MCID: FMR011
MIFTS: 50

Fumarate Hydratase Deficiency malady

Neuronal, Metabolic categories

Summaries for Fumarate Hydratase Deficiency

Sources:
43NIH Rare Diseases, 21Genetics Home Reference, 64Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
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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 hypoxia and uterine fibroid. 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 spleen, brain and liver, and related mouse phenotypes are limbs/digits/tail and embryogenesis.

NIH Rare Diseases:43 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:64 Fumarase deficiency (or fumaric aciduria), also known as \"Polygamist Down\'s\", is an autosomal... more...

Description from OMIM:47 606812

GeneReviews summary for fum

Aliases & Classifications for Fumarate Hydratase Deficiency

Sources:
19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 49Orphanet, 61UMLS, 22GTR, 47OMIM, 45Novoseek, 36MESH via Orphanet, 26ICD10 via Orphanet, 58SNOMED-CT via Orphanet, 62UMLS via Orphanet
See all sources

Classifications:

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


Characteristics (Orphanet epidemiological data):

49
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 43 20 21
fumarase deficiency 19 43 22 21 47 45 49 61
fumaric aciduria 19 43 21 49 61


External Ids:

OMIM47 606812
MESH via Orphanet36 C538191
ICD10 via Orphanet26 E88.8
SNOMED-CT via Orphanet58 124616002, 237983002
UMLS via Orphanet62 C0342770, C2936826

Related Diseases for Fumarate Hydratase Deficiency

Sources:
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
1hypoxia10.5
2uterine fibroid10.3
3biliary atresia10.1
4polyhydramnios10.1
5encephalomyopathy10.1
6hypotonia10.1
7leiomyoma10.0FH
8leiomyoma, uterine, somatic10.0FH
9cystadenoma10.0VHL
10peutz-jeghers syndrome10.0VHL
11hemangioma10.0VHL
12primary hyperoxaluria10.0FOS
13neuroblastoma10.0TP53
14multiple myeloma10.0TP53
15colon adenocarcinoma10.0FOS
16thyroid cancer10.0TP53
17esophageal cancer10.0TP53
18leiomyomatosis10.0VHL, FH
19sarcoma10.0TP53
20hereditary leiomyomatosis and renal cell cancer10.0FH, HIF1A
21obesity10.0PRKAB1, HIF1A
22osteoarthritis10.0JUNB
23familial colorectal cancer10.0FH, VHL
24hemangioblastoma10.0HIF1A, VHL
25cystic kidney10.0VHL, FH
26von hippel-lindau disease10.0HIF1A, VHL
27hyperglycemia10.0PRKAB1, HIF1A
28gastric ulcer10.0SRF
29insulin resistance10.0FOS, PRKAB1
30psoriasis10.0JUNB
31tuberous sclerosis10.0VHL, PRKAB1
32multiple sclerosis10.0SRF
33fibrosarcoma10.0FOS, HIF1A
34oral cancer10.0TP53, HIF1A
35erythrocytosis10.0HIF1A, VHL
36endometriosis10.0SRF
37fibrous dysplasia10.0FOS
38myeloid leukemia10.0FOS, JUNB
39kidney rhabdoid cancer10.0FH, VHL, HIF1A
40renal clear cell carcinoma10.0HIF1A, FH, VHL
41paraganglioma10.0FH, HIF1A, VHL
42oxyphilic adenoma10.0VHL, FH
43atherosclerosis10.0SRF, PRKAB1
44pancreatic cancer10.0HIF1A, TP53
45bladder carcinoma10.0FH, TP53
46deficiency anemia10.0SRF, HIF1A
47ischemia10.0HIF1A, JUNB, PRKAB1
48asthma10.0FOS, SRF
49vascular disease10.0FOS, TP53, HIF1A
50endometrial carcinoma10.0HIF1A, TP53, FOS

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



Diseases related to fumarate hydratase deficiency

Clinical Features for Fumarate Hydratase Deficiency

Sources:
47OMIM
See all sources

Clinical features from OMIM:

606812

Clinical synopsis from OMIM:

606812

Drugs & Therapeutics for Fumarate Hydratase Deficiency

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials, 61UMLS, 41NDF-RT
See all sources

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

Sources:
20GeneTests, 22GTR
See all sources

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

Sources:
33MalaCards
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MalaCards organs/tissues related to Fumarate Hydratase Deficiency:

33
Spleen, Brain, Liver

Animal Models for Fumarate Hydratase Deficiency or affiliated genes

Sources:
37MGI, 28inGenious Targeting Laboratory
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Publications for Fumarate Hydratase Deficiency

