• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
FH (HGNC:3700) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
fumarate hydratase
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
15.21(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.09(Read more about gnomAD pLI score)
LOEUF
0.54(Read more about gnomAD LOEUF score)
Cytoband
1q43
Genomic Coordinates
GRCh37/hg19: chr1:241660903-241683055 NCBI Ensembl UCSC
GRCh38/hg38: chr1:241497603-241519755 NCBI Ensembl UCSC
MANE Select Transcript
NM_000143.4 ENST00000366560.4 (Read more about MANE Select)
Function
Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:30761759). Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable). {ECO:0000269|PubMed:30761759, ECO:0000305}. [Isoform Mitochondrial]: Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH. {ECO... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-32383
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/06/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • hereditary leiomyomatosis and renal cell cancer Monarch
HI Evidence:
  • PUBMED: 21398687
    Gardie et al. (2011) identified 32 different heterozygous germline mutations (15 missense, 6 frameshifts, 4 nonsense, 1 deletion/insertion, 5 splicing site and 1 complete deletion). 40 of the 56 families with proven Hereditary Leiomyomatosis and Renal Cell Cancer. Lymphoblstoid cell lines were generated by Epstein-Barr virus transformation of leucocytes. FH enzyme activity was measured spectrophotometrically. A reduction of at least 50% of the enzymatic activity was observed for all mutations tested. A difference of enzyme activities between missense mutations and loss of function mutations (deletions, nonsense mutations, splice site mutations) was NOT observed.
HI Evidence Comments:
Heterozygous loss of function variants result in autosomal dominant Leiomyomatosis and renal cell cancer. Biallelic variants result in autosomal recessive fumarase deficiency

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
no evidence for triplosensitivity

Genomic View

Select assembly: (NC_000001.10) (NC_000001.11)