biosynthetic process;lipid phosphorylation
• Cellular component: lysosomal membrane;cytosol;membrane;intracellular membrane-bounded organelle
• Molecular function: NAD+ kinase activity;protein binding;ATP binding;sphinganine kinase activity;Ras GTPase binding;D-erythro-sphingosine kinase activity;sphingosine-1-phosphate receptor activity