HGNC Approved Gene Symbol: FIBP
SNOMEDCT: 1169359006;
Cytogenetic location: 11q13.1 Genomic coordinates (GRCh38): 11:65,883,740-65,888,471 (from NCBI)
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
---|---|---|---|---|
11q13.1 | Thauvin-Robinet-Faivre syndrome | 617107 | Autosomal recessive | 3 |
Using the yeast 2-hybrid system, Kolpakova et al. (1998) identified a HeLa cell cDNA, which the authors termed FIBP, that interacts with acidic fibroblast growth factor (FGF1; 131220). The FIBP cDNA encodes a deduced 372-amino acid protein with a predicted molecular mass of 42 kD. The protein is mainly hydrophilic and has no N-terminal signal sequence. Northern blot analysis demonstrated that FIBP and FGF1 have similar expression patterns. FIBP is expressed ubiquitously as an approximately 1.4-kb transcript at highest levels in heart, skeletal muscle, and pancreas, and at somewhat lower levels in brain. In vitro experiments showed that FIBP readily attaches to microsomal membranes and is capable of binding FGF1 with high affinity. Immunofluorescence studies demonstrated that FIBP is mainly localized in the nucleus and to a lesser extent in mitochondria and other cytoplasmic membranes. Western blot analysis indicated the presence of 2 forms of FIBP.
By RT-PCR analysis, Kolpakova et al. (2000) identified a second FIBP transcript caused by alternative splicing of exon 5 and resulting in a protein with an additional 7 residues. They cloned and characterized the mouse Fibp gene and, by database searching, identified a Drosophila homolog. Human FIBP shares 97% and 46% sequence identity with the mouse and Drosophila homologs, respectively.
Akawi et al. (2016) found expression of the Fibp gene in mouse embryos. A uniform weak signal was observed throughout the embryo at day E10.5. It was expressed in all regions of the central nervous system at day E12.5, with high expression in the dorsal mid- and forebrain, the ventral part of caudal diencephalon, and in dorsal root ganglia. Expression was also detected in the kidneys and lungs, but not in the heart.
Kolpakova et al. (2000) determined that the FIBP gene contains 10 exons and spans more than 5 kb. Sequence analysis of the region surrounding the translation start revealed a CpG island. Functional studies of the promoter region suggested strong transcriptional activity.
By FISH, Kolpakova et al. (2000) mapped the FIBP gene to chromosome 11q13.1.
In a 23-year-old man, born of consanguineous North African parents, with Thauvin-Robinet-Faivre syndrome (TROFAS; 617107), Thauvin-Robinet et al. (2016) identified a homozygous nonsense mutation in the FIBP gene (Q218X; 608296.0001). The mutation, which was found by exome sequencing, segregated with the disorder in the family. Patient fibroblasts showed excessive proliferation compared to controls.
In 3 sibs, born of consanguineous Arab parents, with TROFAS, Akawi et al. (2016) identified a homozygous mutation in the FIBP gene (608296.0002). Patient fibroblasts showed increased cellular proliferation compared to controls.
In a 23-year-old man, born of consanguineous North African parents, with Thauvin-Robinet-Faivre syndrome (TROFAS; 617107), Thauvin-Robinet et al. (2016) identified a homozygous c.652C-T transition (chr11.65,652,652G-A, GRCh37) in the FIBP gene, resulting in a gln218-to-ter (Q218X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was filtered against the dbSNP (build 135) and Exome Sequencing Project databases, as well as 260 in-house exomes. The mutation segregated with the disorder in the family. Patient cells showed significantly decreased levels of FIBP transcript compared to controls, suggesting nonsense-mediated mRNA decay. Patient fibroblasts showed excessive proliferation compared to controls.
In 3 sibs, born of consanguineous Arab parents, with Thauvin-Robinet-Faivre syndrome (TROFAS; 617107), Akawi et al. (2016) identified a homozygous in-frame 3-bp insertion (c.175_176insTAA, NM_198897.1) in the FIBP gene, resulting in an indel (His59delinsLeuAsn). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, was confirmed by Sanger sequencing. The mutation segregated with the disorder in the family and was not found in public databases or in in-house control exomes. Patient fibroblasts showed increased cellular proliferation compared to controls.
Akawi, N., Ben-Salem, S., Lahti, L., Partanen, J., Ali, B. R., Al-Gazali, L. A recessive syndrome of intellectual disability, moderate overgrowth, and renal dysplasia predisposing to Wilms tumor is caused by a mutation in FIBP gene. Am. J. Med. Genet. 170A: 2111-2118, 2016. [PubMed: 27183861] [Full Text: https://doi.org/10.1002/ajmg.a.37741]
Kolpakova, E., Frengen, E., Stokke, T., Olsnes, S. Organization, chromosomal localization and promoter analysis of the gene encoding human acidic fibroblast growth factor intracellular binding protein. Biochem. J. 352: 629-635, 2000. [PubMed: 11104667]
Kolpakova, E., Wiedlocha, A., Stenmark, H., Klingenberg, O., Falnes, P. O., Olsnes, S. Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor. Biochem. J. 336: 213-222, 1998. [PubMed: 9806903] [Full Text: https://doi.org/10.1042/bj3360213]
Thauvin-Robinet, C., Duplomb-Jego, L., Limoge, F., Picot, D., Masurel, A., Terriat, B., Champilou, C., Minot, D., St-Onge, J., Kuentz, P., Duffourd, Y., Thevenon, J., Riviere, J.-B., Faivre, L. Homozygous FIBP nonsense variant responsible of (sic) syndromic overgrowth, with overgrowth, macrocephaly, retinal coloboma and learning disabilities. Clin. Genet. 89: e1-4, 2016. Note: Electronic Article. [PubMed: 26660953] [Full Text: https://doi.org/10.1111/cge.12704]