PLEKHF1
protein-codingpleckstrin homology and FYVE domain containing 1, the group of Zinc fingers FYVE-type|Pleckstrin homology domain containing
Gene summary
Enables phosphatidylinositol-3-phosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylinositol-5-phosphate binding activity. Involved in endosome organization; positive regulation of autophagy; and protein localization to plasma membrane. Located in endosome and lysosome. [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 ~10.0 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 PLEKHF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024310.5. 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 | 3 | 5 | ||
| missense | 49 | 3 | 52 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 50 | 4 | 3 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_077286.3 | 1 | MANE Select | |
| Ensembl | ENSP00000389787.2 | 1 | MANE Select | |
| Ensembl | ENSP00000466003.1 | 1 | Standard | |
| Ensembl | ENSP00000464925.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- apoptotic process
- endosome organization
- positive regulation of autophagy
- vesicle organization
- protein localization to plasma membrane
Molecular Function
- protein binding
- phosphatidylinositol-5-phosphate binding
- phosphatidylinositol-3-phosphate binding
- phosphatidylinositol binding
- metal ion binding
Cellular Component
- nucleus
- lysosome
- lysosomal membrane
- endosome
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000436066
- Coding exons
- 1
- Length
- 10402
- Individuals with no LoFs
- 125681
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125698
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.189 | 193 | 201 | 0.962 | 0.0000153 | 1778 |
| Missense (PolyPhen) | 86 | 101.05 | 0.8511 | 858 | ||
| Synonymous | 1.28 | 82 | 98.1 | 0.835 | 0.00000817 | 575 |
| Loss of Function | 1.28 | 4 | 7.86 | 0.509 | 4.24e-7 | 78 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May induce apoptosis through the lysosomal-mitochondrial pathway. Translocates to the lysosome initiating the permeabilization of lysosomal membrane (LMP) and resulting in the release of CTSD and CTSL to the cytoplasm. Triggers the caspase- independent apoptosis by altering mitochondrial membrane permeabilization (MMP) resulting in the release of PDCD8. {ECO:0000269|PubMed:16188880}.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.224
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.728
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |