MCID: FMR011
MIFTS: 62

Fumarate Hydratase Deficiency malady

Neuronal diseases, Metabolic diseases categories

Summaries for Fumarate Hydratase Deficiency

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21Genetics Home Reference, 42NIH Rare Diseases, 63Wikipedia, 46OMIM, 19GeneReviews, 32MalaCards
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Genetics Home Reference:21 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 Cellular response to hypoxia and PDGFR-alpha signaling pathway. The compounds egcg and pge2 have been mentioned in the context of this disorder. Affiliated tissues include brain, liver and eye, and related mouse phenotypes are limbs/digits/tail and embryogenesis.

NIH Rare Diseases:42 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:63 Fumarase deficiency (or fumaric aciduria), also known as \"Polygamist Down\'s\", is an autosomal... more...

Description from OMIM:46 606812

GeneReviews summary for fum

Aliases & Classifications for Fumarate Hydratase Deficiency

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19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 48Orphanet, 60UMLS, 22GTR, 46OMIM, 44Novoseek, 35MESH via Orphanet, 26ICD10 via Orphanet, 57SNOMED-CT via Orphanet, 61UMLS via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Metabolic diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

48
fumarase deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy; Age of death: Before age 5


Aliases & Descriptions:

fumarate hydratase deficiency 19 42 20 21
fumarase deficiency 19 42 22 21 46 44 48 60
fumaric aciduria 19 42 21 48 60


External Ids:

OMIM46 606812
MESH via Orphanet35 C538191
ICD10 via Orphanet26 E88.8
SNOMED-CT via Orphanet57 124616002, 237983002
UMLS via Orphanet61 C0342770, C2936826

Related Diseases for Fumarate Hydratase Deficiency

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17GeneCards, 18GeneDecks
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Diseases related to Fumarate Hydratase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 76)
idRelated DiseaseScoreTop Affiliating Genes
1kidney cancer30.7VHL, HIF1A, FOS, FH
2leiomyomatosis30.6VHL, FH
3leiomyoma30.4FH
4hereditary leiomyomatosis and renal cell cancer30.4FH
5hereditary renal cell carcinoma10.3
6renal cell carcinoma10.3
7uterine fibroid10.3
8biliary atresia10.1
9cerebritis10.1
10polyhydramnios10.1
11mitochondrial encephalomyopathy10.1
12cystadenoma10.0VHL
13peutz-jeghers syndrome10.0VHL
14hemangioma10.0VHL
15primary hyperoxaluria10.0FOS
16neuroblastoma10.0TP53
17multiple myeloma10.0TP53
18colon adenocarcinoma10.0FOS
19thyroid cancer10.0TP53
20esophageal cancer10.0TP53
21sarcoma10.0TP53
22obesity10.0PRKAB1, HIF1A
23osteoarthritis10.0JUNB
24familial colorectal cancer10.0FH, VHL
25hemangioblastoma10.0HIF1A, VHL
26cystic kidney10.0VHL, FH
27von hippel-lindau disease10.0HIF1A, VHL
28hyperglycemia10.0PRKAB1, HIF1A
29gastric ulcer10.0SRF
30insulin resistance10.0FOS, PRKAB1
31psoriasis10.0JUNB
32tuberous sclerosis10.0VHL, PRKAB1
33multiple sclerosis10.0SRF
34fibrosarcoma10.0FOS, HIF1A
35oral cancer10.0TP53, HIF1A
36erythrocytosis10.0HIF1A, VHL
37endometriosis10.0SRF
38fibrous dysplasia10.0FOS
39myeloid leukemia10.0FOS, JUNB
40kidney rhabdoid cancer10.0FH, VHL, HIF1A
41renal clear cell carcinoma10.0HIF1A, FH, VHL
42paraganglioma10.0FH, HIF1A, VHL
43oxyphilic adenoma10.0VHL, FH
44atherosclerosis10.0SRF, PRKAB1
45pancreatic cancer10.0HIF1A, TP53
46bladder carcinoma10.0FH, TP53
47deficiency anemia10.0SRF, HIF1A
48ischemia10.0HIF1A, JUNB, PRKAB1
49asthma10.0FOS, SRF
50vascular disease10.0FOS, TP53, HIF1A

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



Diseases related to fumarate hydratase deficiency

Clinical Features for Fumarate Hydratase Deficiency

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46OMIM
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Clinical features from OMIM:

606812

Clinical synopsis from OMIM:

606812

Drugs & Therapeutics for Fumarate Hydratase Deficiency

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-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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20GeneTests, 22GTR
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Genetic tests related to Fumarate Hydratase Deficiency:

id Genetic test Affiliating Genes
1 Fumarate Hydratase Deficiency20 FH
2 Fumarase Deficiency22

Anatomical Context for Fumarate Hydratase Deficiency

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32MalaCards
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MalaCards organs/tissues related to Fumarate Hydratase Deficiency:

32
Brain, Liver, Eye, Spleen, Kidney

Animal Models for Fumarate Hydratase Deficiency or affiliated genes

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36MGI
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MGI Mouse Phenotypes related to Fumarate Hydratase Deficiency:

36 (show all 16)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:000537110.1JUNB
2MP:00053809.3SRF, VHL
3MP:00053909.3SRF, JUNB
4MP:00020069.2JUNB, VHL, FOS
5MP:00053678.8HIF1A, FH, VHL, JUNB
6MP:00107718.7JUNB, FOS, HIF1A, TP53
7MP:00053708.4VHL, PRKAB1, HIF1A, LDHA, TP53
8MP:00053768.1LDHA, SRF, PRKAB1, FH, JUNB
9MP:00028737.7VHL, FOS, HIF1A, SRF, LDHA, TP53
10MP:00053697.6VHL, PRKAB1, HIF1A, SRF, TP53
11MP:00053857.3JUNB, VHL, HIF1A, SRF, LDHA, TP53
12MP:00053787.1VHL, FOS, PRKAB1, HIF1A, SRF, LDHA
13MP:00053846.9JUNB, VHL, FOS, PRKAB1, HIF1A, SRF
14MP:00053976.7JUNB, VHL, FOS, PRKAB1, HIF1A, SRF
15MP:00053876.7JUNB, VHL, FOS, PRKAB1, HIF1A, SRF
16MP:00107686.4JUNB, VHL, FH, FOS, PRKAB1, HIF1A

Publications for Fumarate Hydratase Deficiency

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50PubMed
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Articles related to Fumarate Hydratase Deficiency:

(show all 20)
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
Cutaneous and uterine leiomyomatosis and ovarian cystadenoma associated with deficiency of fumarate hydratase. (24396716)
2011
6
Structural basis of fumarate hydratase deficiency. (21445611)
2011
7
Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism. (20660115)
2010
8
Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis. (20978192)
2010
9
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
10
Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas. (19151755)
2009
11
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
12
The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. (18366737)
2008
13
Fumarate hydratase deficiency and cancer: activation of hypoxia signaling? (17418405)
2007
14
Distinct expression profile in fumarate-hydratase-deficient uterine fibroids. (16319128)
2006
15
Fumarate hydratase deficiency in monozygotic twins. (16876016)
2006
16
Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. (12761039)
2003
17
Fumarate hydratase deficiency: increased fumaric acid in amniotic fluid of two affected pregnancies. (11117439)
2000
18
Fumarate hydratase deficiency. (9700607)
1998
19
Fumarate Hydratase Deficiency (20301679)
1993
20
Variability of clinical presentation in fumarate hydratase deficiency. (1432428)
1992

Genetic Variations for Fumarate Hydratase Deficiency

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62UniProtKB/Swiss-Prot
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Genetic disease variations for Fumarate Hydratase Deficiency:

62
id Symbol AA change Variation ID SNP ID
1FHp.Lys230ArgVAR_002445
2FHp.Ala308ThrVAR_002446
3FHp.Phe312CysVAR_002447
4FHp.Asp425ValVAR_002448

