• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
FGFR1 (HGNC:3688) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
fibroblast growth factor receptor 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
FLT2, KAL2
Alias symbols
H2, H3, H4, H5, CEK, FLG, BFGFR, N-SAM, CD331
%HI
0.42(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.22(Read more about gnomAD LOEUF score)
Cytoband
8p11.23
Genomic Coordinates
GRCh37/hg19: chr8:38268661-38326153 NCBI Ensembl UCSC
GRCh38/hg38: chr8:38411143-38468635 NCBI Ensembl UCSC
MANE Select Transcript
NM_023110.3 ENST00000447712.7 (Read more about MANE Select)
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activati... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-32176
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
04/05/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • hypogonadotropic hypogonadism 2 with or without anosmia Monarch
HI Evidence:
  • PUBMED: 12627230
    Dode et al (2003) used two unrelated individuals with >10Mb deletions overlapping by 540 kb to map the KAL2 (FGFR1) gene and then tested the gene for mutations in other patients. Five loss of function mutations identified in unrelated families. FGFR1 variants found to segregate 10 times with phenotype through several generations across 4 families, although some incomplete penetrance was noted (e.g. a child with hypogonadism + anosmia and a parent with anosmia only).
  • PUBMED: 15605412
    Albuisson et al (2005) describe 7 novel cases and 5 from previous studies (Hardelin et al, Oliveira et al & Soderlund et al) with LoF variants; mostly nonsense. Two of these were sporadic and the rest were familial. There were additionally, two whole gene deletion cases but the extent of the deletions were unknown as the method used was Southern.
  • PUBMED: 19489874
    Barbosa Trarbach et al (2010) describe a whole gene deletion of FGFR1 found by MLPA in a female patient with sporadic normosmic hypogonadotropic hypogonadism and mild dysmorphism. The extent of the deletion is unknown as the method used was MLPA. The study notes that FGFR1 gene deletions do not account for a significant number of sporadic or inherited cases of hypogonadotropic hypogonadism.
HI Evidence Comments:
Loss of function variants in FGFR1 are a well-established cause of hypogonadotropic hypogonadism 2 with or without anosmia or Kallmann syndrome 2 (OMIM 147950) although deletions are rare (PMID: 19489874). Incomplete penetrance is observed. Other phenotypic features include clefting, tooth ageneis and some skeletal anomalies such as syndactyly.

Triplosensitivity (TS) Score Details

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

Genomic View

Select assembly: (NC_000008.10) (NC_000008.11)