ASXL1

Additional sex combs like transcriptional regulator 1
Identifiers
Symbols	ASXL1 ; BOPS; MDS
External IDs	OMIM: 612990 MGI: 2684063 HomoloGene: 9098 GeneCards: ASXL1 Gene
Gene ontology Molecular function • DNA binding • transcription coactivator activity • transcription corepressor activity • protein binding • retinoic acid receptor binding • peroxisome proliferator activated receptor binding • metal ion binding Cellular component • nuclear chromatin • PR-DUB complex • extracellular exosome Biological process • negative regulation of transcription from RNA polymerase II promoter • heart morphogenesis • transcription, DNA-templated • response to retinoic acid • negative regulation of peroxisome proliferator activated receptor signaling pathway • monoubiquitinated histone H2A deubiquitination • negative regulation of fat cell differentiation • positive regulation of transcription from RNA polymerase II promoter • positive regulation of retinoic acid receptor signaling pathway • negative regulation of retinoic acid receptor signaling pathway • bone development • lung saccule development Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	171023	228790
Ensembl	ENSG00000171456	ENSMUSG00000042548
UniProt	Q8IXJ9	P59598
RefSeq (mRNA)	NM_001164603	NM_001039939
RefSeq (protein)	NP_001158075	NP_001035028
Location (UCSC)	Chr 20: 32.36 – 32.44 Mb	Chr 2: 153.35 – 153.4 Mb
PubMed search

Putative Polycomb group protein ASXL1 is a protein that in humans is encoded by the ASXL1 gene.^[1][2]

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. Although the function of the protein encoded by this gene is not known, it does show some sequence similarity to the protein encoded by the Drosophila Asx gene.^[2]

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[3]
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[4]
Citrobacter infection	Normal[5]
All tests and analysis from[6][7]

Model organisms have been used in the study of ASXL1 function. A conditional knockout mouse line, called Asxl1^{tm1a(EUCOMM)Wtsi[8][9]} 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.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] Twenty five tests were carried out on mutant mice and four significant abnormalities were observed.^[6] 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.^[6]

References

1. 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.
2. "Entrez Gene: ASXL1 additional sex combs like 1 (Drosophila)".
3. "Radiography data for Asxl1". Wellcome Trust Sanger Institute.
4. "Salmonella infection data for Asxl1". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Asxl1". Wellcome Trust Sanger Institute.
6. 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.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. 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.
11. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. 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.
13. 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.

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. 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. 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. 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. 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.