SPHK2

protein-coding

sphingosine kinase 2

Gene summary

This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_020126.5

Inheritance

—

ClinVar variants

U:121B:19

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr19:48,619,291-48,630,717

External References & Databases

Ensembl (ENSG00000063176)

Transcript & Mutation Effects

hg38 • Region Span ~11.4 kb

Loading mutation effect viewer...

GenCC 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 SPHK2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 124

not providedTotal: 12

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020126.5. 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			2 clinvar	6 clinvar	2 clinvar	10
missense			118 clinvar	8 clinvar	3 clinvar	129
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	121	14	5	140

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020126.5	RefSeq	NP_064511.2	6	MANE Select
ENST00000245222.9	Ensembl	ENSP00000245222.3	6	MANE Select
NM_001204158.3	RefSeq	NP_001191087.1	6	Standard
NM_001204159.3	RefSeq	NP_001191088.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sphk2	Danio rerio	Structure: median fin Quality: blistered abnormal

Gene / Model

Organism

Observed Phenotype

sphk2

Danio rerio

Structure: median fin

Quality: blistered

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
sphinganine-1-phosphate biosynthetic process
brain development
female pregnancy

Molecular Function

NAD+ kinase activity
protein binding
ATP binding
sphinganine kinase activity
Ras GTPase binding

Cellular Component

lysosomal membrane
cytosol
membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000245222
Coding exons: 6
Length: 11427
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125747
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	358	435	0.823	0.0000306	4022
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00081	0.00080	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00016	0.00014	rare
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.00027	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.795
RVIS EVS: 0.13
RVIS percentile EVS: 63.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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