Expression for genes affiliated with Fumarate Hydratase Deficiency

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1BioGPS, 15Gene 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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53Reactome, 37NCBI BioSystems Database, 12EMD Millipore, 29KEGG, 4Cell Signaling Technology, 51QIAGEN, 52R&D Systems
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Pathways related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show all 25)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Hide members
9.7VHL, HIF1A
29.7SRF
3
Development Leptin signaling via JAK/STAT and MAPK cascades
Hide members
9.5FOS, HIF1A
49.3HIF1A, VHL, LDHA
59.3JUNB, FOS
69.3JUNB, FOS
79.3HIF1A, TP53, VHL
89.3LDHA, FH, PRKAB1
99.2HIF1A, FOS, LDHA
109.1SRF, FOS
11
Immune response IL-6 signaling pathway
Hide members
9.1SRF, FOS
129.1SRF, FOS
138.9HIF1A, TP53, LDHA, VHL
14
Hide members
8.9FOS, TP53, JUNB
15
G-protein signaling Ras family GTPases in kinase cascades (scheme)
Hide members
8.9FOS, JUNB, TP53
16
Hide members
8.8JUNB, FOS, PRKAB1
17
Hide members
8.8TP53, LDHA, PRKAB1, FH
188.7TP53, FOS, SRF
19
Hide members
8.7TP53, SRF, FOS
20
Hide members
8.5FOS, JUNB, SRF
218.5SRF, FOS, JUNB
228.4TP53, VHL, FH, FOS, HIF1A
23
Translation Insulin regulation of translation
Hide members
8.4PRKAB1, FOS, JUNB, HIF1A
24
Hide members
7.6VHL, FH, HIF1A, SRF, TP53, FOS
25
Hide members
6.8HIF1A, JUNB, TP53, SRF, PRKAB1, VHL

Compounds for genes affiliated with Fumarate Hydratase Deficiency

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44Novoseek, 59Tocris Bioscience, 11DrugBank, 24HMDB, 49PharmGKB, 28IUPHAR, 2BitterDB
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Compounds related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show top 50)    (show all 61)
idCompoundScoreTop Affiliating Genes
1egcg4410.4PRKAB1
2pge24410.3JUNB
3resveratrol44 59 11 2413.2PRKAB1
4cocl24410.0VHL, HIF1A
5cobalt chloride449.9HIF1A, VHL
6fumarate44 1110.8VHL, FH, HIF1A
7alpha-ketoglutarate449.8HIF1A, FH, VHL
8succinate449.8HIF1A, FH, VHL
9sch 39166449.7JUNB, FOS
10sunitinib44 49 1111.7VHL, HIF1A
11tamoxifen44 49 28 1112.7JUNB, FOS
12sch 23390449.7JUNB, FOS
13dizocilpine449.6FOS, JUNB
14superoxide44 2410.6SRF, FH
15geldanamycin44 49 59 1112.6TP53, HIF1A, VHL
16hpvs449.6TP53, JUNB
17pdtc449.4TP53, HIF1A, FOS
18sp 60012544 5910.4TP53, HIF1A, FOS
19capsaicin44 2810.4HIF1A, PRKAB1, FOS
202-deoxyglucose44 1110.4FOS, PRKAB1, HIF1A
21pyruvate449.2LDHA, HIF1A, PRKAB1, FH
22arsenite44 2410.2FOS, HIF1A, TP53
23pilocarpine44 28 1111.2SRF, FOS
24carbachol44 28 1111.0JUNB, FOS, PRKAB1
25n acetylcysteine448.9FOS, PRKAB1, HIF1A, TP53
26serine448.7VHL, FOS, PRKAB1, SRF
275fluorouracil448.7TP53, SRF, HIF1A
28ly294002448.7VHL, FOS, PRKAB1, HIF1A, TP53
29nadph44 249.7PRKAB1, HIF1A, SRF, LDHA
30actinomycin d448.6TP53, HIF1A, FOS, VHL, JUNB
31glucose448.5JUNB, PRKAB1, HIF1A, SRF
32proline448.5VHL, FH, HIF1A, SRF, TP53
33thymidine44 249.5TP53, SRF, HIF1A, FOS
34lactate448.4FH, PRKAB1, HIF1A, SRF, LDHA
35agar448.4FOS, HIF1A, SRF
36ionomycin448.4JUNB, FOS, PRKAB1, SRF
37sb 20358044 599.4JUNB, FOS, PRKAB1, HIF1A, TP53
38nitric oxide44 11 2410.4VHL, PRKAB1, HIF1A, SRF, LDHA
39h2o2448.3JUNB, FOS, PRKAB1, HIF1A, TP53
40dexamethasone44 49 28 1111.1SRF, HIF1A, FOS, JUNB
41oxygen44 249.1VHL, FH, PRKAB1, HIF1A, SRF, LDHA
42leucine448.0LDHA, SRF, PRKAB1, FOS, JUNB
43genistein44 28 59 2 11 2413.0SRF, HIF1A, PRKAB1, FOS, JUNB
44retinoic acid44 248.9JUNB, FOS, HIF1A, SRF, TP53
45threonine447.9JUNB, FOS, PRKAB1, HIF1A, SRF
46atp44 288.8JUNB, FH, PRKAB1, HIF1A, SRF, LDHA
47oligonucleotide447.7JUNB, VHL, FOS, HIF1A, SRF, TP53
48phosphatidylinositol447.7JUNB, VHL, FOS, PRKAB1, HIF1A, SRF
49vegf447.5TP53, VHL, FOS, PRKAB1, HIF1A, SRF
50tyrosine447.0JUNB, VHL, FH, FOS, PRKAB1, HIF1A

