SMPDL3B
protein-codingsphingomyelin phosphodiesterase acid like 3B
Gene summary
Enables phosphoric diester hydrolase activity. Predicted to be involved in negative regulation of inflammatory response; negative regulation of toll-like receptor signaling pathway; and obsolete membrane lipid catabolic process. Located in extracellular exosome and obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.2 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 SMPDL3B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014474.4. 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 | 1 | 1 | 1 | 3 | ||
| missense | 77 | 7 | 1 | 85 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 81 | 8 | 2 | 91 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055289.2 | 8 | MANE Select | |
| Ensembl | ENSP00000363001.3 | 8 | MANE Select | |
| RefSeq | NP_001009568.1 | 7 | Standard | |
| RefSeq | NP_001291508.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- sphingomyelin catabolic process
- inflammatory response
- biological_process
- negative regulation of toll-like receptor signaling pathway
- innate immune response
Molecular Function
- sphingomyelin phosphodiesterase activity
- phosphoric diester hydrolase activity
- hydrolase activity, acting on glycosyl bonds
- metal ion binding
Cellular Component
- extracellular space
- plasma membrane
- anchored component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373894
- Coding exons
- 8
- Length
- 24165
- Individuals with no LoFs
- 125664
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 84
- Defined
- 125748
- p
- 0.000334
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.690 | 251 | 284 | 0.885 | 0.0000170 | 2981 |
| Missense (PolyPhen) | 84 | 96.507 | 0.87041 | 1140 | ||
| Synonymous | 0.920 | 112 | 125 | 0.895 | 0.00000876 | 904 |
| Loss of Function | 0.681 | 15 | 18.1 | 0.827 | 9.43e-7 | 191 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00076 | 0.00076 | rare |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.00040 | 0.00040 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Lipid-modulating phosphodiesterase (PubMed:26095358). Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling (By similarity). {ECO:0000250|UniProtKB:P58242, ECO:0000269|PubMed:26095358}.;
Intolerance Scores
- RVIS EVS
- -0.02
- RVIS percentile EVS
- 52.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.138
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |