MCID: FMR011
MIFTS: 34

Fumarate Hydratase Deficiency malady

Categories: Genetic diseases

Aliases & Classifications for Fumarate Hydratase Deficiency

Aliases & Descriptions for Fumarate Hydratase Deficiency:

Name: Fumarate Hydratase Deficiency 23 24
Fumarase Deficiency 23 24 69
Fumaric Aciduria 23 24 69
Autosomal Recessive Fumarate Hydratase Deficiency 24
Fumarate Hydratase 13

Classifications:



Summaries for Fumarate Hydratase Deficiency

MalaCards based summary : Fumarate Hydratase Deficiency, also known as fumarase deficiency, is related to fumarase deficiency and renal cell carcinoma, and has symptoms including seizures An important gene associated with Fumarate Hydratase Deficiency is FH (Fumarate Hydratase), and among its related pathways/superpathways are ERK Signaling and Development HGF signaling pathway. The drugs Paclitaxel and Miconazole have been mentioned in the context of this disorder. Affiliated tissues include kidney, and related phenotypes are Decreased shRNA abundance (Z-score < -2) and cellular

GeneReviews: NBK1506

Related Diseases for Fumarate Hydratase Deficiency

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



Diseases related to Fumarate Hydratase Deficiency

Symptoms & Phenotypes for Fumarate Hydratase Deficiency

UMLS symptoms related to Fumarate Hydratase Deficiency:


seizures

GenomeRNAi Phenotypes related to Fumarate Hydratase Deficiency according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-144 9.4 VHL
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 9.4 HIF1A JUNB
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.4 JUNB
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.4 JUNB
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 9.4 HIF1A JUNB VHL
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 9.4 HIF1A
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.4 JUNB
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.4 JUNB
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 9.4 HIF1A

MGI Mouse Phenotypes related to Fumarate Hydratase Deficiency:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.95 FH FOS HIF1A JUNB SRF VHL
2 homeostasis/metabolism MP:0005376 9.88 FH FOS HIF1A JUNB SRF VHL
3 hematopoietic system MP:0005397 9.83 FOS HIF1A JUNB SRF VHL
4 immune system MP:0005387 9.77 FOS HIF1A JUNB SRF VHL
5 craniofacial MP:0005382 9.76 VHL FOS HIF1A SRF
6 mortality/aging MP:0010768 9.73 FH FOS HIF1A JUNB SRF VHL
7 limbs/digits/tail MP:0005371 9.62 FOS HIF1A JUNB VHL
8 neoplasm MP:0002006 9.46 FOS HIF1A JUNB VHL
9 renal/urinary system MP:0005367 9.26 FH HIF1A JUNB VHL
10 skeleton MP:0005390 9.02 FOS HIF1A JUNB SRF VHL

Drugs & Therapeutics for Fumarate Hydratase Deficiency

Drugs for Fumarate Hydratase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paclitaxel Approved, Vet_approved Phase 1 33069-62-4 36314
2
Miconazole Approved, Investigational, Vet_approved Phase 1 22916-47-8 4189
3
Everolimus Approved Phase 1 159351-69-6 6442177
4
Sirolimus Approved, Investigational Phase 1 53123-88-9 5284616 6436030 46835353
5
Docetaxel Approved May 1996, Investigational Phase 1 114977-28-5 148124 9877265
6 Albumin-Bound Paclitaxel Phase 1
7 Anti-Bacterial Agents Phase 1
8 Anti-Infective Agents Phase 1
9 Immunosuppressive Agents Phase 1
10 Antifungal Agents Phase 1
11 Antibiotics, Antitubercular Phase 1
12 Antimitotic Agents Phase 1
13 Antineoplastic Agents, Phytogenic Phase 1
14 glutamine Nutraceutical Phase 1

Interventional clinical trials:


id Name Status NCT ID Phase
1 Study of the Glutaminase Inhibitor CB-839 in Solid Tumors Recruiting NCT02071862 Phase 1

Search NIH Clinical Center for Fumarate Hydratase Deficiency

Genetic Tests for Fumarate Hydratase Deficiency

Genetic tests related to Fumarate Hydratase Deficiency:

id Genetic test Affiliating Genes
1 Fumarate Hydratase Deficiency 24 FH

Anatomical Context for Fumarate Hydratase Deficiency

MalaCards organs/tissues related to Fumarate Hydratase Deficiency:

39
Kidney

Publications for Fumarate Hydratase Deficiency

Articles related to Fumarate Hydratase Deficiency:

(show all 22)
id Title Authors Year
1
Fumarate Hydratase-deficient Uterine Leiomyomas Occur in Both the Syndromic and Sporadic Settings. ( 26574848 )
2016
2
Tubulocystic Carcinoma of the Kidney With Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-deficient Renal Cell Carcinoma. ( 27635946 )
2016
3
Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome. ( 26900816 )
2016
4
Fumarate Hydratase-deficient Cell Line NCCFH1 as a New In Vitro Model of Hereditary Papillary Renal Cell Carcinoma Type 2. ( 26637880 )
2015
5
Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency. ( 23499446 )
2013
6
Molecular pathways: Fumarate hydratase-deficient kidney cancer--targeting the Warburg effect in cancer. ( 23633457 )
2013
7
A novel fumarate hydratase-deficient HLRCC kidney cancer cell line, UOK268: a model of the Warburg effect in cancer. ( 22867999 )
2012
8
The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels. ( 21907923 )
2011
9
Structural basis of fumarate hydratase deficiency. ( 21445611 )
2011
10
Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis. ( 20978192 )
2010
11
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
12
Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism. ( 20660115 )
2010
13
Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas. ( 19151755 )
2009
14
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
15
Fumarate hydratase deficiency and cancer: activation of hypoxia signaling? ( 17418405 )
2007
16
Distinct expression profile in fumarate-hydratase-deficient uterine fibroids. ( 16319128 )
2006
17
Fumarate hydratase deficiency in monozygotic twins. ( 16876016 )
2006
18
Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. ( 12761039 )
2003
19
Fumarate hydratase deficiency: increased fumaric acid in amniotic fluid of two affected pregnancies. ( 11117439 )
2000
20
Fumarate hydratase deficiency. ( 9700607 )
1998
21
Fumarate Hydratase Deficiency ( 20301679 )
1993
22
Variability of clinical presentation in fumarate hydratase deficiency. ( 1432428 )
1992

Variations for Fumarate Hydratase Deficiency

ClinVar genetic disease variations for Fumarate Hydratase Deficiency:

6 (show all 22)
id Gene Variation Type Significance SNP ID Assembly Location
1 FH NM_000143.3(FH): c.793G> A (p.Ala265Thr) single nucleotide variant Pathogenic rs387906545 GRCh37 Chromosome 1, 241669414: 241669414
2 FH NM_000143.3(FH): c.1084G> C (p.Glu362Gln) single nucleotide variant Pathogenic rs121913119 GRCh37 Chromosome 1, 241667366: 241667366
3 FH NM_000143.3(FH): c.698G> A (p.Arg233His) single nucleotide variant Pathogenic rs121913123 GRCh37 Chromosome 1, 241671943: 241671943
4 FH FH, DEL deletion Pathogenic
5 FH NM_000143.3(FH): c.1255T> C (p.Ser419Pro) single nucleotide variant Pathogenic/Likely pathogenic rs200004220 GRCh37 Chromosome 1, 241663872: 241663872
6 FH NM_000143.3(FH): c.1293delA (p.Glu432Lysfs) deletion Pathogenic rs398123163 GRCh37 Chromosome 1, 241663834: 241663834
7 FH NM_000143.3(FH): c.912_918delTTTTGTC (p.Phe305Leufs) deletion Pathogenic rs794727836 GRCh37 Chromosome 1, 241667532: 241667538
8 FH NM_000143.3(FH): c.1430_1437dupAAAATGGA (p.Ser480Lysfs) duplication Pathogenic rs863223994 GRCh37 Chromosome 1, 241661224: 241661231
9 FH NM_000143.3(FH): c.1370_1371insTCAC (p.Ala458Hisfs) insertion Pathogenic/Likely pathogenic rs863223992 GRCh38 Chromosome 1, 241500456: 241500457
10 FH NM_000143.3(FH): c.1189G> A (p.Gly397Arg) single nucleotide variant Pathogenic rs863224007 GRCh38 Chromosome 1, 241502490: 241502490
11 FH NM_000143.3(FH): c.1097G> A (p.Ser366Asn) single nucleotide variant Pathogenic/Likely pathogenic rs863224004 GRCh37 Chromosome 1, 241667353: 241667353
12 FH NM_000143.3(FH): c.1083_1086delTGAA (p.Glu362Glnfs) deletion Pathogenic rs756469140 GRCh37 Chromosome 1, 241667364: 241667367
13 FH NM_000143.3(FH): c.267+1G> C single nucleotide variant Pathogenic rs878853691 GRCh37 Chromosome 1, 241680481: 241680481
14 FH NC_000001.11: g.(?_241497557)_(241504245_?)del deletion Pathogenic GRCh37 Chromosome 1, 241660857: 241667545
15 FH NC_000001.11: g.(?_241497557)_(241519785_?)del deletion Pathogenic GRCh38 Chromosome 1, 241497557: 241519785
16 FH NM_000143.3(FH): c.1112delA (p.Lys371Argfs) deletion Pathogenic rs1060500904 GRCh38 Chromosome 1, 241502567: 241502567
17 FH NM_000143.3(FH): c.1052C> A (p.Ser351Ter) single nucleotide variant Pathogenic rs1060500896 GRCh38 Chromosome 1, 241504098: 241504098
18 FH NM_000143.3(FH): c.267+1G> A single nucleotide variant Pathogenic rs878853691 GRCh38 Chromosome 1, 241517181: 241517181
19 FH NM_000143.3(FH): c.679C> T (p.Gln227Ter) single nucleotide variant Pathogenic rs11545658 GRCh38 Chromosome 1, 241508662: 241508662
20 FH NM_000143.3(FH): c.204T> A (p.Tyr68Ter) single nucleotide variant Pathogenic rs1060500883 GRCh38 Chromosome 1, 241517245: 241517245
21 FH NM_000143.3(FH): c.1347delG (p.Met449Ilefs) deletion Pathogenic rs1060500903 GRCh38 Chromosome 1, 241500480: 241500480
22 FH NM_000143.3(FH): c.560C> A (p.Ser187Ter) single nucleotide variant Pathogenic rs398123166 GRCh38 Chromosome 1, 241508781: 241508781

Expression for Fumarate Hydratase Deficiency

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

Pathways for Fumarate Hydratase Deficiency

Pathways related to Fumarate Hydratase Deficiency according to GeneCards Suite gene sharing:

(show all 29)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.48 FOS HIF1A JUNB SRF VHL
2
Show member pathways
12.25 FH FOS HIF1A VHL
3
Show member pathways
11.84 FOS HIF1A JUNB
4 11.64 HIF1A VHL
5 11.61 FOS JUNB
6
Show member pathways
11.6 HIF1A VHL
7
Show member pathways
11.56 FOS JUNB
8 11.55 FOS JUNB
9
Show member pathways
11.55 FOS JUNB
10 11.52 FH FOS HIF1A VHL
11
Show member pathways
11.49 FOS JUNB
12
Show member pathways
11.44 FOS HIF1A
13 11.4 FOS HIF1A
14 11.39 FOS HIF1A JUNB
15
Show member pathways
11.37 FOS JUNB
16 11.32 FOS JUNB
17 11.3 HIF1A VHL
18 11.27 FOS JUNB
19
Show member pathways
11.25 FOS SRF
20 11.18 FOS JUNB
21 11.17 FOS JUNB SRF
22 11.12 FOS SRF
23 11.01 FOS SRF
24 10.97 FOS JUNB
25
Show member pathways
10.95 FOS SRF
26
Show member pathways
10.94 FOS JUNB
27
Show member pathways
10.91 FOS HIF1A
28 10.71 FOS SRF
29 10.5 HIF1A VHL

GO Terms for Fumarate Hydratase Deficiency

Cellular components related to Fumarate Hydratase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.55 FOS HIF1A JUNB SRF VHL
2 transcription factor complex GO:0005667 9.13 FOS HIF1A JUNB
3 transcription factor AP-1 complex GO:0035976 8.62 FOS JUNB

Biological processes related to Fumarate Hydratase Deficiency according to GeneCards Suite gene sharing:

(show all 16)
id Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.92 FOS HIF1A JUNB SRF VHL
2 positive regulation of transcription from RNA polymerase II promoter GO:0045944 9.76 FOS HIF1A JUNB SRF
3 positive regulation of transcription, DNA-templated GO:0045893 9.67 FOS HIF1A SRF VHL
4 transcription from RNA polymerase II promoter GO:0006366 9.62 FOS HIF1A JUNB SRF
5 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0061418 9.56 HIF1A VHL
6 response to mechanical stimulus GO:0009612 9.55 FOS JUNB
7 heart looping GO:0001947 9.54 HIF1A SRF
8 cellular response to calcium ion GO:0071277 9.51 FOS JUNB
9 cellular response to hormone stimulus GO:0032870 9.49 FOS JUNB
10 response to cAMP GO:0051591 9.48 FOS JUNB
11 muscle cell cellular homeostasis GO:0046716 9.43 HIF1A SRF
12 mRNA transcription from RNA polymerase II promoter GO:0042789 9.4 HIF1A SRF
13 response to cytokine GO:0034097 9.33 FOS JUNB SRF
14 trophectodermal cell differentiation GO:0001829 9.26 JUNB SRF
15 positive regulation of cell differentiation GO:0045597 9.13 JUNB SRF VHL
16 positive regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1902895 8.8 FOS HIF1A SRF

Molecular functions related to Fumarate Hydratase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 transcription factor activity, sequence-specific DNA binding GO:0003700 9.62 FOS HIF1A JUNB SRF
2 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000978 9.54 FOS JUNB SRF
3 sequence-specific DNA binding GO:0043565 9.46 FOS HIF1A JUNB SRF
4 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0003705 9.4 HIF1A SRF
5 transcription factor activity, RNA polymerase II transcription factor binding GO:0001076 9.26 HIF1A SRF
6 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001077 9.26 FOS HIF1A JUNB SRF
7 transcription factor binding GO:0008134 9.02 FOS HIF1A JUNB SRF VHL

Sources for Fumarate Hydratase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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