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

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 (98 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	15	3	19
missense		1	102	6	2	111
nonsense		1				1
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)			2			2
Total	0	3	105	21	5

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
		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

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

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