• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
FGF10 (HGNC:3666) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
fibroblast growth factor 10
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
0.55(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.94(Read more about gnomAD pLI score)
LOEUF
0.34(Read more about gnomAD LOEUF score)
Cytoband
5p12
Genomic Coordinates
GRCh37/hg19: chr5:44300349-44389522 NCBI Ensembl UCSC
GRCh38/hg38: chr5:44300247-44389420 NCBI Ensembl UCSC
MANE Select Transcript
NM_004465.2 ENST00000264664.5 (Read more about MANE Select)
Function
Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. May play a role in wound healing. {ECO:0000269|PubMed:16597617}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-24999
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
02/23/2022

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 15654336
    Entesarian et al. (2005) report 16 individuals from two extended families of Swedish origin with full penetrant aplasia of lacrimal and salivary glands (ALSG). The 12 affected members of family 1 (4 generations) had a 53 kb deletion including exons 2 and 3, without the involvement of any flanking genes. In family 2 (3 generations) , a nonsense variant in exon 3 (R193X; c.577C>T) was identified in the four affected members.
  • PUBMED: 16630169
    Milunsky et al. (2006) identified a nonsense mutation (K137X) in exon 2 of FGF10 (Family 2) in a 19-year-old mother with ALSG and her 2-year-old daughter with Lacrimoauriculodentodigital (LADD) syndrome. This variant was not found in 200 controls. The author concluded that ALSG and LADD syndrome may represent variable presentations of the same clinical spectrum caused by FGF10 mutations.
  • PUBMED: 19102732
    Scheckenbach et al. (2008) identified the 1st splicing variant (c.430-1 G>A) in FGF10 gene, which led to an alternative acceptor site for exon 3 and premature stop codon, in 2 affected brothers with ALSG, but not in 193 controls. Patients’ father, grandma and grandaunt were all affected, but not available for testing. Deceased relatives showed no additional features of LADD.
HI Evidence Comments:
The disease term associated with this haploinsufficiency score is LADD (lacrimalauriculodentaldigital) syndrome, though loss of function variants in this gene have been reported in individuals with both this diagnosis and the diagnosis of ALSG (aplasia of lacrimal and salivary glands); features of these conditions overlap, and individuals within the same family have been reported with both presentations. Studies in mice model demonstrate that two copies of FGF10 are required for the normal development of lacrimal and salivary glands (PMID: 17213838). Different FGF10 LoF variants were described in families with ALSG and LADD syndrome (for example, K137X - rs104893887) and may represent the variable expression of the same disease possibly through the actions of modifier genes (PMID: 26955834). 4. Seymen et al. (2017) (PMID: 26955834) identified a nonsense variant (c.237G>A) in exon 2 in a 4 yro boy, his 8 yro sister and the mother (Turkish family), all affected with ALSG. Mikolajczak et al 2016 (PMID: 27742760) described different FGF10 LoF variants and also a Gly145 amino acid residue the key residue associated with nuclear translocation and related mutations cause reduced secretion, citoplasmatic accumulation and reduced nuclear translocation. Variants at FGF10 nuclear localization signal compromise its nuclear function and are associated with ALSD. Additional evidence suggests that heterozygosity for LOF variants in FGF10 may result in pulmonary phenotypes (an extension of the ALSG/LADD phenotypic spectrum), while compound heterozygous variants may result in a more severe lung phenotype: Klar et al. (2011) (PMID: 21742743) studied the extended familes with ALSG from Etesarian et al. (2005), looking for the role of FGF10 in the development and function of the lungs and a predisposition to chronic obstructive pulmonary disease (COPD). In fact, FGF10 insufficient patients showed non-reversible airway obstruction when compared with both predicted reference values and siblings with normal FGF10 alleles, supporting that FGF10 haploinsufficiency is associated with reduced pulmonary function consistent with COPD. Korolak et al. (2019) (PMID: 30639323): To elucidate the genetic cause of human lung development, a total of 26 deceased patients from 23 families with lethal developmental lung disease were tested by microarray, WGS and WES. 5 affected individuals from 4 families were found to be comp heterozygous for coding variants ( including 2 large overlapping deletions, a ns c. 577C>T and a fs c.526delA) and a SNV in the noncoding region of FGF10. All heterozygous carriers of the coding variants including carrier parents have LADD, however without lung phenotype, while heterozygous carriers of the noncoding variants were healthy. Since FGF10 haploinsufficiency can not explain the lung phenotype, the data supported the pathogenicity of FGF10 compound heterozygosity. There have also been reported heterozygous LOF variants in cohorts analyzed for other phenotypes: Silversides et al. (2012) (PMID: 22912587) did microarray analysis on a cohort study of 433 patients with Tetralogy of Fallot and/or pulmonary atresia and identified a patient with a small deletion (135kb) involving the entire FGF10 gene. The patient did not meet criteria for LADD syndrome or ALSG. Lee et al. (2017) (PMID: 29215649) performed a 20-gene massive parallel sequencing panel (including FGF10 gene) on 309 Australian and New Zealand patients with craniosynostosis and identified a nonsense variant and a frameshift variants in 2 patients.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000005.9) (NC_000005.10)