PLEKHN1
protein-codingpleckstrin homology domain containing N1, the group of Pleckstrin homology domain containing
Gene summary
Enables phospholipid binding activity. Involved in 3'-UTR-mediated mRNA destabilization; positive regulation of apoptotic process; and response to hypoxia. Located in cytoskeleton; mitochondrial membrane; and plasma membrane. [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 ~9.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0015364
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLEKHN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032129.3. 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 | 153 | 29 | 4 | 186 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 156 | 30 | 4 | 190 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115505.2 | 16 | MANE Select | |
| Ensembl | ENSP00000368720.3 | 16 | MANE Select | |
| RefSeq | NP_001153656.1 | 15 | Standard | |
| RefSeq | NP_001354481.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EGFR1
Biological Process
- response to hypoxia
- positive regulation of apoptotic process
- 3'-UTR-mediated mRNA destabilization
Molecular Function
- phosphatidylserine binding
- protein binding
- phosphatidic acid binding
- cardiolipin binding
- phosphatidylinositol phosphate binding
Cellular Component
- mitochondrion
- cytoskeleton
- plasma membrane
- mitochondrial membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379410
- Coding exons
- 16
- Length
- 9369
- Individuals with no LoFs
- 125455
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 177
- Defined
- 125633
- p
- 0.000709
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.80 | 480 | 381 | 1.26 | 0.0000241 | 3802 |
| Missense (PolyPhen) | 135 | 97.727 | 1.3814 | 1147 | ||
| Synonymous | -2.47 | 216 | 175 | 1.24 | 0.0000114 | 1323 |
| Loss of Function | 1.01 | 25 | 31.1 | 0.805 | 0.00000157 | 332 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0027 | 0.0026 | notable |
| Latino/Admixed American | 0.00021 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00058 | 0.00051 | rare |
| South Asian | 0.0029 | 0.0020 | notable |
| Other | 0.00074 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Controls the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR, in cooperation with the RNA stabilizer ELAVL1 (PubMed:29180010). Decreases the stability of the leptin mRNA by antagonizing the function of ELAVL1 by inducing its atypical recruitment from the nucleus to the cytosol (By similarity). Binds to cardiolipin (CL), phosphatidic acid (PA), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidylserine (PS) (PubMed:18191643). Promotes apoptosis by enhancing BAX-BAK hetro-oligomerization via interaction with BID in colon cancer cells (PubMed:29531808) (By similarity). {ECO:0000250|UniProtKB:Q8C886, ECO:0000269|PubMed:18191643, ECO:0000269|PubMed:29180010, ECO:0000269|PubMed:29531808}.;
Recessive Scores
- pRec
- 0.0962
Intolerance Scores
- LoFtool
- 0.926
- RVIS EVS
- 0.9
- RVIS percentile EVS
- 89.33
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.259
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |