SAMD8
protein-codingsterile alpha motif domain containing 8, the group of Sterile alpha motif domain containing
Gene summary
Predicted to enable ceramide cholinephosphotransferase activity; ceramide phosphoethanolamine synthase activity; and sphingomyelin synthase activity. Involved in ceramide biosynthetic process and regulation of ceramide biosynthetic process. Located in endoplasmic reticulum membrane. [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 ~82.5 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 SAMD8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001174156.2. 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 | 1 | 25 | 26 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 26 | 1 | 0 | 29 |
Highest pathogenic variant AF is 0.000006570475
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001167627.1 | 5 | MANE Select | |
| Ensembl | ENSP00000438042.1 | 5 | MANE Select | |
| RefSeq | NP_653261.1 | 4 | Standard | |
| Ensembl | ENSP00000361772.3 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- sphingomyelin metabolism/ceramide salvage
- Metabolism
- Sphingolipid de novo biosynthesis
- Sphingolipid metabolism
Biological Process
- sphingomyelin biosynthetic process
- sphingolipid biosynthetic process
- ceramide biosynthetic process
- ceramide phosphoethanolamine biosynthetic process
- regulation of ceramide biosynthetic process
Molecular Function
- ceramide phosphoethanolamine synthase activity
- molecular_function
- sphingomyelin synthase activity
- ceramide cholinephosphotransferase activity
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- cytosol
- integral component of plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000542569
- Coding exons
- 5
- Length
- 82538
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125746
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.89 | 101 | 222 | 0.455 | 0.0000109 | 2751 |
| Missense (PolyPhen) | 24 | 82.059 | 0.29247 | 1050 | ||
| Synonymous | 0.459 | 72 | 77.1 | 0.934 | 0.00000383 | 784 |
| Loss of Function | 2.47 | 8 | 19.9 | 0.402 | 0.00000131 | 205 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.000070 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sphingomyelin synthases synthesize sphingolipids through transfer of a phosphatidyl head group on to the primary hydroxyl of ceramide. SAMD8 is an endoplasmic reticulum (ER) transferase that has no sphingomyelin synthase activity but can convert phosphatidylethanolamine (PE) and ceramide to ceramide phosphoethanolamine (CPE) albeit with low product yield. Appears to operate as a ceramide sensor to control ceramide homeostasis in the endoplasmic reticulum rather than a converter of ceramides. Seems to be critical for the integrity of the early secretory pathway. {ECO:0000269|PubMed:19506037}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.357
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.141
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |