PHLDA2
protein-codingpleckstrin homology like domain family A member 2, the group of Pleckstrin homology domain containing
Gene summary
This gene is located in a cluster of imprinted genes on chromosome 11p15.5, which is considered to be an important tumor suppressor gene region. Alterations in this region may be associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene has been shown to be imprinted, with preferential expression from the maternal allele in placenta and liver. [provided by RefSeq, Oct 2010]
- TSSC3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.1 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 PHLDA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003311.4. 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 | ||||
| missense | 29 | 3 | 32 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 29 | 4 | 0 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003302.1 | 1 | MANE Select | |
| Ensembl | ENSP00000319231.4 | 1 | MANE Select | |
| Ensembl | ENSP00000520820.1 | 2 | Standard | |
| Ensembl | ENSP00000806633.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- apoptotic process
Cellular Component
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314222
- Coding exons
- 1
- Length
- 1183
- Individuals with no LoFs
- 119428
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 119430
- p
- 0.00000837
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.125 | 86 | 89.3 | 0.963 | 0.00000402 | 973 |
| Missense (PolyPhen) | 27 | 31.998 | 0.8438 | 345 | ||
| Synonymous | 0.152 | 38 | 39.2 | 0.969 | 0.00000186 | 318 |
| Loss of Function | 0.685 | 1 | 2.06 | 0.485 | 8.78e-8 | 26 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000067 | 0.000067 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in regulating placenta growth. May act via its PH domain that competes with other PH domain-containing proteins, thereby preventing their binding to membrane lipids (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.307
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.932
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |