PLEKHA8
protein-codingpleckstrin homology domain containing A8, the group of Pleckstrin homology domain containing
Gene summary
Enables several functions, including cerebroside transfer activity; phosphatidylinositol-4-phosphate binding activity; and small GTPase binding activity. Involved in ER to Golgi ceramide transport and globoside biosynthetic process. Located in nucleoplasm and trans-Golgi network. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~103.1 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 PLEKHA8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001197026.2. 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 | 1 | 1 | 2 | |||
| missense | 64 | 1 | 65 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 72 | 2 | 0 | 74 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001183955.1 | 14 | MANE Select | |
| Ensembl | ENSP00000397947.1 | 14 | MANE Select | |
| RefSeq | NP_001183956.1 | 14 | Standard | |
| RefSeq | NP_001337902.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- Metabolism
- Synthesis of PIPs at the plasma membrane
- PI Metabolism
- Phospholipid metabolism
Biological Process
- phosphatidylinositol biosynthetic process
- lipid transport
- protein transport
- ER to Golgi ceramide transport
- ceramide transport
Molecular Function
- lipid binding
- glycolipid transporter activity
- glycolipid binding
- phosphatidylinositol-4-phosphate binding
- ceramide binding
Cellular Component
- Golgi membrane
- nucleoplasm
- Golgi apparatus
- trans-Golgi network
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000449726
- Coding exons
- 14
- Length
- 103077
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125748
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.937 | 217 | 259 | 0.836 | 0.0000125 | 3407 |
| Missense (PolyPhen) | 78 | 109.31 | 0.71358 | 1371 | ||
| Synonymous | -0.242 | 98 | 95.0 | 1.03 | 0.00000476 | 951 |
| Loss of Function | 1.74 | 18 | 27.9 | 0.644 | 0.00000131 | 372 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00017 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cargo transport protein that is required for apical transport from the Golgi complex. Transports AQP2 from the trans- Golgi network (TGN) to sites of AQP2 phosphorylation. Mediates the non-vesicular transport of glucosylceramide (GlcCer) from the trans-Golgi network (TGN) to the plasma membrane and plays a pivotal role in the synthesis of complex glycosphingolipids. Binding of both phosphatidylinositol 4-phosphate (PIP) and ARF1 are essential for the GlcCer transfer ability. Also required for primary cilium formation, possibly by being involved in the transport of raft lipids to the apical membrane, and for membrane tubulation. {ECO:0000269|PubMed:15107860, ECO:0000269|PubMed:16103222, ECO:0000269|PubMed:17687330}.;
Intolerance Scores
- LoFtool
- 0.314
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 69.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.671
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |