SPNS2

SPNS lysolipid transporter 2, sphingosine-1-phosphate, the group of Solute carrier family 63, sphingosine phosphate transporters

Basic information

Region (hg38): 17:4498881-4539035

Links

ENSG00000183018

∙ NCBI:124976 ∙ OMIM:612584 ∙ HGNC:26992 ∙ Uniprot:Q8IVW8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hearing loss, autosomal recessive 115 (Moderate), mode of inheritance: AR
hearing loss, autosomal recessive 115 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive, 115	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	30973865

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPNS2 gene.

not_specified (83 variants)
SPNS2-related_disorder (24 variants)
not_provided (17 variants)
Hearing_loss,_autosomal_recessive_115 (5 variants)
Inborn_genetic_diseases (2 variants)
Sensorineural_hearing_loss_disorder (2 variants)
Hearing_impairment (1 variants)
Microcephaly-intellectual_disability-sensorineural_hearing_loss-epilepsy-abnormal_muscle_tone_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPNS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001124758.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				15 clinvar	3 clinvar	18
missense		1 clinvar	85 clinvar	6 clinvar	2 clinvar	94
nonsense		1 clinvar				1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	0	3	85	21	5

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPNS2	protein_coding	protein_coding	ENST00000329078	12	40198

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000124	0.990	124692	0	33	124725	0.000132

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0679	315	312	1.01	0.0000203	3457
Missense in Polyphen		105	122.03	0.86043		1252
Synonymous	-4.15	203	140	1.45	0.0000100	1205
Loss of Function	2.31	12	24.3	0.494	0.00000128	260

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000233	0.000233
Ashkenazi Jewish	0.000101	0.0000994
East Asian	0.000167	0.000167
Finnish	0.0000932	0.0000928
European (Non-Finnish)	0.000134	0.000133
Middle Eastern	0.000167	0.000167
South Asian	0.0000981	0.0000980
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

Function: FUNCTION: Sphingolipid transporter required for migration of myocardial precursors. Transports sphingosine 1-phosphate (S1P), a secreted lipid mediator that plays critical roles in cardiovascular, immunological, and neural development and function. Mediates the export of S1P from cells in the extraembryonic yolk syncytial layer (YSL), thereby regulating myocardial precursor migration. {ECO:0000269|PubMed:19074308}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

loftool: 0.572
rvis_EVS: -0.98
rvis_percentile_EVS: 8.85

Haploinsufficiency Scores

pHI: 0.364
hipred: N
hipred_score: 0.492
ghis: 0.499

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.270

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Spns2
Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; pigmentation 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: spns2
Affected structure: median fin
Phenotype tag: abnormal
Phenotype quality: blistered

Gene ontology

Biological process: B cell homeostasis;regulation of humoral immune response;sphingosine-1-phosphate receptor signaling pathway;sphingolipid metabolic process;lipid transport;T cell homeostasis;regulation of eye pigmentation;lymph node development;transmembrane transport;bone development;lymphocyte migration
Cellular component: integral component of membrane
Molecular function: sphingolipid transporter activity