EuRBPDB

Basic Information
Cancer Related Information

Description

RBPome

Expression

Transcripts

Gene Model

Pathways

PPI

Orthologs

Gene Ontology

Description

Ensembl ID: ENSG00000091483 (Gene tree)
Gene ID: 2271
Gene Symbol: FH
Alias: N
Full Name: fumarate hydratase
Gene Type: protein_coding
Species: Homo_sapiens
Status: putative
Strand: Minus strand
Length: 22,229 bases
Position: chr1:241,497,557-241,519,785
Accession: 3700
RBP type: non-canonical RBP
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. [provided by RefSeq, Jul 2008]

RNA binding proteome (RBPome)

PID	Title	Method	Time	Author	Doi
29431736	Capturing the interactome of newly transcribed RNA	PolyT-RICK & Hela	2018 Feb 12	Bao X	DOI: 10.1038/nmeth.4595
29431736	Capturing the interactome of newly transcribed RNA	RICK & Hela	2018 Feb 12	Bao X	DOI: 10.1038/nmeth.4595
30528433	The Human RNA-Binding Proteome and Its Dynamics during Translational Arrest	XRNAX & Hela	2018 Dec 6	Trendel J	DOI: 10.1016/j.cell.2018.11.004
30607034	Comprehensive identification of RNA protein interactions in any organism using orthogonal organic phase separation (OOPS)	OOPS & MCF10A	2019 Jan 3	Queiroz RML	DOI: 10.1038/s41587-018-0001-2

Expression

Transcripts

Transcript ID	Name	Length	RefSeq ID	Protein ID	Length	RefSeq ID	UniportKB ID
ENST00000493477	FH-202	414	-	-	- (aa)	-	-
ENST00000366560	FH-201	1797	XM_011544132	ENSP00000355518	510 (aa)	XP_011542434	P07954
ENST00000497042	FH-203	351	-	-	- (aa)	-	-

Gene Model

Click here to download ENSG00000091483's gene model file

Pathways

Pathway ID	Pathway Name	Source
hsa00020	Citrate cycle (TCA cycle)	KEGG
hsa00620	Pyruvate metabolism	KEGG
hsa01100	Metabolic pathways	KEGG
hsa01200	Carbon metabolism	KEGG
hsa04934	Cushing syndrome	KEGG
hsa05200	Pathways in cancer	KEGG
hsa05211	Renal cell carcinoma	KEGG

Protein-Protein Interaction (PPI)

Clik here to download ENSG00000091483's network

* RBP PPI network refers to all genes directly bind to RBP

Orthologs identified by RBPome

Ensembl ID	Gene Symbol	Coverage	Identiy	Ortholog	Gene Symbol	Coverage	Identiy	Species
ENSG00000091483	FH	99	72.222	WBGene00001503	fum-1	99	75.841	Caenorhabditis_elegans
ENSG00000091483	FH	94	66.597	YPL262W		98	66.597	Saccharomyces_cerevisiae

Gene Ontology

Go ID	Go_term	PubmedID	Evidence	Category
GO:0004333	fumarate hydratase activity	21873635.	IBA	Function
GO:0005515	protein binding	25416956.26237645.	IPI	Function
GO:0005737	cytoplasm	8200987.	TAS	Component
GO:0005739	mitochondrion	20833797.	HDA	Component
GO:0005739	mitochondrion	21873635.	IBA	Component
GO:0005739	mitochondrion	-	IDA	Component
GO:0005759	mitochondrial matrix	-	TAS	Component
GO:0006099	tricarboxylic acid cycle	21873635.	IBA	Process
GO:0006099	tricarboxylic acid cycle	-	IEA	Process
GO:0006099	tricarboxylic acid cycle	-	TAS	Process
GO:0006106	fumarate metabolic process	21873635.	IBA	Process
GO:0006108	malate metabolic process	21873635.	IBA	Process
GO:0045239	tricarboxylic acid cycle enzyme complex	-	IEA	Component
GO:0048873	homeostasis of number of cells within a tissue	-	IEA	Process
GO:0070062	extracellular exosome	20458337.	HDA	Component
GO:0120162	positive regulation of cold-induced thermogenesis	27554470.	ISS	Process

Cancer associated literatures

PID	Title	Article	Time	Author	Doi
28620008	PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood.	Clin Cancer Res	2017 Jun 15	Schultz KAP	doi: 10.1158/1078-0432.CCR-17-0629.
16237213	Missense mutations in fumarate hydratase in multiple cutaneous and uterine leiomyomatosis and renal cell cancer.	J Mol Diagn	2005 Oct	Alam NA	-
28260082	Cancer-associated fibroblasts enhance pancreatic cancer cell invasion by remodeling the metabolic conversion mechanism.	Oncol Rep	2017 Apr	Shan T	doi: 10.3892/or.2017.5479
17960613	mutation of the fumarase gene creates a dominant negative protein.	Int J Cancer	2008 Feb 15	Lorenzato A	-
19276158	LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer.	Mol Cancer Ther	2009 Mar	Xie H	doi: 10.1158/1535-7163.MCT-08-1049
22677546	Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors.	Genes Dev	2012 Jun 15	Xiao M	doi: 10.1101/gad.191056.112
16757530	Adult leydig cell tumors of the testis caused by germline fumarate hydratase mutations.	J Clin Endocrinol Metab	2006 Aug	Carvajal-Carmona LG	-
20231875	Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response.	PLoS Biol	2010 Mar 9	Yogev O	doi: 10.1371/journal.pbio.1000328.
27161211	Complete Penetrance and Absence of Intrafamilial Variability in a Large Family with Hereditary Leiomyomatosis and Renal Cell Carcinoma.	Dermatology	2016	Guinard E	doi: 10.1159/000445430
28628081	O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency.	Nat Cell Biol	2017 Jul	Wang T	doi: 10.1038/ncb3562
19963135	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.	Cancer Genet Cytogenet	2010 Jan 1	Yang Y	doi: 10.1016/j.cancergencyto.2009.08.018.
11865300	Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.	Nat Genet	2002 Apr	Tomlinson IP	-
16597677	Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.	J Med Genet	2006 Sep	Pithukpakorn M	-
23295344	Downregulation of fumarate hydratase is related to tumorigenesis in sporadic renal cell cancer.	Urol Int	2013	Ha YS	doi: 10.1159/000345608
26275867	Incidental diagnosis of HLRCC following investigation for Asperger Syndrome: actionable and actioned.	Fam Cancer	2016 Jan	Duong BT	doi: 10.1007/s10689-015-9829-5.
15937070	Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.	J Med Genet	2006 Jan	Wei MH	-
17908262	Evidence for a founder effect of the germline fumarate hydratase gene mutation R58P causing hereditary leiomyomatosis and renal cell cancer (HLRCC).	Ann Hum Genet	2008 Jan	Heinritz W	-
27097334	Loss of Fumarate Hydratase and Aberrant Protein Succination Detected With S-(2-Succino)-Cysteine Staining to Identify Patients With Multiple Cutaneous and Uterine Leiomyomatosis and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.	Am J Dermatopathol	2016 Dec	Llamas-Velasco M	-
26493120	Novel fumarate hydratase mutation in a family with atypical uterine leiomyomas and hereditary leiomyomatosis and renal cell cancer.	Fertil Steril	2016 Jan	Wheeler KC	doi: 10.1016/j.fertnstert.2015.09.034
16639410	Germline fumarate hydratase mutations in patients with ovarian mucinous cystadenoma.	Eur J Hum Genet	2006 Jul	Ylisaukko-oja SK	-
18986479	Absence of fumarate hydratase mutation in a family with cutaneous leiomyosarcoma and renal cancer.	Int J Dermatol	2008 Nov	Badeloe S	doi: 10.1111/j.1365-4632.2008.03952.x.
21398687	Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma.	J Med Genet	2011 Apr	Gardie B	doi: 10.1136/jmg.2010.085068
24684806	Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas.	BMC Res Notes	2014 Mar 31	Kuwada M	doi: 10.1186/1756-0500-7-203.
25923021	Fumarate Hydratase Mutation in a Young Woman With Uterine Leiomyomas and a Family History of Renal Cell Cancer.	Obstet Gynecol	2015 Jul	Mann ML	doi: 10.1097/AOG.0000000000000702.
28196407	Comprehensive genomic and phenotypic characterization of germline FH deletion in hereditary leiomyomatosis and renal cell carcinoma.	Genes Chromosomes Cancer	2017 Jun	Vocke CD	doi: 10.1002/gcc.22452
27528759	Isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), fumarate hydratase (FH): three players for one phenotype in cancer?	Biochem Soc Trans	2016 Aug 15	Laurenti G	doi: 10.1042/BST20160099.
27302170	Chromatin Remodeling Factor LSH Drives Cancer Progression by Suppressing the Activity of Fumarate Hydratase.	Cancer Res	2016 Oct 1	He X	-
27566483	Hereditary leiomyomatosis and renal cell cancer syndrome: identification and clinical characterization of a novel mutation in the FH gene in a Colombian family.	Fam Cancer	2017 Jan	Arenas Valencia C	doi: 10.1007/s10689-016-9922-4.
29917289	Fumarate hydratase inactivation in hereditary leiomyomatosis and renal cell cancer is synthetic lethal with ferroptosis induction.	Cancer Sci	2018 Sep	Kerins MJ	doi: 10.1111/cas.13701

Expression in 33 cancers

Mutations

Cancer	Chr	Position	Mutation Type	dbSNP	Protein-change	Allele Freq
BLCA	chr1	241500574	Missense_Mutation	novel	H418L	0.08
BLCA	chr1	241500571	Missense_Mutation	NA	S419L	0.65
BLCA	chr1	241513687	Missense_Mutation	novel	I98M	0.26
BLCA	chr1	241512035	Nonsense_Mutation	novel	E163*	0.43
BLCA	chr1	241504211	Missense_Mutation	novel	E313D	0.53
BLCA	chr1	241502491	Silent	NA	V396V	0.2
BLCA	chr1	241500470	Missense_Mutation	NA	L453V	0.65
BLCA	chr1	241517301	Missense_Mutation	NA	F50I	0.12
BRCA	chr1	241497683	3'UTR	novel		0.11
BRCA	chr1	241513636	Missense_Mutation	novel	K115N	0.06
BRCA	chr1	241506129	Missense_Mutation	novel	T260A	0.09
BRCA	chr1	241512080	Missense_Mutation	NA	Q148E	0.12
BRCA	chr1	241506059	Missense_Mutation	NA	L283S	0.31
BRCA	chr1	241517245	Nonsense_Mutation	NA	Y68*	0.19
CESC	chr1	241508716	Missense_Mutation	novel	P209S	0.09
CESC	chr1	241517222	Missense_Mutation	rs778578307	T76M	0.17
COAD	chr1	241513674	Missense_Mutation	novel	A103T	0.08
COAD	chr1	241500522	Silent	rs772415507	V435V	0.41
COAD	chr1	241508740	Missense_Mutation	novel	I201L	0.31
COAD	chr1	241504197	Missense_Mutation	rs755449276	H318R	0.16
COAD	chr1	241513675	Silent	rs142283468	A102A	0.2
COAD	chr1	241513622	Missense_Mutation	novel	I120K	0.27
GBM	chr1	241517242	Silent	novel	G69G	0.46
GBM	chr1	241500496	Missense_Mutation	novel	R444T	0.03
HNSC	chr1	241517311	Missense_Mutation	novel	S46R	0.22
HNSC	chr1	241506003	Missense_Mutation	novel	G302C	0.33
HNSC	chr1	241517234	Missense_Mutation	novel	T72S	0.09
KIRC	chr1	241497788	3'UTR	novel		0.18
KIRP	chr1	241497972	Splice_Site	novel	X464_splice	0.27
KIRP	chr1	241500512	Nonsense_Mutation	NA	Q439*	0.43
LGG	chr1	241504122	Missense_Mutation	rs756990249	R343Q	0.35
LIHC	chr1	241517250	Missense_Mutation	novel	Y67H	0.41
LIHC	chr1	241504142	Missense_Mutation	NA	M336I	0.52
LIHC	chr1	241504144	Missense_Mutation	NA	M336L	0.52
LUAD	chr1	241512124	Missense_Mutation	novel	N133S	0.05
LUAD	chr1	241502514	Missense_Mutation	NA	G389W	0.09
LUAD	chr1	241500556	Missense_Mutation	novel	G424V	0.17
LUAD	chr1	241517249	Missense_Mutation	novel	Y67S	0.08
LUAD	chr1	241506015	Missense_Mutation	rs201395553	A298S	0.21
LUAD	chr1	241508687	Silent	novel	L218L	0.09
LUAD	chr1	241506003	Missense_Mutation	rs200412958	G302S	0.17
LUAD	chr1	241504186	Missense_Mutation	novel	V322F	0.14
LUAD	chr1	241508765	Silent	novel	P192P	0.19
LUAD	chr1	241513712	Missense_Mutation	novel	T90I	0.14
LUAD	chr1	241504198	Missense_Mutation	rs398123168	H318Y	0.15
LUAD	chr1	241508620	Missense_Mutation	novel	P241A	0.07
LUAD	chr1	241502547	Nonsense_Mutation	NA	E378*	0.13
LUAD	chr1	241497952	Missense_Mutation	NA	K470R	0.13
LUAD	chr1	241513609	Silent	NA	A124A	0.06
LUAD	chr1	241512085	Frame_Shift_Del	novel	*G146Efs6**	0.09
LUSC	chr1	241497925	Missense_Mutation	novel	G479E	0.19
LUSC	chr1	241504098	Nonsense_Mutation	NA	S351*	0.38
LUSC	chr1	241506040	Silent	novel	F289F	0.27
LUSC	chr1	241513713	Nonsense_Mutation	novel	T90*	0.04
LUSC	chr1	241513685	Nonsense_Mutation	novel	L99*	0.06
LUSC	chr1	241506090	Missense_Mutation	novel	A273P	0.31
LUSC	chr1	241506022	Silent	rs199635833	A295A	0.36
LUSC	chr1	241513675	Silent	rs142283468	A102A	0.34
LUSC	chr1	241500581	Missense_Mutation	NA	V416L	0.39
LUSC	chr1	241506056	Missense_Mutation	novel	N284S	0.45
LUSC	chr1	241504187	Silent	novel	L321L	0.45
OV	chr1	241500502	Missense_Mutation	NA	T442R	0.2
PAAD	chr1	241508612	Silent	novel	T243T	0.5
PAAD	chr1	241513658	Missense_Mutation	novel	Q108R	0.26
PRAD	chr1	241506008	Missense_Mutation	NA	L300H	0.44
PRAD	chr1	241508632	Missense_Mutation	novel	Q237K	0.07
PRAD	chr1	241502475	Missense_Mutation	rs760360724	H402Y	0.27
READ	chr1	241502524	Silent	NA	A385A	0.12
READ	chr1	241506100	Silent	novel	I269I	0.41
READ	chr1	241512054	Silent	rs202061330	V156V	0.44
SKCM	chr1	241504225	Missense_Mutation	rs368849989	P309S	0.19
SKCM	chr1	241506001	Splice_Site	NA	X302_splice	0.13
SKCM	chr1	241517303	Missense_Mutation	NA	S49F	0.12
SKCM	chr1	241508728	Missense_Mutation	novel	E205Q	0.42
SKCM	chr1	241517303	Missense_Mutation	NA	S49F	0.29
SKCM	chr1	241513659	Missense_Mutation	novel	Q108E	0.38
SKCM	chr1	241497872	Missense_Mutation	NA	F497L	0.12
STAD	chr1	241517241	Missense_Mutation	rs587782207	A70T	0.27
STAD	chr1	241508768	Silent	NA	F191F	0.39
STAD	chr1	241517222	Missense_Mutation	rs778578307	T76M	0.17
STAD	chr1	241504167	Missense_Mutation	NA	M328T	0.15
STAD	chr1	241504075	Missense_Mutation	novel	P359A	0.32
THCA	chr1	241502551	Missense_Mutation	NA	Q376H	0.37
UCEC	chr1	241497792	3'UTR	novel		0.43
UCEC	chr1	241504123	Nonsense_Mutation	rs121913122	R343*	0.28
UCEC	chr1	241497816	3'UTR	novel		0.41
UCEC	chr1	241497837	Silent	novel	G508G	0.38
UCEC	chr1	241512021	Silent	NA	G167G	0.2
UCEC	chr1	241504192	Missense_Mutation	rs766441385	A320T	0.36
UCEC	chr1	241513671	Missense_Mutation	novel	A104T	0.14
UCEC	chr1	241502571	Splice_Site	novel	X370_splice	0.11
UCEC	chr1	241500590	Splice_Site	novel	X413_splice	0.08
UCEC	chr1	241504075	Missense_Mutation	novel	P359S	0.18
UCEC	chr1	241513692	Missense_Mutation	NA	G97S	0.23
UCEC	chr1	241506168	Nonsense_Mutation	novel	E247*	0.57
UCEC	chr1	241500591	Splice_Site	novel	X413_splice	0.47
UCEC	chr1	241497779	3'UTR	novel		0.43
UCEC	chr1	241497867	Silent	rs199949526	D498D	0.39
UCEC	chr1	241508637	Missense_Mutation	NA	H235R	0.39
UCEC	chr1	241500591	Splice_Site	novel	X413_splice	0.53
UCEC	chr1	241512120	Silent	novel	D134D	0.42
UCEC	chr1	241497899	Missense_Mutation	rs201115573	E488K	0.19
UCEC	chr1	241504122	Missense_Mutation	rs756990249	R343Q	0.28
UCEC	chr1	241497866	Missense_Mutation	rs750838853	E499K	0.32
UCEC	chr1	241497899	Missense_Mutation	rs201115573	E488K	0.33
UCEC	chr1	241512033	Silent	novel	E163E	0.34
UCEC	chr1	241504192	Missense_Mutation	rs766441385	A320T	0.13
UCEC	chr1	241517189	Missense_Mutation	rs200007371	R87H	0.14
UCEC	chr1	241502483	Missense_Mutation	NA	S399I	0.16
UCEC	chr1	241506057	Missense_Mutation	novel	N284H	0.32

Copy Number Variations (CNVs)

Cancer	Type	Freq	Q-value
BRCA	AMP	0.6898	1.4246e-20
DLBC	DEL	0.1458	0.0017831
KIRC	DEL	0.0682	0.018371
LGG	DEL	0.0351	0.11599
LIHC	AMP	0.6568	4.3428e-09
PCPG	DEL	0.0988	0.12617
READ	AMP	0.2667	0.14328
SARC	DEL	0.2879	2.6086e-08
TGCT	DEL	0.0133	0.16985
THYM	AMP	0.187	0.24554
UCEC	AMP	0.3729	2.3921e-06

Survival Analysis

Cancer	P-value	Q-value
KIRC	0.044	Kaplan-Meier Survival Analysis
SKCM	0.0013	Kaplan-Meier Survival Analysis
ESCA	0.02	Kaplan-Meier Survival Analysis
KIRP	0.0001	Kaplan-Meier Survival Analysis
COAD	0.0043	Kaplan-Meier Survival Analysis
LAML	0.00036	Kaplan-Meier Survival Analysis
OV	0.037	Kaplan-Meier Survival Analysis

Drugs

EuRBPDB

Description

RBPome

Expression

Transcripts

Gene Model

Pathways

PPI

Orthologs

Gene Ontology

Select Dataset :

Input Drug :

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Eesembl ID

Cell lines and drugs in GSE70138 or GSE92742