Sources:
51PubMed
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Articles related to Fumarate Hydratase Deficiency:

(show all 14)
idTitleAuthorsYear
1
Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency. (23499446)
2013
2
Cutaneous and uterine leiomyomatosis and ovarian cystadenoma associated with deficiency of fumarate hydratase. (24396716)
2011
3
Structural basis of fumarate hydratase deficiency. (21445611)
2011
4
Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis. (20978192)
2010
5
Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas. (19151755)
2009
6
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
7
The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. (18366737)
2008
8
Fumarate hydratase deficiency and cancer: activation of hypoxia signaling? (17418405)
2007
9
Fumarate hydratase deficiency in monozygotic twins. (16876016)
2006
10
Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. (12761039)
2003
11
Fumarate hydratase deficiency: increased fumaric acid in amniotic fluid of two affected pregnancies. (11117439)
2000
12
Fumarate hydratase deficiency. (9700607)
1998
13
Fumarate Hydratase Deficiency (20301679)
1993
14
Variability of clinical presentation in fumarate hydratase deficiency. (1432428)
1992

Genetic Variations for Fumarate Hydratase Deficiency

Sources:
63UniProtKB/Swiss-Prot
See all sources

Genetic disease variations for Fumarate Hydratase Deficiency:

63
id Symbol AA change Variation SNP ID
1FHp.Lys230ArgVAR_002445
2FHp.Ala308ThrVAR_002446
3FHp.Phe312CysVAR_002447
4FHp.Asp425ValVAR_002448

Expression for genes affiliated with Fumarate Hydratase Deficiency

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
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

Sources:
54Reactome, 38NCBI BioSystems Database, 12EMD Millipore, 30KEGG, 4Cell Signaling Technology, 52QIAGEN, 53R&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
9.7HIF1A, VHL
29.7SRF
3
Development Leptin signaling via JAK/STAT and MAPK cascades
Hide members
9.5FOS, HIF1A
49.3VHL, HIF1A, LDHA
59.3FOS, JUNB
69.3FOS, JUNB
79.3VHL, HIF1A, TP53
89.3LDHA, PRKAB1, FH
99.2LDHA, HIF1A, FOS
109.1SRF, FOS
11
Immune response IL-6 signaling pathway
Hide members
9.1FOS, SRF
129.1SRF, FOS
138.9VHL, HIF1A, LDHA, TP53
14
Hide members
8.9TP53, FOS, JUNB
15
G-protein signaling Ras family GTPases in kinase cascades (scheme)
Hide members
8.9TP53, FOS, JUNB
16
Hide members
8.8JUNB, FOS, PRKAB1
17
Hide members
8.8FH, PRKAB1, LDHA, TP53
188.7TP53, SRF, FOS
19
Hide members
8.7TP53, SRF, FOS
208.5SRF, FOS, JUNB
21
Hide members
8.5SRF, FOS, JUNB
228.4VHL, FH, FOS, HIF1A, TP53
23
Translation Insulin regulation of translation
Hide members
8.4JUNB, FOS, PRKAB1, HIF1A
24
Hide members
7.6TP53, SRF, HIF1A, FOS, FH, VHL
25
Hide members
6.8JUNB, VHL, FOS, PRKAB1, HIF1A, SRF

Compounds for genes affiliated with Fumarate Hydratase Deficiency

Sources:
45Novoseek, 60Tocris Bioscience, 11DrugBank, 24HMDB, 50PharmGKB, 29IUPHAR, 2BitterDB
See all sources

Compounds related to Fumarate Hydratase Deficiency according to GeneCards/GeneDecks:

(show top 50)    (show all 61)
idCompoundScoreTop Affiliating Genes
1egcg4510.4PRKAB1
2pge24510.3JUNB
3resveratrol45 60 11 2413.2PRKAB1
4cocl24510.0VHL, HIF1A
5cobalt chloride459.9HIF1A, VHL
6fumarate45 1110.8VHL, FH, HIF1A
7alpha-ketoglutarate459.8HIF1A, FH, VHL
8succinate459.8HIF1A, FH, VHL
9sch 39166459.7JUNB, FOS
10sunitinib45 50 1111.7VHL, HIF1A
11tamoxifen45 50 29 1112.7JUNB, FOS
12sch 23390459.7JUNB, FOS
13dizocilpine459.6FOS, JUNB
14superoxide45 2410.6SRF, FH
15geldanamycin45 50 60 1112.6TP53, HIF1A, VHL
16hpvs459.6TP53, JUNB
17pdtc459.4TP53, HIF1A, FOS
18sp 60012545 6010.4TP53, HIF1A, FOS
19capsaicin45 2910.4HIF1A, PRKAB1, FOS
202-deoxyglucose45 1110.4FOS, PRKAB1, HIF1A
21pyruvate459.2LDHA, HIF1A, PRKAB1, FH
22arsenite45 2410.2FOS, HIF1A, TP53
23pilocarpine45 29 1111.2SRF, FOS
24carbachol45 29 1111.0JUNB, FOS, PRKAB1
25n acetylcysteine458.9FOS, PRKAB1, HIF1A, TP53
26serine458.7VHL, FOS, PRKAB1, SRF
275fluorouracil458.7TP53, SRF, HIF1A
28ly294002458.7VHL, FOS, PRKAB1, HIF1A, TP53
29nadph45 249.7PRKAB1, HIF1A, SRF, LDHA
30actinomycin d458.6TP53, HIF1A, FOS, VHL, JUNB
31glucose458.5JUNB, PRKAB1, HIF1A, SRF
32proline458.5VHL, FH, HIF1A, SRF, TP53
33thymidine45 249.5TP53, SRF, HIF1A, FOS
34lactate458.4FH, PRKAB1, HIF1A, SRF, LDHA
35agar458.4FOS, HIF1A, SRF
36ionomycin458.4JUNB, FOS, PRKAB1, SRF
37sb 20358045 609.4JUNB, FOS, PRKAB1, HIF1A, TP53
38nitric oxide45 11 2410.4VHL, PRKAB1, HIF1A, SRF, LDHA
39h2o2458.3JUNB, FOS, PRKAB1, HIF1A, TP53
40dexamethasone45 50 29 1111.1SRF, HIF1A, FOS, JUNB
41oxygen45 249.1VHL, FH, PRKAB1, HIF1A, SRF, LDHA
42leucine458.0LDHA, SRF, PRKAB1, FOS, JUNB
43genistein45 29 60 2 11 2413.0SRF, HIF1A, PRKAB1, FOS, JUNB
44retinoic acid45 248.9JUNB, FOS, HIF1A, SRF, TP53
45threonine457.9JUNB, FOS, PRKAB1, HIF1A, SRF
46atp45 298.8JUNB, FH, PRKAB1, HIF1A, SRF, LDHA
47oligonucleotide457.7JUNB, VHL, FOS, HIF1A, SRF, TP53
48phosphatidylinositol457.7JUNB, VHL, FOS, PRKAB1, HIF1A, SRF
49vegf457.5TP53, VHL, FOS, PRKAB1, HIF1A, SRF
50tyrosine457.0JUNB, VHL, FH, FOS, PRKAB1, HIF1A

GO Terms for genes affiliated with Fumarate Hydratase Deficiency

Sources:
16Gene Ontology
See all sources

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:0316689.8LDHA, FOS
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:0514129.4JUNB, FOS
7cellular response to hormone stimulusGO:0328709.4FOS, JUNB
8muscle cell cellular homeostasisGO:0467169.4HIF1A, SRF
9response to progesterone stimulusGO:0325709.3FOS, JUNB
10response to cAMPGO:0515919.3JUNB, FOS
11trophectodermal cell differentiationGO:0018299.2SRF, JUNB
12transforming growth factor beta receptor signaling pathwayGO:0071799.1TP53, FOS, JUNB
13cellular response to calcium ionGO:0712779.0FOS, JUNB
14positive regulation of cell differentiationGO:0455979.0JUNB, VHL, SRF
15positive regulation of transcription, DNA-dependentGO:0458939.0FOS, HIF1A, TP53, VHL
16response to cytokine stimulusGO:0340978.8JUNB, SRF, FOS
17positive regulation of transcription from RNA polymerase II promoterGO:0459447.9HIF1A, TP53, SRF, FOS, JUNB

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:0010769.4HIF1A, SRF
4protein kinase bindingGO:0199019.1HIF1A, PRKAB1, TP53
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:0442129.0HIF1A, TP53, FOS
7enzyme bindingGO:0198999.0VHL, HIF1A, TP53
8transcription factor bindingGO:0081348.1TP53, SRF, VHL, FOS, HIF1A
9sequence-specific DNA binding transcription factor activityGO:0037007.8JUNB, FOS, HIF1A, SRF, TP53
10protein bindingGO:0055156.4JUNB, VHL, FOS, PRKAB1, HIF1A, SRF

Products for genes affiliated with Fumarate Hydratase Deficiency

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  • Lysates
  • Antibodies

Sources for Fumarate Hydratase Deficiency

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet