Gene: FH

Alternate names for this Gene: FMRD|HLRCC|HsFH|LRCC|MCL|MCUL1

Gene Summary: The protein encoded by this gene is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy.

Gene is located in Chromosome: 1

Location in Chromosome : 1q43

Description of this Gene: fumarate hydratase

Type of Gene: protein-coding

rs1031919395 in FH gene and Fumarase deficiency PMID 21929734 2011 Fumarase: a paradigm of dual targeting and dual localized functions.

PMID 27037871 2016 Human Fumarate Hydratase Is Dual Localized by an Alternative Transcription Initiation Mechanism.

PMID 21398687 2011 Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma.

PMID 11865300 2002 Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

PMID 25913776 2016 Isolated cutaneous leiomyosarcoma revealing a novel germline mutation of the fumarate hydratase gene.

PMID 28300276 2017 Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers.

PMID 9635293 1998 Molecular analysis and prenatal diagnosis of human fumarase deficiency.

PMID 25923021 2015 Fumarate Hydratase Mutation in a Young Woman With Uterine Leiomyomas and a Family History of Renal Cell Cancer.

PMID 20549362 2010 Fumaric aciduria: an overview and the first Brazilian case report.

PMID 15937070 2006 Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.

PMID 16288654 2005 The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency.

PMID 21404119 2011 Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics.

PMID 25477250 2015 Hereditary leiomyomatosis associated with renal cell carcinoma.

PMID 18313410 2008 Differential metabolic consequences of fumarate hydratase and respiratory chain defects.

PMID 22127509 2012 Familial renal cancer as an indicator of hereditary leiomyomatosis and renal cell cancer syndrome.

PMID 20618355 2011 Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis.

PMID 17960613 2008 "A cancer-predisposing ""hot spot"" mutation of the fumarase gene creates a dominant negative protein."

PMID 21445611 2011 Structural basis of fumarate hydratase deficiency.

PMID 12772087 2003 Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America.

PMID 21520333 2011 LOVD v.2.0: the next generation in gene variant databases.

PMID 16597677 2006 Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.

PMID 24441663 2014 Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry.

PMID 12761039 2003 Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

PMID 16575891 2006 Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1.

PMID 22069215 2012 Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency.

PMID 22595425 2012 Mild fumarase deficiency and a trial of low protein diet.

PMID 28747166 2017 Cascade Fumarate Hydratase mutation screening allows early detection of kidney tumour: a case report.

PMID 15221078 2004 A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency.

PMID 16876016 2006 Fumarate hydratase deficiency in monozygotic twins.

PMID 10896297 2000 Abnormalities in succinylpurines in fumarase deficiency: possible role in pathogenesis of CNS impairment.

PMID 17182618 2007 Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF.

PMID 16151915 2005 Fumarase deficiency presenting with periventricular cysts.

PMID 15987702 2005 Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations.

PMID 23612258 2013 Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene.

PMID 9300800 1997 Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human.

PMID 24182348 2013 Fumarase deficiency in dichorionic diamniotic twins.

PMID 16510303 2006 Molecular and biochemical investigations in fumarase deficiency.

PMID 30050099 2019 Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma.

PMID 26457356 2015 Morphology and Immunohistochemistry for 2SC and FH Aid in Detection of Fumarate Hydratase Gene Aberrations in Uterine Leiomyomas From Young Patients.

PMID 17392716 2007 Hereditary leiomyomatosis and renal cell cancer: an unusual and aggressive form of hereditary renal carcinoma.

PMID 25004247 2014 Germline FH mutations presenting with pheochromocytoma.

PMID 14632190 2003 Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata.

PMID 15761418 2005 Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata.

PMID 2314594 1990 Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes.

PMID 26574848 2016 Fumarate Hydratase-deficient Uterine Leiomyomas Occur in Both the Syndromic and Sporadic Settings.

PMID 16206287 2006 Modeling tumor predisposing FH mutations in yeast: effects on fumarase activity, growth phenotype and gene expression profile.

PMID 19470762 2009 Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species.

PMID 25750977 2015 An unusual case of sporadic hereditary leiomyomatosis and renal cell carcinoma syndrome.

PMID 22764886 2013 Fumarate hydratase gene mutation in two young patients with sporadic uterine fibroids.

PMID 22565324 2012 Bilateral ovarian steroid cell tumours and massive macronodular adrenocortical disease in a patient with hereditary leiomyomatosis and renal cell cancer syndrome.

PMID 22243733 2012 JAAD Grand Rounds quiz. A 46-year-old man with agminated papules on the buttock. Reed syndrome.

PMID 25292446 2014 Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.

PMID 16237213 2005 Missense mutations in fumarate hydratase in multiple cutaneous and uterine leiomyomatosis and renal cell cancer.

PMID 19967458 2010 Hereditary leiomyomatosis and renal cell carcinoma: very early diagnosis of renal cancer in a paediatric patient.

rs121913119 in FH gene and Hereditary Leiomyomatosis and Renal Cell Cancer PMID 26237645 2015 Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation.

PMID 11865300 2002 Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

PMID 8200987 1994 Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.

PMID 25394175 2015 A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

PMID 24319509 2013 Canadian guideline on genetic screening for hereditary renal cell cancers.

rs1060499635 in FH gene and Neoplastic Syndromes, Hereditary PMID 22982371 2013 Adrenal nodular hyperplasia in hereditary leiomyomatosis and renal cell cancer.

PMID 24419633 2014 Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of recombinant human fumarase.

PMID 20618355 2011 Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis.

PMID 22561013 2012 Conformational changes upon ligand binding in the essential class II fumarase Rv1098c from Mycobacterium tuberculosis.

PMID 21398687 2011 Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma.

PMID 15937070 2006 Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.

PMID 21445611 2011 Structural basis of fumarate hydratase deficiency.

PMID 9665847 1998 Crystal structures of native and recombinant yeast fumarase.

PMID 21904061 2011 Structure of fumarate hydratase from Rickettsia prowazekii, the agent of typhus and suspected relative of the mitochondria.

PMID 25923021 2015 Fumarate Hydratase Mutation in a Young Woman With Uterine Leiomyomas and a Family History of Renal Cell Cancer.

PMID 16597677 2006 Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.

PMID 11865300 2002 Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

PMID 16029320 2005 Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer.

PMID 23211287 2013 Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome.

PMID 24625422 2014 Hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a rapid autopsy report of metastatic renal cell carcinoma.

PMID 21630274 2011 Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status.

PMID 12761039 2003 Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

PMID 26900816 2016 Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.

PMID 16757530 2006 Adult leydig cell tumors of the testis caused by germline fumarate hydratase mutations.

PMID 19939761 2010 Clinical and molecular genetic aspects of hereditary multiple cutaneous leiomyomatosis.

PMID 12183404 2002 Few FH mutations in sporadic counterparts of tumor types observed in hereditary leiomyomatosis and renal cell cancer families.

PMID 25477250 2015 Hereditary leiomyomatosis associated with renal cell carcinoma.

PMID 16155190 2006 Increased risk of cancer in patients with fumarate hydratase germline mutation.

PMID 12772087 2003 Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America.

PMID 27051714 2015 Reed syndrome presenting with leiomyosarcoma.

PMID 21733559 2011 Renal medullary carcinomas: histopathologic phenotype associated with diverse genotypes.

PMID 18176756 2008 Single base mutation in the fumarate hydratase gene leading to segmental cutaneous leiomyomatosis.

PMID 21404119 2011 Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics.

PMID 25012257 2014 Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment.

PMID 22595425 2012 Mild fumarase deficiency and a trial of low protein diet.

PMID 15987702 2005 Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations.

PMID 22069215 2012 Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency.

PMID 16237213 2005 Missense mutations in fumarate hydratase in multiple cutaneous and uterine leiomyomatosis and renal cell cancer.

PMID 16575891 2006 Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1.

PMID 25637381 2015 Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

PMID 21560188 2011 Clinical and biochemical heterogeneity associated with fumarase deficiency.

PMID 21340633 2011 High-throughput structural biology of metabolic enzymes and its impact on human diseases.

PMID 19151755 2009 Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas.

PMID 28747166 2017 Cascade Fumarate Hydratase mutation screening allows early detection of kidney tumour: a case report.

PMID 16876016 2006 Fumarate hydratase deficiency in monozygotic twins.

PMID 18313410 2008 Differential metabolic consequences of fumarate hydratase and respiratory chain defects.

PMID 15221078 2004 A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency.

PMID 10896297 2000 Abnormalities in succinylpurines in fumarase deficiency: possible role in pathogenesis of CNS impairment.

PMID 22764886 2013 Fumarate hydratase gene mutation in two young patients with sporadic uterine fibroids.

PMID 16151915 2005 Fumarase deficiency presenting with periventricular cysts.

PMID 24441663 2014 Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry.

PMID 16510303 2006 Molecular and biochemical investigations in fumarase deficiency.

PMID 25985877 2015 Genetic testing of leiomyoma tissue in women younger than 30 years old might provide an effective screening approach for the hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC).

PMID 9300800 1997 Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human.

PMID 23612258 2013 Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene.

PMID 9635293 1998 Molecular analysis and prenatal diagnosis of human fumarase deficiency.

PMID 24182348 2013 Fumarase deficiency in dichorionic diamniotic twins.

PMID 18366737 2008 The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency.

PMID 16639410 2006 Germline fumarate hydratase mutations in patients with ovarian mucinous cystadenoma.

PMID 22703879 2012 Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

PMID 17392716 2007 Hereditary leiomyomatosis and renal cell cancer: an unusual and aggressive form of hereditary renal carcinoma.

PMID 25004247 2014 Germline FH mutations presenting with pheochromocytoma.

PMID 20549362 2010 Fumaric aciduria: an overview and the first Brazilian case report.

PMID 15761418 2005 Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata.

PMID 18514489 2008 Hereditary multiple cutaneous leiomyoma resulting from novel mutations in the fumarate hydratase gene.

PMID 22086304 2012 Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance.

PMID 15663510 2005 Familial multiple cutaneous and uterine leiomyomas associated with papillary renal cell cancer.

PMID 25750977 2015 An unusual case of sporadic hereditary leiomyomatosis and renal cell carcinoma syndrome.

PMID 14632190 2003 Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata.

PMID 26023681 2015 Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.

PMID 22565324 2012 Bilateral ovarian steroid cell tumours and massive macronodular adrenocortical disease in a patient with hereditary leiomyomatosis and renal cell cancer syndrome.

PMID 24684806 2014 Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas.

PMID 21051878 2010 A novel missense mutation in fumarate hydratase in an Italian patient with a diffuse variant of cutaneous leiomyomatosis (Reed's syndrome).

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 23320739 2013 Hereditary papillary renal cell carcinoma primarily diagnosed in a cervical lymph node: a case report of a 30-year-old woman with multiple metastases.