PALB2

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Partner and localizer of BRCA2
PALB2 BRCA2.png
PyMOL rendered image based on 3EU7
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PALB2 ; FANCN; PNCA3
External IDs OMIM610355 MGI3040695 HomoloGene11652 GeneCards: PALB2 Gene
RNA expression pattern
PBB GE PALB2 219530 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 79728 233826
Ensembl ENSG00000083093 ENSMUSG00000044702
UniProt Q86YC2 Q3U0P1
RefSeq (mRNA) NM_024675 NM_001081238
RefSeq (protein) NP_078951 NP_001074707
Location (UCSC) Chr 16:
23.61 – 23.65 Mb
Chr 7:
122.11 – 122.13 Mb
PubMed search [1] [2]

Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.[1][2][3]

Function[edit]

Characterized domaines of PALB2

This gene encodes a protein that functions in genome maintenance (double strand break repair). This protein binds to and colocalizes with the breast cancer 2 early onset protein (BRCA2) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2.[1] PALB2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulates strand invasion a vital step of homologous recombination.[4] PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.[4]

Clinical significance[edit]

Variants in the PALB2 gene are associated with an increased risk of developing breast cancer [5] of magnitude similar to that associated with BRCA2 mutations [6] and PALB2-deficient cells are sensitive to PARP inhibitors. [4]

PALB2 was recently identified as a susceptibility gene for familial pancreatic cancer by scientists at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins. This has paved for the way for developing a new gene test for families where pancreatic cancer occurs in multiple family members.[7] Tests for PALB2 have been developed by Ambry Genetics [8]and Myriad Genetics[9] that are now available.

Biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia.[3]

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: PALB2 partner and localizer of BRCA2". 
  2. ^ Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM (June 2006). "Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2". Mol. Cell 22 (6): 719–29. doi:10.1016/j.molcel.2006.05.022. PMID 16793542. 
  3. ^ a b Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP (February 2007). "Fanconi anemia is associated with a defect in the BRCA2 partner PALB2". Nat. Genet. 39 (2): 159–61. doi:10.1038/ng1942. PMID 17200672. 
  4. ^ a b c Buisson R, Dion-Côté AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, Stasiak A, Xia B, Masson JY (2010). "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.". Nature Structural & molecular biology 17 (10): 1247–54. doi:10.1038/nsmb.1915. PMID 20871615. 
  5. ^ Chen P, Liang J, Wang Z, Zhou X, Chen L, Li M, Xie D, Hu Z, Shen H, Wang H (September 2008). "Association of common PALB2 polymorphisms with breast cancer risk: a case-control study". Clin. Cancer Res. 14 (18): 5931–7. doi:10.1158/1078-0432.CCR-08-0429. PMID 18794107. 
  6. ^ Antoniou A et al (August 7 2014). "Breast-Cancer Risk in Families with Mutations in PALB2". N Engl J Med 2014 371: 497–506. doi:10.1056/NEJMoa1400382. 
  7. ^ Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP (2009). "Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene.". Science 324 (5924): 217. doi:10.1126/science.1171202. PMC 2684332. PMID 19264984. 
  8. ^ "Ambry Genetics". 
  9. ^ "Myriad Genetics". 

Further reading[edit]