PPP1R13L (protein phosphatase 1, regulatory (inhibitor) subunit 13 like)
2006-12-01 Ulla Vogel AffiliationNational Research Centre for the Working Environment, Lersø Parkalle 105, DK-2100 Copenhagen O, Denmark
Identity
HGNC
LOCATION
19q13.32
LOCUSID
ALIAS
IASPP,NKIP1,RAI,RAI4
FUSION GENES
DNA/RNA
Description
26,674 bp 13 exons.
Transcription
3,076 bps.
Proteins
Description
828 amino acids.
Function
PPP1R13L was originally named RAI, an acronym for RelA associated inhibitor. It was originally identified by yeast two-hybrid screening using RelA as bait. PPP1R13L was shown to associate specifically with relA and inhibit relA mediated NF-kappaB activated transcription when NF-kappaB specific transcription was activated by TNF. Yang et al. found no interaction with p53. The mRNA expression was examined in several tissues and was found to be high in heart, placenta, prostate tissues and detectable in lung, kidney, pancreas, spleen thymus, ovary, small intestine and colon. Bergamaschi et al found that PPP1R13L interacts with p53. Antisense RNA or RNAi mediated down regulation of PPP1R13L expression and induced apoptosis. Increased expression of PPP1R13L lead to increased resistance towards cisplatin and UV-induced apoptosis. This indicates that RAI inhibits apoptosis.
Several studies provide evidence that PPP1R13L expression is increased in tumor tissue. In a study of colorectal adenomas and colorectal cancers, PPP1R13L expression was found to be substantially higher in lesions than in the normal tissue from the same patient. PPP1R13L expression has also been found to be increased in breast carcinomas and in blood cells in patients with acute leukemia.
In a prospective study of lung cancer among 265 lung cancer cases and 272 controls nested within the population based Diet, Cancer and Health study, PPP1R13L expression in mononuclear blood cells (isolated by buffy coat) was not associated with risk of lung cancer. mRNA levels were found to be 41% higher in women than in men.
Several studies provide evidence that PPP1R13L expression is increased in tumor tissue. In a study of colorectal adenomas and colorectal cancers, PPP1R13L expression was found to be substantially higher in lesions than in the normal tissue from the same patient. PPP1R13L expression has also been found to be increased in breast carcinomas and in blood cells in patients with acute leukemia.
In a prospective study of lung cancer among 265 lung cancer cases and 272 controls nested within the population based Diet, Cancer and Health study, PPP1R13L expression in mononuclear blood cells (isolated by buffy coat) was not associated with risk of lung cancer. mRNA levels were found to be 41% higher in women than in men.
Mutations
Note
Genetic Epidemiology:
The most frequently studied polymorphism in PPP1R13L is PPP1R13L IVS1 A4364G (rs1970764). Carriers of the variant allele have been shown to be at decreased risk of basal cell carcinoma among younger persons (< 50 years), breast cancer (60 years).
These results indicate that the haplotype may be associated with risk of cancer primarily among young and middle aged persons and that it may be specific for women.
The most frequently studied polymorphism in PPP1R13L is PPP1R13L IVS1 A4364G (rs1970764). Carriers of the variant allele have been shown to be at decreased risk of basal cell carcinoma among younger persons (< 50 years), breast cancer (60 years).
These results indicate that the haplotype may be associated with risk of cancer primarily among young and middle aged persons and that it may be specific for women.
