Alternative titles; symbols
HGNC Approved Gene Symbol: FGF6
Cytogenetic location: 12p13.32 Genomic coordinates (GRCh38): 12:4,434,142-4,445,815 (from NCBI)
By screening a mouse cosmid library with a human HST (FGF4; 164980) probe under reduced conditions of stringency, Marics et al. (1989) isolated several positive clones, one of which was identified as a new member of the fibroblast growth factor gene family. They subsequently isolated and sequenced the gene, which they called FGF6. The deduced amino acid sequence showed 70% identity with the HST gene product over the C-terminal two-thirds of the putative protein. FGF6 is the same as the HST2 oncogene, which was identified by its close homology to the HST1 gene.
Iida et al. (1992) determined that the HST2 gene encodes a 198-amino acid protein containing a signal peptide with the characteristics of a heparin-binding growth factor. RNA blot analysis detected expression of HST2 in human leukemia cell lines with platelet/megakaryocytic differentiation potential.
Fiore et al. (2000) stated that expression of FGF6 is essentially restricted to developing and adult skeletal muscle.
Marics et al. (1989) showed that the cloned normal FGF6 gene transformed mouse NIH 3T3 fibroblasts using both focus and tumorigenicity assays.
Guo et al. (2019) used a diagnostic code-based phenotype algorithm in a homogeneous population to identify 18 cases of hemochromatosis and 6,896 controls. A gene-based compound heterozygosity scan for putative functional alleles identified 2 genes, HFE (613609) and FGF6, that showed exomewide-significant association with iron overload. Protein-protein interaction network inference found evidence that FGF6 is involved in the iron metabolism network, and functional experiments demonstrated that FGF6 regulates iron homeostasis and induces transcriptional regulation of hepcidin antimicrobial peptide (HAMP; 606464). Three FGF6 variants were identified that caused significant downregulation of HAMP mRNA in transfection studies in several cell types. The induction of hepcidin expression by FGF6 leads to degradation of ferroportin (SLC40A1; 604653) through binding and internalization of ferroportin by hepcidin.
Marics et al. (1989) mapped FGF6 to 12p13 by in situ hybridization. The mapping of HST2 to 12p13 and of HST1 to 11q13 is further evidence of the homeology between these 2 human chromosomes. Studying 2 somatic cell hybrids containing either the der(12) or the der(X) from a mesothelioma with a translocation t(X;12)(q22;p13) as the only chromosomal change, Aerssens et al. (1994) demonstrated that FGF6 lies distal to the 12p13 breakpoint and to VWF (613160).
Fiore et al. (2000) found that Fgf6-null mice showed normal muscle regeneration following chemical or crush injury. They concluded that FGF6 is either not involved in muscle regeneration or that this role is strictly compensated by other factors.
Neuhaus et al. (2003) stated that regeneration of skeletal muscles in Fgf6 and Fgf6/mdx (see DMD, 300377) mutant mice was impaired. They found that the combined loss of Fgf2 (134920) and Fgf6 led to severe dystrophic changes in the musculature of mdx mice, with reduced formation of new myotubes in regenerating muscle; there was no significant reduction in the number of skeletal muscle satellite cells. Fgf6 mutant myoblasts showed decreased migration ability when transplanted into wildtype mice.
Aerssens, J., Chaffanet, M., Baens, M., Matthijs, G., Van Den Berghe, H., Cassiman, J.-J., Marynen, P. Regional assignment of seven loci to 12p13.2-pter by PCR analysis of somatic cell hybrids containing the der(12) or the der(X) chromosome from a mesothelioma showing t(X;12)(q22;p13). Genomics 20: 119-121, 1994. [PubMed: 8020938] [Full Text: https://doi.org/10.1006/geno.1994.1136]
Fiore, F., Sebille, A., Birnbaum, D. Skeletal muscle regeneration is not impaired in Fgf6 -/- mutant mice. Biochem. Biophys. Res. Commun. 272: 138-143, 2000. [PubMed: 10872817] [Full Text: https://doi.org/10.1006/bbrc.2000.2703]
Guo, S., Jiang, S., Epperla, N., Ma, Y., Maadooliat, M., Ye, Z., Olson, B., Wang, M., Kitchner, T., Joyce, J., An, P., Wang, F., Strenn, R., Mazza, J. J., Meece, J. K., Wu, W., Jin, L., Smith, J. A., Wang, J., Schrodi, S. J. A gene-based recessive diplotype exome scan discovers FGF6, a novel hepcidin-regulating iron-metabolism gene. Blood 133: 1888-1898, 2019. [PubMed: 30814063] [Full Text: https://doi.org/10.1182/blood-2018-10-879585]
Iida, S., Yoshida, T., Naito, K., Sakamoto, H., Katoh, O., Hirohashi, S., Sato, T., Onda, M., Sugimura, T., Terada, M. Human hst-2 (FGF-6) oncogene: cDNA cloning and characterization. Oncogene 7: 303-309, 1992. [PubMed: 1549352]
Marics, I., Adelaide, J., Raybaud, F., Mattei, M.-G., Coulier, F., Planche, J., de Lapeyriere, O., Birnbaum, D. Characterization of the HST-related FGF.6 gene, a new member of the fibroblast growth factor gene family. Oncogene 4: 335-340, 1989. [PubMed: 2649847]
Neuhaus, P., Oustanina, S., Loch, T., Kruger, M., Bober, E., Dono, R., Zeller, R., Braun, T. Reduced mobility of fibroblast growth factor (FGF)-deficient myoblasts might contribute to dystrophic changes in the musculature of FGF2/FGF6/mdx triple-mutant mice. Molec. Cell. Biol. 23: 6037-6048, 2003. [PubMed: 12917328] [Full Text: https://doi.org/10.1128/MCB.23.17.6037-6048.2003]