MCID: FMR011
MIFTS: 58

Fumarate Hydratase Deficiency malady

Genetic diseases, Rare diseases, Neuronal diseases categories

Summaries for Fumarate Hydratase Deficiency

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44NIH Rare Diseases, 22Genetics Home Reference, 66Wikipedia, 48OMIM, 20GeneReviews, 34MalaCards
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Genetics Home Reference:22 Fumarase deficiency is a condition that primarily affects the nervous system, especially the brain. Affected infants may have an abnormally small head size (microcephaly), abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may also experience seizures. Some people with this disorder have unusual facial features, including a prominent forehead (frontal bossing), low-set ears, a small jaw (micrognathia), widely spaced eyes (ocular hypertelorism), and a depressed nasal bridge. An enlarged liver and spleen (hepatosplenomegaly) may also be associated with this disorder, as well as an excess of red blood cells (polycythemia) or deficiency of white blood cells (leukopenia) in infancy. Affected individuals usually survive only a few months, but a few have lived into early adulthood.

MalaCards: Fumarate Hydratase Deficiency, also known as fumarase deficiency, is related to kidney cancer and leiomyomatosis. An important gene associated with Fumarate Hydratase Deficiency is FH (fumarate hydratase), and among its related pathways are Trk receptor signaling mediated by the MAPK pathway and PDGFR-alpha signaling pathway. The compounds pilocarpine and cocl2 have been mentioned in the context of this disorder. Affiliated tissues include brain and kidney, and related mouse phenotypes are renal/urinary system and limbs/digits/tail.

NIH Rare Diseases:44 Fumarase deficiency is an inherited condition that primarily affects the nervous system, especially the brain. affected infants may have microcephaly, abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), failure to thrive, seizures, and/or distinctive facial features. other signs and symptoms may include hepatosplenomegaly, an excess of red blood cells (polycythemia), and/or or deficiency of white blood cells (leukopenia). affected individuals usually survive only a few months, but a few have lived into early adulthood. this condition is caused by mutations in the fh gene and is inherited in an autosomal recessive manner. no effective treatment is currently available. last updated: 11/6/2012

Wikipedia:66 Fumarase deficiency (or fumaric aciduria), also known as \"Polygamist Down\'s\", is an autosomal... more...

Description from OMIM:48 606812

GeneReviews summary for fum

Aliases & Classifications for Fumarate Hydratase Deficiency

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20GeneReviews, 44NIH Rare Diseases, 21GeneTests, 23GTR, 22Genetics Home Reference, 48OMIM, 46Novoseek, 50Orphanet, 63UMLS, 37MESH via Orphanet, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

50
fumarase deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy; Age of death: Before age 5


Aliases & Descriptions:

fumarate hydratase deficiency 20 44 21 22
fumarase deficiency 20 44 23 22 48 46 50 63
fumaric aciduria 20 44 22 50 63


External Ids:

OMIM48 606812
MESH via Orphanet37 C538191
ICD10 via Orphanet27 E88.8
SNOMED-CT via Orphanet60 124616002, 237983002
UMLS via Orphanet64 C0342770, C2936826

Related Diseases for Fumarate Hydratase Deficiency

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18GeneCards, 19GeneDecks
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Diseases related to Fumarate Hydratase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 43)
idRelated DiseaseScoreTop Affiliating Genes
1kidney cancer30.8VHL, FH
2leiomyomatosis30.7VHL, FH
3hypoxia10.5
4leiomyoma10.3
5renal cell carcinoma10.3
6uterine fibroid10.3
7polyhydramnios10.1
8biliary atresia10.1
9cerebritis10.1
10mitochondrial encephalomyopathy10.1
11encephalomyopathy10.1
12hypotonia10.1
13cystadenoma10.1VHL
14hereditary leiomyomatosis and renal cell cancer10.1FH, HIF1A
15familial colorectal cancer10.0VHL, FH
16cystic kidney10.0VHL, FH
17oxyphilic adenoma10.0VHL, FH
18hemangioblastoma10.0HIF1A, VHL
19erythrocytosis10.0HIF1A, VHL
20von hippel-lindau disease10.0HIF1A, VHL
21polycythemia10.0HIF1A, VHL
22diabetic retinopathy10.0HIF1A, SRF
23paraganglioma10.0VHL, FH, HIF1A
24glioblastoma multiforme10.0VHL, HIF1A
25renal clear cell carcinoma10.0HIF1A, FH, VHL
26kidney rhabdoid cancer10.0VHL, FH, HIF1A
27t-cell leukemia10.0FOS, SRF, JUNB
28stomach cancer10.0VHL, JUNB, HIF1A
29hypertrophy of breast10.0FOS, SRF, JUNB
30retinoblastoma9.9JUNB, FOS, VHL
31astrocytoma9.9HIF1A, FOS, VHL
32adenocarcinoma9.9HIF1A, JUNB, SRF, VHL
33rheumatoid arthritis9.9FOS, SRF, JUNB
34ovarian cancer9.9FOS, SRF, HIF1A
35osteosarcoma9.9HIF1A, JUNB, SRF, FOS
36hepatocellular carcinoma9.9HIF1A, JUNB, SRF, FOS
37colon cancer9.9HIF1A, SRF, FOS
38lung cancer9.9VHL, SRF, HIF1A
39malignant glioma9.9VHL, FOS, JUNB, HIF1A
40burkitt's lymphoma9.9JUNB, SRF, FOS, VHL
41tongue squamous cell carcinoma9.9HIF1A, SRF, FOS, VHL
42pheochromocytoma9.9HIF1A, JUNB, FOS, FH, VHL
43breast cancer9.8VHL, FOS, SRF, JUNB, HIF1A

Graphical network of the top 20 diseases related to Fumarate Hydratase Deficiency:



Diseases related to fumarate hydratase deficiency

Symptoms for Fumarate Hydratase Deficiency

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48OMIM
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Symptoms by clinical synopsis from OMIM:

606812

Clinical features from OMIM:

606812

Drugs & Therapeutics for Fumarate Hydratase Deficiency

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-RT
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Approved drugs:

Search CenterWatch for Fumarate Hydratase Deficiency

Drug clinical trials:

Search ClinicalTrials for Fumarate Hydratase Deficiency

Search NIH Clinical Center for Fumarate Hydratase Deficiency

Search CenterWatch for Fumarate Hydratase Deficiency

Genetic Tests for Fumarate Hydratase Deficiency

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21GeneTests, 23GTR
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Genetic tests related to Fumarate Hydratase Deficiency:

id Genetic test Affiliating Genes
1 Fumarate Hydratase Deficiency21 FH
2 Fumarase Deficiency23

Anatomical Context for Fumarate Hydratase Deficiency

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34MalaCards
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MalaCards organs/tissues related to Fumarate Hydratase Deficiency:

34
Brain, Kidney

Animal Models for Fumarate Hydratase Deficiency or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Fumarate Hydratase Deficiency:

38 (show all 13)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053678.3HIF1A, JUNB, FH, VHL
2MP:00053718.3VHL, FOS, JUNB, HIF1A
3MP:00053808.3VHL, FOS, SRF, HIF1A
4MP:00020068.2HIF1A, JUNB, FOS, VHL
5MP:00107718.1HIF1A, JUNB, FOS, VHL
6MP:00028738.1HIF1A, SRF, FOS, VHL
7MP:00053858.1VHL, SRF, JUNB, HIF1A
8MP:00053907.8HIF1A, JUNB, SRF, FOS, VHL
9MP:00053977.7VHL, FOS, SRF, JUNB, HIF1A
10MP:00053877.6VHL, FOS, SRF, JUNB, HIF1A
11MP:00053847.4VHL, FH, FOS, SRF, JUNB, HIF1A
12MP:00053767.4HIF1A, JUNB, SRF, FOS, FH, VHL
13MP:00107687.3HIF1A, JUNB, SRF, FOS, FH, VHL

Publications for Fumarate Hydratase Deficiency

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53PubMed
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Articles related to Fumarate Hydratase Deficiency:

(show all 18)
idTitleAuthorsYear
1
Molecular pathways: Fumarate hydratase-deficient kidney cancer--targeting the Warburg effect in cancer. (23633457)
2013
2
Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency. (23499446)
2013
3
A novel fumarate hydratase-deficient HLRCC kidney cancer cell line, UOK268: a model of the Warburg effect in cancer. (22867999)
2012
4
The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels. (21907923)
2011
5
Structural basis of fumarate hydratase deficiency. (21445611)
2011
6
Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism. (20660115)
2010
7
Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis. (20978192)
2010
8
UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer. (19963135)
2010
9
Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas. (19151755)
2009
10
Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species. (19470762)
2009
11
Fumarate hydratase deficiency and cancer: activation of hypoxia signaling? (17418405)
2007
12
Distinct expression profile in fumarate-hydratase-deficient uterine fibroids. (16319128)
2006
13
Fumarate hydratase deficiency in monozygotic twins. (16876016)
2006
14
Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. (12761039)
2003
15
Fumarate hydratase deficiency: increased fumaric acid in amniotic fluid of two affected pregnancies. (11117439)
2000
16
Fumarate hydratase deficiency. (9700607)
1998
17
Fumarate Hydratase Deficiency (20301679)
1993
18
Variability of clinical presentation in fumarate hydratase deficiency. (1432428)
1992

Variations for Fumarate Hydratase Deficiency

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Fumarate Hydratase Deficiency:

65
id Symbol AA change Variation ID SNP ID
1FHp.Lys230ArgVAR_002445
2FHp.Ala308ThrVAR_002446
3FHp.Phe312CysVAR_002447
4FHp.Asp425ValVAR_002448

Clinvar genetic disease variations for Fumarate Hydratase Deficiency:

1
id Gene Name Type Significance SNP ID Assembly Location
1FHNM_000143.3(FH): c.793G> A (p.Ala265Thr)single nucleotide variantPathogenicrs387906545GRCh37Chr 1, 241669414: 241669414
2FHNM_000143.3(FH): c.1084G> C (p.Glu362Gln)single nucleotide variantPathogenicrs121913119GRCh37Chr 1, 241667366: 241667366
3FHNM_000143.3(FH): c.521C> G (p.Pro174Arg)single nucleotide variantPathogenicrs199822819GRCh37Chr 1, 241675301: 241675301
4FHFH, DELdeletionPathogenic
5FHNM_000143.3(FH): c.1127A> C (p.Gln376Pro)single nucleotide variantPathogenicrs200796606GRCh37Chr 1, 241665852: 241665852
6FHNM_000143.3(FH): c.1431_1433dupAAA (p.Lys477_Asn478insLys)duplicationPathogenicrs367543046GRCh37Chr 1, 241661228: 241661230

Expression for genes affiliated with Fumarate Hydratase Deficiency

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Fumarate Hydratase Deficiency

Search GEO for disease gene expression data for Fumarate Hydratase Deficiency.

Pathways for genes affiliated with Fumarate Hydratase Deficiency

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Sources:
51PathCards, 39NCBI BioSystems Database, 56Reactome, 61Thomson Reuters, 54QIAGEN, 62Tocris Bioscience, 5Cell Signaling Technology, 31KEGG, 58SinoBiological, 55R&D Systems, 52PharmGKB
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Pathways related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show all 40)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.4SRF, FOS
29.4FOS, SRF
39.4SRF, FOS
49.4FOS, SRF
59.4FOS, SRF
6
Show member pathways
9.4SRF, FOS
7
Show member pathways
9.4FOS, SRF
89.4HIF1A, VHL
9
Show member pathways
VEGFR1 specific signals39
9.4VHL, HIF1A
109.4VHL, HIF1A
119.4HIF1A, VHL
129.4HIF1A, VHL
13
Show member pathways
9.4VHL, HIF1A
14
Show member pathways
Development Ligand dependent activation of the ESR1 AP 1 pathway61
9.3FOS, HIF1A
15
Show member pathways
9.3FOS, HIF1A
169.3HIF1A, FOS
17
Show member pathways
9.3FOS, HIF1A
18
Show member pathways
Immune response IL 3 activation and signaling pathway61
9.1FOS, JUNB
19
Show member pathways
9.1FOS, JUNB
20
Show member pathways
Immune response MIF in innate immunity response61
9.1FOS, JUNB
219.1FOS, JUNB
229.1JUNB, FOS
23
Show member pathways
MAPK Cascade39
Immune response Oncostatin M signaling via MAPK in human cells61
Oncostatin M Signaling Pathway39
9.1FOS, JUNB
249.1JUNB, FOS
259.1FOS, JUNB
26
Show member pathways
Ras signaling in the CD4+ TCR pathway39
9.1FOS, JUNB
27
Show member pathways
9.1FOS, JUNB
289.1FOS, JUNB
299.1JUNB, FOS
309.1FOS, JUNB
31
Show member pathways
Calcium signaling in the CD4+ TCR pathway39
9.1JUNB, FOS
32
Show member pathways
IL27-mediated signaling events39
9.1JUNB, FOS
339.1JUNB, FOS
349.0HIF1A, FH, VHL
35
Show member pathways
8.9HIF1A, FOS, VHL
36
Show member pathways
8.6FOS, SRF, JUNB
37
Show member pathways
8.6FOS, SRF, JUNB
38
Show member pathways
Transcription Receptor mediated HIF regulation61
Development CNTF receptor signaling61
Class IB PI3K non-lipid kinase events39
ErbB2/ErbB3 signaling events39
Development Growth hormone signaling via PI3K AKT and MAPK cascades61
Translation Regulation activity of EIF261
Regulation of lipid metabolism Insulin signaling generic cascades61
Transcription PPAR Pathway61
Cell adhesion PLAU signaling61
Translation Regulation activity of EIF4F61
8.5HIF1A, JUNB, FOS
398.5VHL, FH, FOS, HIF1A
40
Show member pathways
7.5HIF1A, JUNB, SRF, FOS, VHL

Compounds for genes affiliated with Fumarate Hydratase Deficiency

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46Novoseek, 30IUPHAR, 12DrugBank, 52PharmGKB, 25HMDB, 62Tocris Bioscience, 3BitterDB
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Compounds related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show top 50)    (show all 65)
idCompoundScoreTop Affiliating Genes
1pilocarpine46 30 1211.8FOS, SRF
2cocl2469.8VHL, HIF1A
3cobalt chloride469.8HIF1A, VHL
4sunitinib46 52 1211.7VHL, HIF1A
5deferoxamine46 1210.7HIF1A, VHL
6cobalt46 2510.6VHL, HIF1A
7bapta469.6FOS, HIF1A
8sch 39166469.6FOS, JUNB
9sch 23390469.5FOS, JUNB
10dizocilpine469.5FOS, JUNB
11fumarate46 1210.4VHL, FH, HIF1A
12alpha-ketoglutarate469.4HIF1A, FH, VHL
13succinate469.4VHL, FH, HIF1A
14naloxone46 30 52 1212.3FOS, JUNB
15agar469.2FOS, SRF, HIF1A
16ly294002469.2HIF1A, FOS, VHL
17amphetamine46 52 1211.1JUNB, FOS
18lactate469.1HIF1A, SRF, FH
19iron46 2510.1VHL, SRF, HIF1A
20superoxide46 2510.0HIF1A, SRF, FH
21capsaicin46 3010.0FOS, HIF1A
22ionomycin469.0FOS, SRF, JUNB
2312-o-tetradecanoylphorbol 13-acetate469.0FOS, SRF, JUNB
24nmda46 309.9JUNB, SRF, FOS
25forskolin46 52 1210.9JUNB, SRF, FOS
26proline468.9HIF1A, SRF, FH, VHL
27arachidonic acid46 30 25 1211.9FOS, SRF, JUNB
28thymidine46 259.9FOS, SRF, HIF1A
29sb 20358046 629.9FOS, JUNB, HIF1A
30tamoxifen46 52 30 1211.8HIF1A, JUNB, FOS
31oxygen46 259.8HIF1A, SRF, FH, VHL
32pd 98,059468.8FOS, JUNB, HIF1A
33vegf468.7HIF1A, SRF, FOS, VHL
34cyclosporin a46 30 6210.7HIF1A, JUNB, SRF
35cyclic amp46 259.6FOS, SRF, JUNB
36leucine468.5FOS, SRF, JUNB
37actinomycin d468.5VHL, FOS, JUNB, HIF1A
38atp46 309.5HIF1A, JUNB, SRF, FH
39genistein46 30 62 3 25 1213.4HIF1A, JUNB, SRF, FOS
40pge2468.4HIF1A, JUNB, SRF, FOS
41cycloheximide468.4HIF1A, JUNB, SRF, FOS
42dexamethasone46 52 30 1211.4HIF1A, JUNB, SRF, FOS
43threonine468.4HIF1A, JUNB, SRF, FOS
44retinoic acid46 259.3FOS, SRF, JUNB, HIF1A
45glucose468.1HIF1A, JUNB, SRF, FH, VHL
46oligonucleotide468.0HIF1A, JUNB, SRF, FOS, VHL
47phosphatidylinositol468.0VHL, FOS, SRF, JUNB, HIF1A
48estrogen468.0HIF1A, JUNB, SRF, FOS, VHL
49serine467.9HIF1A, JUNB, SRF, FOS, VHL
50tyrosine467.6HIF1A, JUNB, SRF, FOS, FH, VHL

GO Terms for genes affiliated with Fumarate Hydratase Deficiency

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17Gene Ontology
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Cellular components related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1nucleoplasmGO:0056548.0VHL, FOS, JUNB, HIF1A
2nucleolusGO:0057307.8HIF1A, JUNB, FOS, VHL
3nucleusGO:0056347.5VHL, FOS, SRF, JUNB, HIF1A

Biological processes related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show all 18)
idNameGO IDScoreTop Affiliating Genes
1regulation of transcription from RNA polymerase II promoter in response to hypoxiaGO:0614189.6HIF1A, VHL
2mRNA transcription from RNA polymerase II promoterGO:0427899.6SRF, HIF1A
3muscle cell cellular homeostasisGO:0467169.6HIF1A, SRF
4response to light stimulusGO:0094169.4JUNB, FOS
5heart loopingGO:0019479.4HIF1A, SRF
6cellular response to hypoxiaGO:0714569.4VHL, HIF1A
7trophectodermal cell differentiationGO:0018299.4JUNB, SRF
8response to corticosteroneGO:0514129.4FOS, JUNB
9cellular response to hormone stimulusGO:0328709.3FOS, JUNB
10response to progesteroneGO:0325709.3FOS, JUNB
11cellular response to calcium ionGO:0712779.3JUNB, FOS
12response to cAMPGO:0515919.2FOS, JUNB
13response to mechanical stimulusGO:0096129.1FOS, JUNB
14response to toxic substanceGO:0096369.1FOS, SRF
15positive regulation of cell differentiationGO:0455979.0VHL, SRF, JUNB
16response to cytokineGO:0340978.9JUNB, SRF, FOS
17positive regulation of transcription, DNA-templatedGO:0458938.8HIF1A, FOS, VHL
18positive regulation of transcription from RNA polymerase II promoterGO:0459448.3FOS, SRF, JUNB, HIF1A

Molecular functions related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1RNA polymerase II transcription factor binding transcription factor activityGO:0010769.4SRF, HIF1A
2RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcriptionGO:0010779.2SRF, HIF1A
3double-stranded DNA bindingGO:0036909.1FOS, JUNB
4RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:0037059.0SRF, HIF1A
5transcription factor bindingGO:0081348.5VHL, FOS, SRF, HIF1A
6sequence-specific DNA binding transcription factor activityGO:0037008.0HIF1A, JUNB, SRF, FOS

Products for genes affiliated with Fumarate Hydratase Deficiency

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  • Antibodies
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Sources for Fumarate Hydratase Deficiency

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet