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MIM.601215 3q22-q24 HGNC:882

Thursday 1 November 2007

FRP1, FRAP-related protein 1; FRP1, SCKL, SCKL1, MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae) MIM.601215 3q22-q24

Ataxia telangiectasia and Rad3-related (ATR) protein is a kinase that regulates a DNA damage-response pathway.

ATR signaling is a pathway unusually sensitive to haploinsufficiency.

ATR (ataxia telangiectasia and Rad3 related) is an essential regulator of genome integrity.

ATR controls and coordinates DNA-replication origin firing, replication-fork stability, cell-cycle checkpoints, and DNA repair.


-  ATR is mutated in ATR-Seckel syndrome (ATR-SS), a disorder characterized by severe microcephaly and growth delay.

  • Impaired ATR signaling is also observed in cell lines from additional disorders characterized by microcephaly and growth delay, including non-ATR-SS, Nijmegen breakage syndrome, and MCPH1 (microcephaly, primary autosomal recessive, 1)-dependent primary microcephaly.

- Germline Mutation in ATR in Autosomal-Dominant Oropharyngeal Cancer Syndrome (22341969)


Phosphatidylinositol 3-kinase (PIK3) activity is implicated in diverse cellular responses triggered by mammalian cell surface receptors.

Members of the phosphatidylinositol kinase-related kinase (PIKK) family are high molecular mass kinases involved in cell cycle progression, DNA recombination, and the detection of DNA damage, as ATM or FRAP1.
The ATM protein is a member of the phosphatidylinositol-3 kinase (MIM.601232) family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell cycle control. The human ATM gene (MIM.607585) is defective in cells of patients with ataxia-telangiectasia (MIM.208900). ATM is involved in detection and response of cells to damaged DNA, is a member of this family.

Another member is FRAP1 (or mTOR) (MIM.601231), which is involved in a rapamycin-sensitive pathway leading to G1 cell cycle progression.


- Germline Mutation in ATR in Autosomal- Dominant Oropharyngeal Cancer Syndrome. Tanaka A, Weinel S, Nagy N, O’Driscoll M, Lai-Cheong JE, Kulp-Shorten CL, Knable A, Carpenter G, Fisher SA, Hiragun M, Yanase Y, Hide M, Callen J, McGrath JA. Am J Hum Genet. 2012 Feb 14. PMID: 22341969

- O’Driscoll M, Dobyns WB, van Hagen JM, Jeggo PA. Cellular and clinical impact of haploinsufficiency for genes involved in ATR signaling. Am J Hum Genet. 2007 Jul;81(1):77-86. PMID: 17564965