PLEKHA1
protein-codingpleckstrin homology domain containing A1, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes
Gene summary
This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~57.7 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 PLEKHA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001001974.4. 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 | 3 | 1 | 4 | |||
| missense | 44 | 4 | 48 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 54 | 5 | 0 | 59 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001001974.1 | 11 | MANE Select | |
| Ensembl | ENSP00000357986.3 | 11 | MANE Select | |
| RefSeq | NP_001182537.1 | 11 | Standard | |
| RefSeq | NP_001317107.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- Metabolism
- BCR
- Synthesis of PIPs at the plasma membrane
- Class I PI3K signaling events
Biological Process
- luteinization
- phosphatidylinositol biosynthetic process
- spermatogenesis
- androgen metabolic process
- estrogen metabolic process
Molecular Function
- protein binding
- PDZ domain binding
- phosphatidylinositol-3,4-bisphosphate binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368990
- Coding exons
- 11
- Length
- 57656
- Individuals with no LoFs
- 125658
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 90
- Defined
- 125748
- p
- 0.000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.656 | 207 | 235 | 0.880 | 0.0000133 | 2663 |
| Missense (PolyPhen) | 81 | 105.66 | 0.76662 | 1261 | ||
| Synonymous | 0.0292 | 82 | 82.3 | 0.996 | 0.00000504 | 750 |
| Loss of Function | 2.55 | 10 | 23.3 | 0.429 | 0.00000120 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00040 | 0.00040 | rare |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds specifically to phosphatidylinositol 3,4- diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane. {ECO:0000269|PubMed:11001876, ECO:0000269|PubMed:11513726, ECO:0000269|PubMed:14516276}.;
Recessive Scores
- pRec
- 0.165
Intolerance Scores
- LoFtool
- 0.845
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.719
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |