ASXL1

ASXL1
Identifiers
Aliases	ASXL1 , BOPS, MDS, additional sex combs like 1, transcriptional regulator, ASXL transcriptional regulator 1
External IDs	OMIM: 612990 MGI: 2684063 HomoloGene: 9098 GeneCards: ASXL1
Gene location (Human) Chr. Chromosome 20 (human) [1] Band 20q11.21 Start 32,358,330 bp [1] End 32,439,319 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 H1 Start 153,187,749 bp [2] End 153,245,927 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve sperm gastric mucosa body of pancreas oocyte left lobe of thyroid gland nipple right lung right lobe of thyroid gland upper lobe of left lung Top expressed in primitive streak renal corpuscle condyle medullary collecting duct secondary oocyte fossa spermatid substantia nigra motor neuron external carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding metal ion binding protein binding peroxisome proliferator activated receptor binding transcription coactivator activity retinoic acid receptor binding chromatin binding Cellular component PR-DUB complex nucleus nucleoplasm Biological process regulation of transcription, DNA-templated heart morphogenesis monoubiquitinated histone H2A deubiquitination transcription, DNA-templated lung saccule development bone development negative regulation of fat cell differentiation positive regulation of retinoic acid receptor signaling pathway negative regulation of peroxisome proliferator activated receptor signaling pathway positive regulation of transcription by RNA polymerase II response to retinoic acid cell morphogenesis animal organ morphogenesis protein deubiquitination hematopoietic or lymphoid organ development thymus development bone marrow development homeostasis of number of cells chromatin organization hemopoiesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 171023 228790 Ensembl ENSG00000171456 ENSMUSG00000042548 UniProt Q8IXJ9 P59598 RefSeq (mRNA) NM_001164603 NM_015338 NM_001363734 NM_001039939 RefSeq (protein) NP_001158075 NP_056153 NP_001350663 NP_001158075.1 NP_001035028 Location (UCSC) Chr 20: 32.36 – 32.44 Mb Chr 2: 153.19 – 153.25 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Putative Polycomb group protein ASXL1 is a protein that in humans is encoded by the ASXL1 gene. ^{[5] [6]}

In Drosophila , the Additional sex combs (Asx) gene encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. ^[6]

Model organisms

Asxl1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Abnormal [7]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
MicroCT & Quantitative Faxitron	Abnormal
Salmonella infection	Normal [8]
Citrobacter infection	Normal [9]
All tests and analysis from [10] [11]

Model organisms have been used in the study of ASXL1 function. A conditional knockout mouse line, called Asxl1^{tm1a(EUCOMM)Wtsi [12] [13]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. ^{[14] [15] [16]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[10] [17]} Twenty five tests were carried out on mutant mice and four significant abnormalities were observed. ^[10] Few homozygous mutant embryos were identified during gestation and those that were alive had craniofacial and eye defects, none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; decreased vertebrae number and increased bone strength was observed in these animals. ^[10]

See also

• ASXL2
• ASXL3

References

1. GRCh38: Ensembl release 89: ENSG00000171456 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042548 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Fisher CL, Berger J, Randazzo F, Brock HW (Mar 2003). "A human homolog of Additional sex combs, ADDITIONAL SEX COMBS-LIKE 1, maps to chromosome 20q11". Gene. 306: 115–26. doi:10.1016/S0378-1119(03)00430-X. PMID   12657473.
6. "ASXL1 ASXL transcriptional regulator 1 [ Homo sapiens (human) ]".
7. "Radiography data for Asxl1". Wellcome Trust Sanger Institute.
8. "Salmonella infection data for Asxl1". Wellcome Trust Sanger Institute.
9. "Citrobacter infection data for Asxl1". Wellcome Trust Sanger Institute.
10. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
11. Mouse Resources Portal, Wellcome Trust Sanger Institute.
12. "International Knockout Mouse Consortium".
13. "Mouse Genome Informatics".
14. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
15. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
16. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
17. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi: 10.1186/gb-2011-12-6-224 . PMC   3218837 . PMID   21722353.

External links

• Human ASXL1 genome location and ASXL1 gene details page in the UCSC Genome Browser .

Further reading

• Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi: 10.1093/dnares/9.3.99 . PMID   12168954.
• Sinclair DA, Campbell RB, Nicholls F, et al. (1992). "Genetic Analysis of the Additional Sex Combs Locus of Drosophila Melanogaster". Genetics. 130 (4): 817–25. doi:10.1093/genetics/130.4.817. PMC   1204931 . PMID   1349871.
• Sinclair DA, Milne TA, Hodgson JW, et al. (1998). "The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes". Development. 125 (7): 1207–16. doi:10.1242/dev.125.7.1207. PMID   9477319.
• Nagase T, Ishikawa K, Suyama M, et al. (1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. doi: 10.1093/dnares/6.1.63 . PMID   10231032.
• Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi: 10.1038/414865a . PMID   11780052.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.