SPTLC3
protein-codingserine palmitoyltransferase long chain base subunit 3
Gene summary
This gene encodes a subunit of the serine palmitoyltransferase complex which catalyzes the rate-limiting step in sphingolipid biosynthesis. This subunit metabolizes lauroyl- and myristoyl-CoA and generates C14 and C16-sphingoid bases. [provided by RefSeq, Mar 2017]
- C20orf38
- SPTLC2L
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~160.1 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 SPTLC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018327.4. 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 | 0 | |||||
| missense | 1 | 71 | 2 | 74 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 1 | 73 | 2 | 0 | 76 |
Highest pathogenic variant AF is 0.000032636093
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060797.2 | 12 | MANE Select | |
| Ensembl | ENSP00000381968.2 | 12 | MANE Select | |
| RefSeq | NP_001336874.1 | 12 | Standard | |
| Ensembl | ENSP00000409760.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sptlc3 | Danio rerio | Structure: motor neuron Quality: morphology abnormal |
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)
- Sphingolipid Metabolism
- Metabolism of lipids
- Metabolism
Biological Process
- sphingolipid biosynthetic process
- sphingoid biosynthetic process
Molecular Function
- serine C-palmitoyltransferase activity
- protein binding
- pyridoxal phosphate binding
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
- serine C-palmitoyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000399002
- Coding exons
- 12
- Length
- 157785
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 125744
- p
- 0.000183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.17 | 255 | 314 | 0.813 | 0.0000169 | 3608 |
| Missense (PolyPhen) | 101 | 133.01 | 0.75932 | 1503 | ||
| Synonymous | -0.955 | 127 | 114 | 1.11 | 0.00000645 | 1061 |
| Loss of Function | 2.25 | 15 | 27.8 | 0.540 | 0.00000151 | 341 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00034 | 0.00033 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00023 | 0.00023 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, while the SPTLC1-SPTLC3-SPTSSB has the ability to use a broader range of acyl-CoAs without apparent preference. {ECO:0000269|PubMed:19416851}.;
Recessive Scores
- pRec
- 0.128
Intolerance Scores
- LoFtool
- 0.252
- RVIS EVS
- -0.22
- RVIS percentile EVS
- 37.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.520
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |