SMPD3

sphingomyelin phosphodiesterase 3

Basic information

Region (hg38): 16:68358327-68448508

Links

ENSG00000103056 ∙ NCBI:55512 ∙ OMIM:605777 ∙ HGNC:14240 ∙ Uniprot:Q9NY59 ∙ 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 SMPD3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMPD3 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						0
missense			46	1		47
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	46	1	0

Variants in SMPD3

This is a list of pathogenic ClinVar variants found in the SMPD3 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-68361213-T-G		not specified	Uncertain significance (Oct 12, 2021)
16-68361243-A-G		not specified	Uncertain significance (Nov 15, 2024)
16-68361271-C-T		not specified	Uncertain significance (Apr 12, 2024)
16-68361655-C-T		not specified	Uncertain significance (Apr 15, 2024)
16-68361685-C-T		not specified	Uncertain significance (Oct 04, 2022)
16-68361686-G-A		not specified	Uncertain significance (May 21, 2024)
16-68363530-C-T		not specified	Uncertain significance (Jul 09, 2021)
16-68363539-C-T		not specified	Uncertain significance (Jan 22, 2024)
16-68363546-G-C		not specified	Uncertain significance (Nov 24, 2024)
16-68363812-C-T		not specified	Uncertain significance (Aug 17, 2021)
16-68364819-G-A		not specified	Uncertain significance (Aug 28, 2023)
16-68364891-C-T		not specified	Uncertain significance (Sep 22, 2022)
16-68365044-C-T		not specified	Uncertain significance (Aug 21, 2024)
16-68365056-C-T		not specified	Uncertain significance (Jan 09, 2024)
16-68365082-C-T		not specified	Uncertain significance (Jun 04, 2024)
16-68370897-C-T		not specified	Uncertain significance (Jul 10, 2024)
16-68370902-C-T		not specified	Uncertain significance (May 22, 2023)
16-68370934-C-T		not specified	Uncertain significance (Aug 09, 2021)
16-68370995-C-T		not specified	Uncertain significance (Jan 17, 2024)
16-68371005-C-T		not specified	Uncertain significance (Sep 04, 2024)
16-68371155-C-T		not specified	Uncertain significance (Jan 02, 2024)
16-68371166-C-T		not specified	Uncertain significance (Jan 02, 2024)
16-68371179-C-T		not specified	Uncertain significance (Jul 20, 2021)
16-68371190-T-C		not specified	Uncertain significance (Feb 16, 2023)
16-68371194-C-A		not specified	Uncertain significance (Aug 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMPD3	protein_coding	protein_coding	ENST00000219334	7	90361

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.594	0.406	125723	0	12	125735	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	356	420	0.848	0.0000282	4181
Missense in Polyphen		96	156.71	0.61261		1588
Synonymous	-1.34	228	204	1.12	0.0000156	1368
Loss of Function	3.66	5	24.6	0.203	0.00000140	254

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000166	0.0000905
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000445	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Probably acts as a regulator of postnatal development and participates in bone and dentin mineralization. {ECO:0000269|PubMed:10823942, ECO:0000269|PubMed:14741383, ECO:0000269|PubMed:15051724}.
• Pathway: Sphingolipid metabolism - Homo sapiens (human);Signal Transduction;Metabolism of lipids;sphingomyelin metabolism/ceramide salvage;Metabolism;Glycosphingolipid metabolism;TNFR1-mediated ceramide production;TNF signaling;Death Receptor Signalling;Glycosphingolipid metabolism;Sphingolipid metabolism;TNFalpha;Ceramide signaling pathway (Consensus)

Recessive Scores

• pRec: 0.183

Intolerance Scores

• loftool: 0.152
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.12

Haploinsufficiency Scores

• pHI: 0.351
• hipred: Y
• hipred_score: 0.687
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.984

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smpd3
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; reproductive system phenotype; 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); respiratory system phenotype; skeleton phenotype

Gene ontology

• Biological process: hematopoietic progenitor cell differentiation;sphingomyelin metabolic process;sphingomyelin catabolic process;cell cycle;peptide hormone secretion;positive regulation of exosomal secretion;positive regulation of ceramide biosynthetic process
• Cellular component: Golgi cis cisterna;Golgi membrane;cytoplasm;plasma membrane
• Molecular function: sphingomyelin phosphodiesterase activity;protein binding;metal ion binding