2 exons spanning 2824bp although only exon1 codes for the protein. Orientation + strand. Exon 1 101875594-101876910 (1317 bp), Exon 2 101877270-101878417 (1148 bp), Intron 1-2 101876911-101877269 (359 bp). Gene id= 429 (KEGG). Refseq: NM_004316.2
HASH1/ASCL1 promoter has two independent transcription start sites of which proximal INR element (YYANYY consensus binding site) plays a predominant role. The general enhancer has several Sp1 binding sites. Tissue restricted expression control comes from the repressor regions present in the distal (over 13.5kb upstream) and proximal 5 flanking region. The proximal repressor is shown to have a class C element site to which HES1 can bind and regulate HASH1/ASCL1 expression.
Variant: 158--158 Glu to Gly (E to G) Var_013179 in P50553

2.46 Kb mRNA, coding sequence 711 bp

This gene encodes a member of the basic helix-loop-helix (bHLH) family of transcription factors. The protein activates transcription by binding to the E box (5-CANNTG-3). Dimerization with other bHLH proteins is required for efficient DNA binding. This protein plays a role in the neuronal commitment and differentiation and in the generation of olfactory and autonomic neurons. It is highly expressed in medullary thyroid cancer (MTC) and small cell lung cancer (SCLC) and may be a useful marker for these cancers. The proximal coding region of the cDNA contains a striking 14-copy repeat of the triplet CAG that exhibits polymorphism in human genomic DNA The presence of a CAG repeat in the gene suggests that it could play a role in tumor formation.
Protein size: 237 aa, 25.45kDa. Refseq: NP_004307.2

The amino terminal of the protein contains poly alanine and poly glutamine repeat rich region. The polyglutamine length polymorphism in ASCL1 has been postulated that it could influence predispositions to Parkinsons disease. The carboxy terminus of the protein contains the basic helix loop helix domain, which is important for interaction with other transcription factors.

The gene product is expressed basically nuclear and is expressed in tissues like brain, lung and nervous system.

ASCL1 functions as a bHLH transcription factor that binds to E-box whose canonical sequence is 5CANNTG 3. It also acts as protein binding, transcription factor, and in cell differentiation. MASH1/ASCL1 is expressed during development of rat retina and interacts specifically with an E-box identified in the promoter for the opsin gene during rod photoreceptor differentiation. NOTCH1 and its downstream signal transducer HES1 regulates the transcription of HASH1/ASCL1 and is very instrumental in neuronal developmental pathways particularly dictating neuroendocrine differentiation in various organs.
Interacting partners: E1A binding protein p300, Ubiquilin 1, Bone morphogenetic protein 2 (BMP2), Trancription factor 3 (TF3), Transcription factor 4 (TF4), Myocyte specific Enhancer factor 2A (MSEF2A), Neurogenin.

Mus musculus Ascl1 achaete-scute complex homolog-like 1 (Drosophila) NM_008553.2; Rattus norvegicus Ascl1 achaete-scute complex homolog-like 1 (Drosophila) NM_022384.1; Canis familiaris similar to achaete-scute homolog 1 LOC482628; Danio Rerio achaete scute homolog A asha NM_131219.1.

Congenital central hypoventilation syndrome is a rare disorder of the chemical control of breathing. The ASCL1--PHOX2A--PHOX2B developmental cascade was proposed as a candidate pathway for this disorder, as well as for Haddad syndrome, because the cascade controls the development of neurons with a definitive or transient noradrenergic phenotype. De Pontual et al. identified heterozygosity for mutations in the ASCL1 gene in 2 patients with CCHS and 1 patient with Haddad syndrome. The authors also developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest. All Ascl1 mutant alleles result in impaired noradrenergic neuronal development when over expressed from adenoviral constructs.
ALLELIC VARIANTS
1. ASCL1 C52A, PRO18THR
In a patient with CCHS, de Pontual et al identified heterozygosity for a 52C-A transversion in the ASCL1 gene, translating in a pro18-to-thr substitution. The patient was also heterozygous for a polyalanine expansion mutation in PHOX2B, which is known to induce CCHS.
2. ASCL1, 15-BP DEL, NT111
Heterozygosity for a 15-bp deletin (111-115 Del 15nt) in the ASCL1 gene was reported in a patient with CCHS by de Pontual et al. The mutation was predicted to result in loss of 5 of 13 alanine residues (ala37-ala41) in a polyalanine tract.
3. ASCL1, 24-BP DEL, NT108
Another heterozygosity for of 24-bp deletion (108-131del24nt) in the ASCL1 gene was identified in a patient with Haddad syndrome (209880), de Pontual et al The mutation was predicted to result in loss of 8 of 13 alanine residues (ala36-ala43) in a polyalanine tract.
Genetic association with Parkinsons disease has been shown by Ide M et al (PMID=16021468) and that with sudden infant death syndrome or (SIDS) has been shown by Weese-Mayer DE et al (PMID= 15240857)