PRRG2
protein-codingproline rich and Gla domain 2, the group of Proline rich and Gla domain containing
Gene summary
The protein encoded by this gene is a single-pass transmembrane protein containing an N-terminal gamma-carboxyglutamic acid (Gla) domain and tandem Pro/Leu-Pro-Xaa-Tyr (PY) motifs at its C-terminal end. The Gla domain is exposed on the cell surface while the PY motifs are cytoplasmic. The PY motifs of the encoded protein have been shown to interact with YAP1, a WW domain-containing protein. Therefore, it is thought that the encoded protein may be part of a signal transduction pathway. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.4 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 PRRG2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000951.3. 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 | 2 | 2 | ||||
| missense | 30 | 3 | 33 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 40 | 3 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000942.1 | 6 | MANE Select | |
| Ensembl | ENSP00000246794.4 | 6 | MANE Select | |
| RefSeq | NP_001303264.1 | 5 | Standard | |
| Ensembl | ENSP00000469258.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- calcium ion binding
- protein binding
Cellular Component
- extracellular region
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000246794
- Coding exons
- 6
- Length
- 10370
- Individuals with no LoFs
- 125559
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 189
- Defined
- 125748
- p
- 0.000752
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0886 | 110 | 107 | 1.02 | 0.00000565 | 1252 |
| Missense (PolyPhen) | 40 | 40.111 | 0.99722 | 469 | ||
| Synonymous | -0.454 | 46 | 42.2 | 1.09 | 0.00000183 | 432 |
| Loss of Function | 0.396 | 10 | 11.4 | 0.874 | 7.05e-7 | 116 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0085 | 0.0085 | notable |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00043 | 0.00038 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
Intolerance Scores
- LoFtool
- 0.406
- RVIS EVS
- 0.66
- RVIS percentile EVS
- 84.35
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.536
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |