PLEKHA2
protein-codingpleckstrin homology domain containing A2, the group of Pleckstrin homology domain containing
Gene summary
Enables fibronectin binding activity; laminin binding activity; and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in positive regulation of cell-matrix adhesion. Located in cytoplasm and membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~72.7 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 PLEKHA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021623.2. 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 | 3 | 3 | ||||
| missense | 42 | 3 | 45 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 46 | 3 | 0 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067636.1 | 11 | MANE Select | |
| Ensembl | ENSP00000482228.1 | 11 | MANE Select | |
| RefSeq | NP_001397854.1 | 10 | Standard | |
| Ensembl | ENSP00000429956.1 | 4 | 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
- positive regulation of cell-matrix adhesion
- phosphatidylinositol biosynthetic process
Molecular Function
- fibronectin binding
- protein binding
- PDZ domain binding
- laminin binding
- phosphatidylinositol-3,4-bisphosphate binding
Cellular Component
- nucleus
- cytoplasm
- plasma membrane
- membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000420274
- Coding exons
- 12
- Length
- 72676
- Individuals with no LoFs
- 21281
- Homozygous LoFs
- 103358
- Heterozygous LoFs
- 7
- Defined
- 124646
- p
- 0.587
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.08 | 156 | 248 | 0.629 | 0.0000140 | 2768 |
| Missense (PolyPhen) | 65 | 116.44 | 0.55823 | 1289 | ||
| Synonymous | -0.347 | 95 | 90.8 | 1.05 | 0.00000505 | 818 |
| Loss of Function | 3.74 | 4 | 23.6 | 0.170 | 0.00000126 | 261 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 1.0 | 0.49 | notable |
| Latino/Admixed American | 1.0 | 0.63 | notable |
| Ashkenazi Jewish | 1.0 | 0.71 | notable |
| East Asian | 1.0 | 0.58 | notable |
| Finnish | 1.0 | 0.66 | notable |
| European (Non-Finnish) | 1.0 | 0.56 | notable |
| South Asian | 1.0 | 0.63 | notable |
| Other | 1.0 | 0.64 | notable |
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 (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0962
Essentials
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.714
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |