NSMAF
protein-codingneutral sphingomyelinase activation associated factor, the group of WD repeat domain containing|GRAM domain containing|BEACH domain containing
Gene summary
This gene encodes a WD-repeat protein that binds the cytoplasmic sphingomyelinase activation domain of the 55kD tumor necrosis factor receptor. This protein is required for TNF-mediated activation of neutral sphingomyelinase and may play a role in regulating TNF-induced cellular responses such as inflammation. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~76.3 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 NSMAF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003580.4. 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 | 2 | |||
| missense | 118 | 1 | 119 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 131 | 2 | 0 | 133 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003571.2 | 31 | MANE Select | |
| Ensembl | ENSP00000038176.3 | 31 | MANE Select | |
| RefSeq | NP_001138244.1 | 31 | Standard | |
| RefSeq | NP_001399917.1 | 24 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nsmaf | Danio rerio | Structure: leukocyte Quality: cellular motility abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sphingolipid signaling pathway - Homo sapiens (human)
- TNF alpha Signaling Pathway
- Signal Transduction
- ceramide signaling pathway
- TNFR1-mediated ceramide production
Biological Process
- ceramide metabolic process
- signal transduction
- positive regulation of apoptotic process
- positive regulation of catalytic activity
- positive regulation of ceramide biosynthetic process
Molecular Function
- protein binding
- sphingomyelin phosphodiesterase activator activity
Cellular Component
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000427130
- Coding exons
- 31
- Length
- 76341
- Individuals with no LoFs
- 125625
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 122
- Defined
- 125748
- p
- 0.000489
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 415 | 507 | 0.819 | 0.0000259 | 6237 |
| Missense (PolyPhen) | 159 | 201.61 | 0.78866 | 2478 | ||
| Synonymous | 1.55 | 162 | 189 | 0.857 | 0.0000109 | 1718 |
| Loss of Function | 3.52 | 28 | 56.6 | 0.495 | 0.00000248 | 721 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.00049 | 0.00049 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.00088 | 0.00088 | rare |
| European (Non-Finnish) | 0.00046 | 0.00046 | rare |
| South Asian | 0.00060 | 0.00056 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Couples the p55 TNF-receptor (TNF-R55 / TNFR1) to neutral sphingomyelinase (N-SMASE). Specifically binds to the N- smase activation domain of TNF-R55. May regulate ceramide production by N-SMASE.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.381
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 44.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.494
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |