ClinGen Dosage Sensitivity Curation Page
FH
- Curation Status: Complete
- id: ISCA-32383
- Date last evaluated: 2020-07-06
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about FH at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/2271
- OMIM: https://omim.org/entry/606812
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK1116/?term=FH%5Bgenesymbol%5D
- ClinGen Haploinsufficiency Score: 3
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 0.149
Select assembly:
(NC_000001.10)
(NC_000001.11)
- Haploinsufficiency score: 3
- Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
- Haploinsufficiency Phenotype: HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CANCER; HLRCC , FUMARASE DEFICIENCY; FMRD
| PubMed ID | Description |
|---|---|
| 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. |
Haploinsufficiency phenotype comments:
Heterozygous loss of function variants result in autosomal dominant Leiomyomatosis and renal cell cancer. Biallelic variants result in autosomal recessive fumarase deficiency
- Triplosensitivity score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
| PubMed ID | Description |
|---|---|
| N/A | |
Triplosensitivity phenotype comment:
no evidence for triplosensitivity