SPNS2

Spinster homolog 2 (Drosophila) is a protein that in humans is encoded by the SPNS2 gene.[5]

SPNS2
Identifiers
Aliases	SPNS2, sphingolipid transporter 2, SLC62A2, DFNB115
External IDs	OMIM: 612584 MGI: 2384936 HomoloGene: 71040 GeneCards: SPNS2
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.2 Start 4,498,881 bp[1] End 4,539,035 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B4 Start 72,451,638 bp[2] End 72,489,904 bp[2]
Gene ontology Molecular function • sphingolipid transporter activity Cellular component • integral component of membrane • vesicle • lysosomal membrane • membrane Biological process • lymphocyte homeostasis • regulation of humoral immune response • regulation of eye pigmentation • lipid transport • lymph node development • B cell homeostasis • bone development • lymphocyte migration • locomotion • transmembrane transport • sphingosine-1-phosphate signaling pathway • sphingolipid metabolic process • T cell homeostasis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	124976	216892
Ensembl	ENSG00000183018	ENSMUSG00000040447
UniProt	Q8IVW8	Q91VM4
RefSeq (mRNA)	NM_001124758	NM_001276383 NM_153060
RefSeq (protein)	NP_001118230	NP_001263312 NP_694700
Location (UCSC)	Chr 17: 4.5 – 4.54 Mb	Chr 11: 72.45 – 72.49 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Model organisms

Spns2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Homozygous Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Abnormal[6]
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal[7]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Abnormal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Abnormal[8]
Clinical chemistry	Abnormal[9]
Plasma immunoglobulins	Normal
Haematology	Abnormal[10]
Peripheral blood lymphocytes	Abnormal[11]
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Abnormal
MicroCT & Quantitative Faxitron	Abnormal
Salmonella infection	Normal[12]
Citrobacter infection	Normal[13]
All tests and analysis from[14][15]

Model organisms have been used in the study of SPNS2 function. A conditional knockout mouse line, called Spns2^{tm1a(KOMP)Wtsi}[16][17] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[18][19][20]

Animals underwent a standardized phenotypic screen to determine the effects of deletion.[14][21] Twenty eight tests were carried out on homozygous mutant mice of both sex and nine significant abnormalities were observed, including an absence of pinna reflex, abnormal eye pigmentation and morphology including cataracts, decreased leukocyte cell number, abnormal brainstem auditory evoked potential, increased bone mineral content and a range of atypical peripheral blood lymphocyte parameters.[14] Males additionally displayed decreased circulating glucose and increased circulating bilirubin levels.[14]

The orthologous protein in zebrafish has been shown to transport sphingosine-1-phosphate (S1P) out of cells during vascular development, and human SPNS2 can transport S1P analogues, including the immunomodulating drug FTY720-P.[22][23]

References

1. GRCh38: Ensembl release 89: ENSG00000183018 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040447 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Spinster homolog 2 (Drosophila)". Retrieved 2011-12-04.
6. "Neurological assessment data for Spns2". Wellcome Trust Sanger Institute.
7. "Dysmorphology data for Spns2". Wellcome Trust Sanger Institute.
8. "Eye morphology data for Spns2". Wellcome Trust Sanger Institute.
9. "Clinical chemistry data for Spns2". Wellcome Trust Sanger Institute.
10. "Haematology data for Spns2". Wellcome Trust Sanger Institute.
11. "Peripheral blood lymphocytes data for Spns2". Wellcome Trust Sanger Institute.
12. "Salmonella infection data for Spns2". Wellcome Trust Sanger Institute.
13. "Citrobacter infection data for Spns2". Wellcome Trust Sanger Institute.
14. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
15. Mouse Resources Portal, Wellcome Trust Sanger Institute.
16. "International Knockout Mouse Consortium".
17. "Mouse Genome Informatics".
18. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
19. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
20. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
21. van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
22. Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N (January 2009). "The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors". Science. 323 (5913): 524–7. Bibcode:2009Sci...323..524K. doi:10.1126/science.1167449. PMID 19074308.
23. Hisano Y, Kobayashi N, Kawahara A, Yamaguchi A, Nishi T (January 2011). "The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter of the phosphorylated form of the immunomodulating agent FTY720". The Journal of Biological Chemistry. 286 (3): 1758–66. doi:10.1074/jbc.M110.171116. PMC 3023470. PMID 21084291.