PPP4R4
protein-codingprotein phosphatase 4 regulatory subunit 4, the group of Armadillo like helical domain containing|Protein phosphatase 4 regulatory subunits|Cilia and flagella associated
Gene summary
The protein encoded by this gene is a HEAT-like repeat-containing protein. The HEAT repeat is a tandemly repeated, 37-47 amino acid long module occurring in a number of cytoplasmic proteins. Arrays of HEAT repeats form a rod-like helical structure and appear to function as protein-protein interaction surfaces. The repeat-containing region of this protein has some similarity to the constant regulatory domain of the protein phosphatase 2A PR65/A subunit. The encoded protein binds protein serine/threonine phosphatase 4c in the cytoplasm. [provided by RefSeq, Jan 2017]
- KIAA1622
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~133.6 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 PPP4R4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_058237.2. 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 | 1 | 1 | ||||
| missense | 98 | 1 | 99 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 100 | 2 | 0 | 102 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_478144.1 | 25 | MANE Select | |
| Ensembl | ENSP00000305924.3 | 25 | MANE Select | |
| RefSeq | NP_001335071.1 | 23 | Standard | |
| RefSeq | NP_001335072.1 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- blastocyst hatching
- negative regulation of phosphoprotein phosphatase activity
- regulation of protein serine/threonine phosphatase activity
Molecular Function
- protein binding
- protein phosphatase regulator activity
Cellular Component
- cytoplasm
- cytosol
- protein serine/threonine phosphatase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000304338
- Coding exons
- 25
- Length
- 133608
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 38
- Defined
- 125748
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.16 | 384 | 454 | 0.847 | 0.0000232 | 5696 |
| Missense (PolyPhen) | 83 | 119.03 | 0.69729 | 1517 | ||
| Synonymous | 0.721 | 148 | 160 | 0.927 | 0.00000778 | 1628 |
| Loss of Function | 3.80 | 24 | 54.1 | 0.443 | 0.00000318 | 657 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000093 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00024 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Putative regulatory subunit of serine/threonine-protein phosphatase 4.;
Recessive Scores
- pRec
- 0.0888
Intolerance Scores
- LoFtool
- 0.148
- RVIS EVS
- -1.09
- RVIS percentile EVS
- 7.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.755
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |