GPD1L
protein-codingglycerol-3-phosphate dehydrogenase 1 like
Gene summary
The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~63.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0015263
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0011001
Submitter: ClinGen
Inheritance Pattern: AD
Disease ID:MONDO:0012728
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: Unknown
Disease ID:MONDO:0012728
Submitter: Genomics England PanelApp
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular
Intervention: Cardiovascular; Pharmacogenomic
Rationale: Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GPD1L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015141.4. 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 | 120 | 1 | 121 | |||
| missense | 196 | 19 | 215 | |||
| nonsense | 5 | 5 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 6 | 1 | 7 | |||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 213 | 140 | 1 | 354 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055956.1 | 8 | MANE Select | |
| Ensembl | ENSP00000282541.6 | 8 | MANE Select | |
| Ensembl | ENSP00000408770.1 | 5 | Standard | |
| Ensembl | ENSP00000392199.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycerophospholipid metabolism - Homo sapiens (human)
- Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
- Metabolism of lipids
- Metabolism
- Glycerophospholipid biosynthesis
Biological Process
- action potential
- regulation of heart rate
- carbohydrate metabolic process
- phosphatidic acid biosynthetic process
- positive regulation of sodium ion transport
Molecular Function
- glycerol-3-phosphate dehydrogenase [NAD+] activity
- sodium channel regulator activity
- protein homodimerization activity
- ion channel binding
- NAD binding
Cellular Component
- cytosol
- plasma membrane
- glycerol-3-phosphate dehydrogenase complex
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000282541
- Coding exons
- 8
- Length
- 63025
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 157 | 200 | 0.786 | 0.0000114 | 2307 |
| Missense (PolyPhen) | 55 | 77.775 | 0.70717 | 913 | ||
| Synonymous | 0.0118 | 78 | 78.1 | 0.998 | 0.00000518 | 688 |
| Loss of Function | 2.39 | 5 | 15.0 | 0.334 | 7.04e-7 | 184 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium current; cardiac sodium current may also be reduced due to alterations of NAD(H) balance induced by DPD1L. {ECO:0000269|PubMed:19666841, ECO:0000269|PubMed:19745168}.;
Recessive Scores
- pRec
- 0.174
Intolerance Scores
- LoFtool
- 0.504
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.966
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |