LYPLA1
protein-codinglysophospholipase 1, the group of Depalmitoylases
Gene summary
This gene encodes a member of the alpha/beta hydrolase superfamily. The encoded protein functions as a homodimer, exhibiting both depalmitoylating as well as lysophospholipase activity, and may be involved in Ras localization and signaling. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 4, 6, and 7. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.7 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 LYPLA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006330.4. 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 | ||||
| missense | 25 | 1 | 1 | 27 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 32 | 2 | 1 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006321.1 | 9 | MANE Select | |
| Ensembl | ENSP00000320043.3 | 9 | MANE Select | |
| RefSeq | NP_001266285.1 | 8 | Standard | |
| RefSeq | NP_001266286.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycerophospholipid metabolism - Homo sapiens (human)
- Choline metabolism in cancer - Homo sapiens (human)
- Phospholipid Biosynthesis
- Metabolism of nitric oxide
- eNOS activation
Biological Process
- protein depalmitoylation
- fatty acid metabolic process
- negative regulation of Golgi to plasma membrane protein transport
- regulation of nitric-oxide synthase activity
Molecular Function
- lysophospholipase activity
- palmitoyl-(protein) hydrolase activity
- lipase activity
- carboxylic ester hydrolase activity
Cellular Component
- cytoplasm
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316963
- Coding exons
- 9
- Length
- 55640
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125747
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.03 | 88 | 120 | 0.734 | 0.00000593 | 1482 |
| Missense (PolyPhen) | 17 | 32.457 | 0.52378 | 405 | ||
| Synonymous | -0.416 | 45 | 41.6 | 1.08 | 0.00000221 | 434 |
| Loss of Function | 1.32 | 9 | 14.4 | 0.625 | 7.08e-7 | 171 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000066 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has depalmitoylating activity toward KCNMA1. Has low lysophospholipase activity. {ECO:0000269|PubMed:20418879, ECO:0000269|PubMed:22399288}.;
Recessive Scores
- pRec
- 0.162
Intolerance Scores
- LoFtool
- 0.723
- RVIS EVS
- 0.39
- RVIS percentile EVS
- 76.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.954
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |