PLEKHH1
protein-codingpleckstrin homology, MyTH4 and FERM domain containing H1, the group of Pleckstrin homology domain containing|FERM domain containing
Gene summary
Predicted to be located in cytoskeleton. [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 ~56.3 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 PLEKHH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020715.3. 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 | 4 | 1 | 5 | |||
| missense | 201 | 14 | 215 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 211 | 16 | 0 | 227 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065766.1 | 28 | MANE Select | |
| Ensembl | ENSP00000330278.5 | 28 | MANE Select | |
| Ensembl | ENSP00000453699.1 | 2 | Standard | |
| Ensembl | ENSP00000453343.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Cellular Component
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329153
- Coding exons
- 28
- Length
- 56312
- Individuals with no LoFs
- 124538
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 142
- Defined
- 124680
- p
- 0.000570
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.96 | 611 | 763 | 0.800 | 0.0000437 | 8744 |
| Missense (PolyPhen) | 116 | 161.26 | 0.71934 | 1854 | ||
| Synonymous | 1.41 | 277 | 309 | 0.898 | 0.0000179 | 2752 |
| Loss of Function | 4.71 | 27 | 69.3 | 0.390 | 0.00000351 | 794 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00046 | 0.00045 | rare |
| Latino/Admixed American | 0.00071 | 0.00070 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00085 | 0.00083 | rare |
| Finnish | 0.00075 | 0.00074 | rare |
| European (Non-Finnish) | 0.00052 | 0.00050 | rare |
| South Asian | 0.00057 | 0.00052 | rare |
| Other | 0.00083 | 0.00083 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.0838
Intolerance Scores
- LoFtool
- 0.797
- RVIS EVS
- 1.26
- RVIS percentile EVS
- 93.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.136
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |