PPP4R3A
protein-codingprotein phosphatase 4 regulatory subunit 3A, the group of Armadillo like helical domain containing
Gene summary
Predicted to enable protein phosphatase activator activity. Predicted to be involved in DNA damage response and regulation of double-strand break repair. Predicted to act upstream of or within positive regulation of gluconeogenesis and protein dephosphorylation. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2025]
- KIAA2010
- SMEK1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.0 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 PPP4R3A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001366432.2. 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 | 1 | 1 | 2 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 8 | 0 | 1 | 9 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001353361.1 | 15 | MANE Select | |
| Ensembl | ENSP00000450883.1 | 15 | MANE Select | |
| RefSeq | NP_001271209.1 | 15 | Standard | |
| RefSeq | NP_001271210.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glucagon signaling pathway - Homo sapiens (human)
- IGF-Ncore
- Integrated Breast Cancer Pathway
Cellular Component
- nucleoplasm
- cytoplasm
- microtubule organizing center
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000554684
- Coding exons
- 15
- Length
- 52944
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125723
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.64 | 215 | 427 | 0.504 | 0.0000216 | 5413 |
| Missense (PolyPhen) | 86 | 217.5 | 0.39541 | 2815 | ||
| Synonymous | -1.44 | 177 | 154 | 1.15 | 0.00000780 | 1520 |
| Loss of Function | 5.41 | 3 | 39.9 | 0.0752 | 0.00000215 | 505 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulatory subunit of serine/threonine-protein phosphatase 4. May regulate the activity of PPP4C at centrosomal microtubule organizing centers. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AFX phosphorylated on 'Ser-140' (gamma-H2AFX) generated during DNA replication and required for DNA DSB repair. {ECO:0000269|PubMed:18614045}.;
Intolerance Scores
- RVIS EVS
- -0.65
- RVIS percentile EVS
- 16.36