SMPD2
protein-codingsphingomyelin phosphodiesterase 2
Gene summary
This gene encodes a protein which was initially identified as a sphingomyelinase based on sequence similarity between bacterial sphingomyelinases and a yeast protein. Subsequent studies showed that its biological function is less likely to be as a sphingomyelinase and instead as a lysophospholipase. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SMPD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003080.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 1 | 4 | |||
| missense | 60 | 2 | 62 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 63 | 5 | 1 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003071.2 | 10 | MANE Select | |
| Ensembl | ENSP00000258052.3 | 10 | MANE Select | |
| Ensembl | ENSP00000399731.1 | 4 | Standard | |
| Ensembl | ENSP00000552860.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sphingolipid signaling pathway - Homo sapiens (human)
- Sphingolipid metabolism - Homo sapiens (human)
- TNF alpha Signaling Pathway
- Signal Transduction of S1P Receptor
- Signal Transduction
Biological Process
- sphingomyelin metabolic process
- response to mechanical stimulus
- intracellular signal transduction
- ceramide biosynthetic process
- positive regulation of ceramide biosynthetic process
Molecular Function
- sphingomyelin phosphodiesterase activity
- metal ion binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- caveola
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000258052
- Coding exons
- 10
- Length
- 3157
- Individuals with no LoFs
- 125610
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 138
- Defined
- 125748
- p
- 0.000549
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.143 | 230 | 236 | 0.974 | 0.0000122 | 2754 |
| Missense (PolyPhen) | 47 | 55.455 | 0.84754 | 652 | ||
| Synonymous | -0.129 | 100 | 98.4 | 1.02 | 0.00000542 | 850 |
| Loss of Function | -0.589 | 25 | 22.0 | 1.14 | 0.00000101 | 239 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00086 | 0.00086 | rare |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00071 | 0.00065 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00053 | 0.00053 | rare |
| South Asian | 0.0010 | 0.0010 | notable |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Converts sphingomyelin to ceramide. Hydrolyze 1-acyl-2- lyso-sn-glycero-3-phosphocholine (lyso-PC) and 1-O-alkyl-2-lyso- sn-glycero-3-phosphocholine (lyso-platelet-activating factor). The physiological substrate seems to be Lyso-PAF.;
Recessive Scores
- pRec
- 0.293
Intolerance Scores
- LoFtool
- 0.664
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.795
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |