RARA (Retinoic acid receptor, alpha)

HGNC (Hugo)	RARA
LocusID (NCBI)	5914
Atlas_Id	46
Location	17q21.2  [Link to chromosome band 17q21]
Location_base_pair	Starts at 38465423 and ends at 38513895 bp from pter ( according to hg19-Feb_2009)  [Mapping RARA.png]
	c-RARA (17q21) in normal cells: PAC 833D9 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

Description	462 amino acids - 5 functional domains A/B (transcriptional regulation), C (DNA binding domain, contains 2 zinc fingers), D (cellular localization signal), E (ligand-binding domain) and F (function?)
Expression	in hematopoietic cells
Localisation	nuclear
Function	ligand-dependent transcription factor specifically involved in hematopoietic cells differentiation and maturation = receptor for all-trans retinoic acid (ATRA) and 9-cis RA which are intracellular metabolites of vitamine A, active in cellular differentiation and morphogenesis after linking with ATRA, RARA binds with a high affinity as a heterodimer with RXR (retinoid X receptor protein) to the RARE domain (retinoic acid response elements), a DNA sequence common to a number of genes and located in their promoter the gene response to RARA binding is modulated by a series of co-repressors and co-activators
Homology	with RARB and RARG (retinoic acid receptors ? and ?), 9-cis RA receptors (RXRs) and receptors for thyroid and steroid hormones and for vitamine D3

Implicated in

Note
Entity	t(15;17)(q24;q21) / acute promyelocytic leukemia (APL) -->PML - RARA
Disease	typical APL (or M3 AML, FAB classification), approximately 98% of APL cases; abnormal promyelocytes with Auer rods and bundles (faggots); disruption of the PODs with a microspeckeled pattern; maturation response to all-trans retinoic acid (ATRA) therapy
Prognosis	immediate prognosis impaired by intravascular disseminated coagulopathy; long term prognosis is favorable with treatment combining ATRA plus chemotherapy
Cytogenetics	variant or complex t(15;17) translocation in 5% of cases, no known prognosis implication; secondary chromosomal abnormalities in 30 to 35% of APL at diagnosis; association with +8 in 17 to 28% of cases; other associations are rare but recurrent: del(7q), del(9q), ider(17)t(15;17), +21
Hybrid/Mutated Gene	the crucial fusion transcript is 5'PML-3'RARA, encoded by der(15) chromosome; the counterpart 5'RARA-3'PML encoded by der(17) is inconstant breakpoint in RARA gene is always located in intron between A and B domains three breakpoint clusters in PML gene: bcr1 (70% of patients), bcr2 (10%) and bcr3 (20%), giving rise respectively to the long (L), intermediate (V) and short (S) length hybrid PML-RARAtranscripts; V form would be linked to ATRA decreased sensitivity and S form to association with an excess of secondary chromosome changes.
Abnormal Protein	106 Kda fusion protein; role in the leukemogenic process by probable interference with the signalling pathway leading to differentiation and maturation of myeloid precursors (mainly dysregulation of retinoid-inducible genes involved in myeloid differentiation)
Entity	t(11;17)(q23;q12) / acute promyelocytic leukemia -->PLZF-RARA
Disease	variant acute promyelocytic leukemia (APL) form with atypical cytologic aspects (intermediate morphology between M2 and M3, no Auer rods) and no response to ATRA therapy; less than 1% of APL cases.
Entity	t(5;17)(q35;q12) / acute promyelocytic leukemia --> NPM-RARA
Disease	exceptional; probable response to ATRA
Entity	t(11;17)(q13;q12) / acute promyelocytic leukemia --> NuMA-RARA
Disease	exceptional: probable response to ATRA
Entity	t(11;17)(q23;q12) / M5 acute non lymphocytic leukemia --> MLL-RARA
Disease	1 case to date; not to be confused with the t(11;17)(q23;q12) mentioned above; not found in APL; belongs to the MLL/11q23 leukemias

Breakpoints

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