Alternative titles; symbols
HGNC Approved Gene Symbol: HHIPL2
Cytogenetic location: 1q41 Genomic coordinates (GRCh38): 1:222,522,264-222,548,104 (from NCBI)
HHIPL2 encodes an inhibitor of the Hedgehog (see 600725) signaling pathway whose expression is reduced in the presence of iron (Doyard et al., 2012).
By bioinformatic analysis, Katoh and Katoh (2006) identified HHIPL2 gene as a member of the HHIP gene family. The HHIPL2 protein contains 724, 717, and 712 amino acids in human, mouse, and rat, respectively. HHIPL2 has an HHIP homologous (HIPH) domain with 18 conserved cys residues and is a type II transmembrane protein with a short N-terminal cytoplasmic region. In silico analysis showed HHIPL2 mRNA expression in testis, thyroid gland, osteoarthritic cartilage, pancreatic cancer, and lung cancer.
By microarray analysis, Doyard et al. (2012) showed that iron decreased expression of HHIPL2 in MG63 osteoblast cells. Quantitative RT-PCR analysis confirmed the results and demonstrated that modulation of HHIPL2 expression by iron was dose dependent. Knockdown of HHIPL2 expression in MG63 cells decreased the transcript levels of osteoblast markers, consistent with HHIPL2's role in modulating hedgehog (see 600725) transduction signal pathway activity
Katoh and Katoh (2006) stated that the HHIPL2 gene maps to chromosome 1q41.
Doyard, M., Fatih, N., Monnier, A., Island, M. L., Aubry, M., Leroyer, P., Bouvet, R., Chales, G., Mosser, J., Loreal, O., Guggenbuhl, P. Iron excess limits HHIPL-2 gene expression and decreases osteoblastic activity in human MG-63 cells. Osteoporos. Int. 23: 2435-2445, 2012. [PubMed: 22237814] [Full Text: https://doi.org/10.1007/s00198-011-1871-z]
Katoh, Y., Katoh, M. Comparative genomics on HHIP family orthologs. Int. J. Molec. Med. 17: 391-395, 2006. [PubMed: 16391842]