Implicated in
Entity name
General increased cancer risk
Note
No human disease has been linked to inactivation of PPP1R13L. However, polymorphisms in PPP1R13L may be associated with increased cancer risk (see above).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12524540 | 2003 | iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. | Bergamaschi D et al |
| 15885892 | 2005 | Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer. | Laska MJ et al |
| 16824210 | 2006 | Clinical management of women with metastatic breast cancer: a descriptive study according to age group. | Manders K et al |
| 12771034 | 2003 | A specific haplotype of single nucleotide polymorphisms on chromosome 19q13.2-3 encompassing the gene RAI is indicative of post-menopausal breast cancer before age 55. | Nexø BA et al |
| 14757194 | 2004 | Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer. | Vogel U et al |
| 16054657 | 2006 | ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of Danes. | Vogel U et al |
| 15936590 | 2005 | Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50. | Vogel U et al |
| 16690207 | 2007 | Gene-environment interactions between smoking and a haplotype of RAI, ASE-1 and ERCC1 polymorphisms among women in relation to risk of lung cancer in a population-based study. | Vogel U et al |
| 10336463 | 1999 | Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. | Yang JP et al |
| 12433725 | 2002 | Multiple single nucleotide polymorphisms on human chromosome 19q13.2-3 associate with risk of Basal cell carcinoma. | Yin J et al |
| 15607367 | 2005 | The expression of iASPP in acute leukemias. | Zhang X et al |
Other Information
Locus ID:
NCBI: 10848
MIM: 607463
HGNC: 18838
Ensembl: ENSG00000104881
Variants:
dbSNP: 10848
ClinVar: 10848
TCGA: ENSG00000104881
COSMIC: PPP1R13L
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA164713176 | Platinum compounds | Chemical | ClinicalAnnotation | associated | PD | 19203783 | |
| PA444937 | Mesothelioma | Disease | ClinicalAnnotation | associated | PD | ||
| PA445204 | Ovarian Neoplasms | Disease | ClinicalAnnotation | associated | PD | 19203783 | |
| PA449014 | cisplatin | Chemical | ClinicalAnnotation | associated | PD | ||
| PA449748 | gemcitabine | Chemical | ClinicalAnnotation | associated | PD |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37698259 | 2024 | Variable phenotype of a null PPP1R13L allele in children with dilated cardiomyopathy. | 0 |
| 37698259 | 2024 | Variable phenotype of a null PPP1R13L allele in children with dilated cardiomyopathy. | 0 |
| 37147350 | 2023 | Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese. | 3 |
| 37147350 | 2023 | Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese. | 3 |
| 35121659 | 2022 | iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca(2+) homeostasis and control tumor growth and drug resistance. | 3 |
| 35169254 | 2022 | iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation. | 5 |
| 35351459 | 2022 | TP53 common variants and interaction with PPP1R13L and CD3EAP SNPs and lung cancer risk and smoking behavior in a Chinese population. | 3 |
| 35717675 | 2022 | Chitosan-Gelatin-EGCG Nanoparticle-Meditated LncRNA TMEM44-AS1 Silencing to Activate the P53 Signaling Pathway for the Synergistic Reversal of 5-FU Resistance in Gastric Cancer. | 24 |
| 35121659 | 2022 | iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca(2+) homeostasis and control tumor growth and drug resistance. | 3 |
| 35169254 | 2022 | iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation. | 5 |
| 35351459 | 2022 | TP53 common variants and interaction with PPP1R13L and CD3EAP SNPs and lung cancer risk and smoking behavior in a Chinese population. | 3 |
| 35717675 | 2022 | Chitosan-Gelatin-EGCG Nanoparticle-Meditated LncRNA TMEM44-AS1 Silencing to Activate the P53 Signaling Pathway for the Synergistic Reversal of 5-FU Resistance in Gastric Cancer. | 24 |
| 34705028 | 2021 | iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning. | 6 |
| 34705028 | 2021 | iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning. | 6 |
| 32005663 | 2020 | A previously identified apoptosis inhibitor iASPP confers resistance to chemotherapeutic drugs by suppressing senescence in cancer cells. | 8 |
Citation
Ulla Vogel
PPP1R13L (protein phosphatase 1, regulatory (inhibitor) subunit 13 like)
Atlas Genet Cytogenet Oncol Haematol. 2006-12-01
Online version: http://atlasgeneticsoncology.org/gene/42997/ppp1r13l
