FH |
- 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)