SGPP1

sphingosine-1-phosphate phosphatase 1, the group of Sphingosine-1-phosphate phosphatases

Basic information

Region (hg38): 14:63684216-63728065

Links

ENSG00000126821 ∙ NCBI:81537 ∙ OMIM:612826 ∙ HGNC:17720 ∙ Uniprot:Q9BX95 ∙ 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 SGPP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SGPP1 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				1		1
missense			37	3		40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	37	4	0

Variants in SGPP1

This is a list of pathogenic ClinVar variants found in the SGPP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-63686172-T-C		not specified	Uncertain significance (Dec 01, 2022)
14-63686184-C-T		not specified	Uncertain significance (Jun 22, 2024)
14-63686223-C-T		not specified	Uncertain significance (Apr 25, 2023)
14-63686238-G-A		not specified	Uncertain significance (Dec 02, 2022)
14-63686314-T-A		not specified	Uncertain significance (May 28, 2024)
14-63686319-A-G		not specified	Uncertain significance (Apr 12, 2023)
14-63686330-C-G		not specified	Uncertain significance (Nov 13, 2024)
14-63686365-G-A		not specified	Uncertain significance (Nov 03, 2022)
14-63686434-A-C		not specified	Uncertain significance (Aug 12, 2022)
14-63686470-C-T		not specified	Uncertain significance (Oct 12, 2021)
14-63686518-A-G		not specified	Uncertain significance (Apr 27, 2022)
14-63686545-T-C		not specified	Uncertain significance (Oct 26, 2022)
14-63686577-T-G		not specified	Uncertain significance (Oct 22, 2021)
14-63686583-T-C		not specified	Uncertain significance (Dec 02, 2022)
14-63727274-T-C		not specified	Uncertain significance (Jan 17, 2023)
14-63727281-G-A		not specified	Uncertain significance (Jun 07, 2024)
14-63727296-T-C		not specified	Uncertain significance (May 15, 2024)
14-63727358-A-G		not specified	Uncertain significance (Sep 12, 2023)
14-63727436-A-G		not specified	Uncertain significance (Apr 07, 2023)
14-63727476-G-C		not specified	Likely benign (Apr 07, 2023)
14-63727510-G-C		not specified	Uncertain significance (Apr 07, 2023)
14-63727543-G-C		not specified	Uncertain significance (Apr 07, 2023)
14-63727556-C-T		not specified	Likely benign (Apr 07, 2023)
14-63727580-C-T		not specified	Likely benign (Apr 07, 2023)
14-63727581-G-A		not specified	Uncertain significance (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SGPP1	protein_coding	protein_coding	ENST00000247225	3	43826

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000139	0.868	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.646	193	220	0.877	0.0000104	2798
Missense in Polyphen		61	87.778	0.69494		1048
Synonymous	-0.701	97	88.6	1.09	0.00000420	947
Loss of Function	1.38	8	13.5	0.595	7.26e-7	159

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000361	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specifically dephosphorylates sphingosine 1-phosphate (S1P), dihydro-S1P, and phyto-S1P. Does not act on ceramide 1- phoshate, lysophosphatidic acid or phosphatidic acid. Regulates the intracellular levels of the bioactive sphingolipid metabolite S1P that regulates diverse biological processes acting both as an extracellular receptor ligand or as an intracellular second messenger (PubMed:12815058, PubMed:11756451). Involved in efficient ceramide synthesis from exogenous sphingoid bases. Converts S1P to sphingosine, which is readily metabolized to ceramide via ceramide synthase. In concert with sphingosine kinase 2 (SphK2), recycles sphingosine into ceramide though a phosphorylation/dephosphorylation cycle. Regulates intracellular ceramide levels, which in turn regulate apoptosis (By similarity). Via S1P levels, modulates resting tone, intracellular Ca(2+) and myogenic vasoconstriction in resistance arteries (PubMed:18583713). Also involved in unfolded protein response (UPR) and ER stress-induced autophagy via regulation of intracellular S1P levels (PubMed:20798685). {ECO:0000250|UniProtKB:Q9JI99, ECO:0000269|PubMed:11756451, ECO:0000269|PubMed:12815058, ECO:0000269|PubMed:18583713, ECO:0000269|PubMed:20798685}.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Metabolism of lipids;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism;sphingosine and sphingosine-1-phosphate metabolism;Sphingosine 1-phosphate (S1P) pathway (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.146
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

• pHI: 0.341
• hipred: Y
• hipred_score: 0.642
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.858

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sgpp1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands 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); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: sphinganine-1-phosphate metabolic process;sphingosine metabolic process;dephosphorylation;sphingolipid biosynthetic process;extrinsic apoptotic signaling pathway;intrinsic apoptotic signaling pathway
• Cellular component: nucleus;nucleoplasm;endoplasmic reticulum membrane;plasma membrane;integral component of membrane
• Molecular function: sphingosine-1-phosphate phosphatase activity;dihydrosphingosine-1-phosphate phosphatase activity