The reference OMIM entry for this protein is 601489

Insulin-like growth factor-binding protein, acid-labile subunit; igfals
Igfbp, soluble
Acid-labile subunit; als

DESCRIPTION

In vivo, insulin-like growth factors I (IGF1; 147440) and II (IGF2; 147470) are always complexed to one of a family of 6 IGF-binding proteins, IGFBP1 (146730), IGFBP2 (146731), IGFBP3 (146732), IGFBP4 (146733), IGFBP5 (146734), and IGFBP6 (146735). Until birth, binary IGFBP/IGF complexes of 50 kD predominate in serum, with IGFBP2 being the most frequently occurring IGFBP moiety. In juvenile and adult mammals, however, 80 to 85% of serum IGFs are found in a ternary complex of 150 kD composed of 1 molecule each of IGF, IGFBP3, and a protein that is found only in serum, the acid-labile subunit (ALS). ALS migrates at an apparent molecular mass of 84 to 86 kD. ALS retains the IGFBP3/IGF complexes in the vascular compartment and extends the half-life of IGFs in the circulation. Synthesis of ALS occurs mainly in liver after birth and is stimulated by growth hormone (139250) (summary by Boisclair et al., 1996).

CLONING

Dai and Baxter (1992) and Baxter and Dai (1994) studied the acid-labile subunit of the rat IGF binding protein complex. Boisclair et al. (1996) cloned and characterized the mouse Igfals gene. Leong et al. (1992) isolated full-length clones encoding the acid-labile subunit of the IGF binding protein complex from human liver cDNA libraries by using probes based on amino acid sequence data from the purified protein. These clones encode a mature protein of 578 amino acids preceded by a 27-amino acid hydrophobic sequence indicative of a secretion signal. Expression of the cDNA clones in mammalian tissue culture cells resulted in the secretion into the culture media of ALS activity that could form the expected complex with IGF1 and IGFBP3. The amino acid sequence of ALS is largely composed of 18 to 20 leucine-rich repeats of 24 amino acids. These repeats are found in a number of diverse proteins that, like ALS, participate in protein-protein interactions.

GENE STRUCTURE

Boisclair et al. (1996) found that the mouse Igfals gene contains 2 exons. Domene et al. (2004) stated that the human IGFALS gene contains 2 exons.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the IGFALS gene to chromosome 16 (TMAP WI-7742). Domene et al. (2011) stated that the IGFALS gene maps to chromosome 16p13.3. Boisclair et al. (1996) mapped the mouse Igfals gene to chromosome 17 by fluorescence in situ hybridization.

MOLECULAR GENETICS

In a 17-year-old boy with acid-labile subunit deficiency (ACLSD; 615961) who had delayed onset of puberty, slow pubertal progress, and only minimal slowing of linear growth, Domene et al. (2004) identified a homozygous inactivating mutation in the IGFALS gene (601489.0001). In 3 sibs with acid-labile subunit deficiency, Domene et al. (2007) identified compound heterozygous mutations in the IGFALS gene (601489.0002-601489.0003). Domene et al. (2011) stated that 16 unique homozygous or compound heterozygous inactivating mutations of the IGFALS gene had been identified in 21 patients with acid-labile subunit deficiency from 16 different families of various ethnic backgrounds. All of the mutations occurred in exon 2 and included missense mutations, frameshifts with a premature stop codon, in-frame insertions, and nonsense mutations. Thirteen of the mutations produced defects in the leucine-rich repeat region of the protein.

ANIMAL MODEL

To evaluate the importance of IGFALS and ternary complexes, Ueki et al. (2000) generated mice in whi ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 601489 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).