PLEKHH3
protein-codingpleckstrin homology, MyTH4 and FERM domain containing H3, the group of FERM domain containing|Pleckstrin homology domain containing
Gene summary
Located in obsolete extracellular space. [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 ~9.1 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 PLEKHH3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024927.5. 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 | 2 | 2 | ||||
| missense | 147 | 2 | 1 | 150 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 152 | 4 | 1 | 157 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079203.4 | 13 | MANE Select | |
| Ensembl | ENSP00000468678.1 | 13 | MANE Select | |
| RefSeq | NP_001398041.1 | 13 | Standard | |
| Ensembl | ENSP00000293349.6 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- signal transduction
Cellular Component
- extracellular space
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000591022
- Coding exons
- 13
- Length
- 9117
- Individuals with no LoFs
- 125673
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 64
- Defined
- 125737
- p
- 0.000255
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.69 | 344 | 444 | 0.774 | 0.0000296 | 4851 |
| Missense (PolyPhen) | 36 | 49.101 | 0.73319 | 557 | ||
| Synonymous | 2.24 | 171 | 213 | 0.805 | 0.0000142 | 1818 |
| Loss of Function | 2.77 | 16 | 33.2 | 0.482 | 0.00000182 | 343 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000060 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00013 | 0.000099 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.0019 | 0.0019 | notable |
| European (Non-Finnish) | 0.00013 | 0.00011 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.0968
Intolerance Scores
- LoFtool
- 0.223
- RVIS EVS
- -0.96
- RVIS percentile EVS
- 9.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.249
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |