SGPL1

sphingosine-1-phosphate lyase 1

Basic information

Region (hg38): 10:70815904-70895816

Links

ENSG00000166224 ∙ NCBI:8879 ∙ OMIM:603729 ∙ HGNC:10817 ∙ Uniprot:O95470 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephrotic syndrome 14 (Moderate), mode of inheritance: AR
• nephrotic syndrome 14 (Strong), mode of inheritance: AR
• nephrotic syndrome 14 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
RENI syndrome	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Endocrine	Individuals have been described with immunodeficiency, including recurrent bacterial infections, and awareness may allow preventative measures and early and aggressive treatment of infections; Individuals have been described with hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with adrenal insufficiency, and awareness may allow early diagnosis and management	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Endocrine; Genitourinary; Neurologic; Renal	28165339; 28165343; 28181337; 36873630

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SGPL1 gene.

• not provided (202 variants)
• Pterin-4 alpha-carbinolamine dehydratase 1 deficiency (63 variants)
• Inborn genetic diseases (18 variants)
• Nephrotic syndrome 14 (15 variants)
• BH4-Deficient Hyperphenylalaninemia (6 variants)
• not specified (3 variants)
• Nephrotic syndrome (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SGPL1 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			2	42	4	48
missense		2	80	5	1	88
nonsense	5					5
start loss						0
frameshift	2					2
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			5	7	1	13
non coding	4	6	23	57	29	119
Total	11	9	106	104	34

Highest pathogenic variant AF is 0.0000197

Variants in SGPL1

This is a list of pathogenic ClinVar variants found in the SGPL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-70816859-T-C			Likely benign (Dec 18, 2023)
10-70816859-T-TA		Nephrotic syndrome 14	Pathogenic (Aug 24, 2023)
10-70816887-C-A			Likely benign (Apr 22, 2022)
10-70816895-G-C			Likely benign (Jan 16, 2024)
10-70844458-C-T			Likely benign (Jun 15, 2021)
10-70844477-C-T			Uncertain significance (May 25, 2022)
10-70844489-A-G			Likely benign (Jan 22, 2024)
10-70844506-G-T		Nephrotic syndrome 14	Benign (Feb 01, 2024)
10-70844513-C-G			Uncertain significance (Apr 26, 2022)
10-70844517-A-C			Likely benign (Dec 22, 2023)
10-70844518-A-G			Uncertain significance (Jun 13, 2022)
10-70844531-AT-A		Nephrotic syndrome 14	Likely pathogenic (Sep 17, 2018)
10-70844532-T-C			Likely benign (Jul 31, 2023)
10-70844577-A-G			Likely benign (May 09, 2023)
10-70844579-G-A			Pathogenic (Sep 15, 2022)
10-70844587-G-A			Uncertain significance (Jan 29, 2024)
10-70844589-G-T			Likely benign (Nov 18, 2022)
10-70844598-G-A		SGPL1-related disorder	Likely benign (Jan 24, 2024)
10-70844610-G-A			Pathogenic (Feb 11, 2022)
10-70844611-G-T			Pathogenic (Nov 15, 2023)
10-70844616-T-C			Likely benign (Sep 12, 2022)
10-70844627-T-G			Uncertain significance (May 09, 2023)
10-70844637-G-C			Uncertain significance (Jul 23, 2022)
10-70844650-G-C			Likely benign (Nov 16, 2023)
10-70844658-T-C			Likely benign (Nov 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SGPL1	protein_coding	protein_coding	ENST00000373202	14	65214

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00363	0.996	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	227	318	0.713	0.0000170	3726
Missense in Polyphen		53	112.91	0.46941		1301
Synonymous	0.285	111	115	0.966	0.00000618	1072
Loss of Function	3.45	10	30.6	0.326	0.00000155	381

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000133	0.000133
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000878	0.000878
European (Non-Finnish)	0.0000985	0.0000967
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis. {ECO:0000269|PubMed:11018465, ECO:0000269|PubMed:14570870, ECO:0000269|PubMed:24809814, ECO:0000269|PubMed:28165339}.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Sphingolipid Metabolism;Kennedy pathway from Sphingolipids;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism;Sphingosine 1-phosphate (S1P) pathway (Consensus)

Recessive Scores

• pRec: 0.432

Intolerance Scores

• loftool: 0.593
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.34

Haploinsufficiency Scores

• pHI: 0.165
• hipred: Y
• hipred_score: 0.601
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.554

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sgpl1
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; renal/urinary system phenotype; skeleton phenotype; respiratory system 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); normal phenotype; reproductive system phenotype; digestive/alimentary phenotype; immune system phenotype

Gene ontology

• Biological process: luteinization;vasculogenesis;ameboidal-type cell migration;kidney development;fatty acid metabolic process;sphingolipid metabolic process;ceramide metabolic process;spermatogenesis;androgen metabolic process;estrogen metabolic process;post-embryonic development;fibroblast migration;hemopoiesis;sphingolipid biosynthetic process;sphingolipid catabolic process;Leydig cell differentiation;regulation of multicellular organism growth;platelet-derived growth factor receptor signaling pathway;skeletal system morphogenesis;roof of mouth development;face morphogenesis;apoptotic signaling pathway
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of endoplasmic reticulum membrane
• Molecular function: protein binding;sphinganine-1-phosphate aldolase activity;carboxy-lyase activity;pyridoxal phosphate binding