GO Terms for genes affiliated with Fumarate Hydratase Deficiency

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16Gene Ontology
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Cellular components related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1cytosolGO:0058297.8FOS, PRKAB1, HIF1A, LDHA, TP53, VHL
2nucleoplasmGO:0056547.8TP53, HIF1A, FOS, VHL, JUNB

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

(show all 17)
idNameGO IDScoreTop Affiliating Genes
1cellular response to extracellular stimulusGO:0316689.8FOS, LDHA
2regulation of transcription from RNA polymerase II promoter in response to hypoxiaGO:0614189.6HIF1A, VHL
3response to light stimulusGO:0094169.6JUNB, FOS
4cellular response to hypoxiaGO:0714569.5VHL, HIF1A, TP53
5mRNA transcription from RNA polymerase II promoterGO:0427899.5HIF1A, SRF
6response to corticosterone stimulusGO:0514129.4FOS, JUNB
7cellular response to hormone stimulusGO:0328709.4JUNB, FOS
8muscle cell cellular homeostasisGO:0467169.4SRF, HIF1A
9response to progesterone stimulusGO:0325709.3FOS, JUNB
10response to cAMPGO:0515919.3FOS, JUNB
11trophectodermal cell differentiationGO:0018299.2JUNB, SRF
12transforming growth factor beta receptor signaling pathwayGO:0071799.1TP53, FOS, JUNB
13cellular response to calcium ionGO:0712779.0FOS, JUNB
14positive regulation of cell differentiationGO:0455979.0SRF, VHL, JUNB
15positive regulation of transcription, DNA-dependentGO:0458939.0VHL, FOS, HIF1A, TP53
16response to cytokine stimulusGO:0340978.8SRF, FOS, JUNB
17positive regulation of transcription from RNA polymerase II promoterGO:0459447.9JUNB, FOS, HIF1A, SRF, TP53

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

(show all 10)
idNameGO IDScoreTop Affiliating Genes
1histone acetyltransferase bindingGO:0350359.7HIF1A, TP53
2RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positiGO:0012289.4SRF, TP53
3RNA polymerase II transcription factor binding transcription factor activityGO:0010769.4SRF, HIF1A
4protein kinase bindingGO:0199019.1TP53, HIF1A, PRKAB1
5RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positiveGO:0010779.0TP53, SRF, HIF1A
6transcription regulatory region DNA bindingGO:0442129.0FOS, HIF1A, TP53
7enzyme bindingGO:0198999.0TP53, HIF1A, VHL
8transcription factor bindingGO:0081348.1TP53, SRF, HIF1A, FOS, VHL
9sequence-specific DNA binding transcription factor activityGO:0037007.8TP53, SRF, HIF1A, FOS, JUNB
10protein bindingGO:0055156.4JUNB, VHL, FOS, PRKAB1, HIF1A, SRF

Products for genes affiliated with Fumarate Hydratase Deficiency

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Sources for Fumarate Hydratase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet