FH (fumarate hydratase)

Gene

• Entrez ID: 2271
• Gene name: Fumarate hydratase
• Gene symbol: FH
• Synonyms (NCBI Gene): FMRD, HLRCC, HsFH, LRCC, MCL, MCUL1
• Chromosome: 1
• Chromosome location: 1q43
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2070080	G>A,T	Benign, likely-pathogenic	Stop gained, coding sequence variant, synonymous variant
rs11545654	C>T	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs11545655	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant
rs11545658	G>A	Pathogenic	Stop gained, coding sequence variant
rs61736558	C>A	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs75086406	C>G,T	Uncertain-significance, pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs121913119	C>G	Pathogenic	Missense variant, coding sequence variant
rs121913120	G>A	Pathogenic	Stop gained, coding sequence variant
rs121913121	T>G	Pathogenic-likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs121913122	G>A	Pathogenic	Stop gained, coding sequence variant
rs121913123	C>A,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs144131869	GAGAGAGAGAGAGAGAGA>-,GA,GAGA,GAGAGA,GAGAGAGA,GAGAGAGAGA,GAGAGAGAGAGA,GAGAGAGAGAGAGA,GAGAGAGAGAGAGAGA,GAGAGAGAGAGAGAGAGAGA,GAGAGAGAGAGAGAGAGAGAGA,GAGAGAGAGAGAGAGAGAGAGAGA,GAGAGAGAGAGAGAGAGAGAGAGAGA,GAGAGAGAGAGAGAGAGAGAGAGAGAGA,GAGAGAGAGAGAGAGAGAGAGAGAGAGAG	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Intron variant
rs145116688	T>A,C	Likely-pathogenic, uncertain-significance	Coding sequence variant, 5 prime UTR variant, missense variant
rs199822819	G>C,T	Pathogenic, uncertain-significance, pathogenic-likely-pathogenic	Missense variant, coding sequence variant
rs199971078	G>A,C	Pathogenic, benign, uncertain-significance, likely-benign	Upstream transcript variant, coding sequence variant, stop gained, synonymous variant, genic upstream transcript variant
rs200004220	A>G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs200496951	G>A,C	Pathogenic, uncertain-significance	Stop gained, missense variant, coding sequence variant, 5 prime UTR variant
rs200796606	T>G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs201395553	C>A,G	Uncertain-significance, likely-pathogenic, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs202166344	G>A,C	Pathogenic, uncertain-significance	Upstream transcript variant, genic upstream transcript variant, missense variant, coding sequence variant, stop gained
rs367543046	->TTT	Likely-pathogenic, pathogenic-likely-pathogenic, conflicting-interpretations-of-pathogenicity	Coding sequence variant, inframe insertion
rs369802820	G>A,C	Uncertain-significance, conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant
rs372505976	T>C,G	Pathogenic, uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs376260223	G>A	Conflicting-interpretations-of-pathogenicity	Intron variant
rs387906545	C>T	Pathogenic	Coding sequence variant, missense variant
rs398123159	A>T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs398123160	G>A	Pathogenic	Coding sequence variant, stop gained
rs398123162	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs398123163	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs398123164	C>T	Pathogenic, likely-pathogenic, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs398123165	CTTT>-	Pathogenic	Coding sequence variant, frameshift variant
rs398123166	G>A,C,T	Pathogenic, likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant, stop gained
rs398123167	G>A	Pathogenic	Coding sequence variant, stop gained
rs398123168	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs587781682	G>A,C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs587782207	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, 5 prime UTR variant
rs587782216	T>C,G	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs587782618	C>T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs727503926	G>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs727503927	A>T	Likely-pathogenic, pathogenic	Stop gained, coding sequence variant
rs727503928	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs750273092	T>A,C	Pathogenic, likely-pathogenic	Splice acceptor variant
rs750447792	T>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs752232718	T>C	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs755436052	G>A	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs756469140	CATT>-	Pathogenic	Frameshift variant, coding sequence variant
rs768182640	->CA	Pathogenic	Coding sequence variant, frameshift variant
rs772190176	C>T	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs776190273	T>-	Likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant
rs776313200	T>A,C,G	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs776806414	T>A,C,G	Likely-pathogenic, uncertain-significance	Initiator codon variant, missense variant, upstream transcript variant, genic upstream transcript variant
rs779707997	T>C,G	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs780001199	CT>-	Pathogenic	Coding sequence variant, frameshift variant
rs781466938	T>-,TT	Pathogenic	Coding sequence variant, frameshift variant, stop gained
rs786202220	GCATGGCAGCTTTTATTCTTG>-	Pathogenic, likely-pathogenic	Coding sequence variant, inframe deletion
rs786202907	GCA>-	Likely-pathogenic, uncertain-significance	Coding sequence variant, inframe deletion
rs794727698	C>G	Pathogenic	Splice acceptor variant
rs794727836	ACAAAAG>-	Pathogenic	Coding sequence variant, frameshift variant
rs797044973	C>G,T	Pathogenic, likely-pathogenic	Splice acceptor variant
rs797044974	C>A	Pathogenic	Coding sequence variant, stop gained
rs863223965	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs863223966	T>C	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs863223968	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs863223972	A>C	Likely-pathogenic	Missense variant, coding sequence variant
rs863223973	A>C,G	Likely-benign, likely-pathogenic	Missense variant, coding sequence variant, synonymous variant
rs863223977	T>A	Pathogenic	Coding sequence variant, stop gained
rs863223978	C>G,T	Pathogenic, likely-pathogenic, uncertain-significance	Splice acceptor variant
rs863223979	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs863223980	G>A	Pathogenic	Coding sequence variant, stop gained, 5 prime UTR variant
rs863223981	->A	Pathogenic	Coding sequence variant, frameshift variant
rs863223982	C>T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant, 5 prime UTR variant
rs863223984	->GCTTTTATTCTTGTCATTGCA	Likely-pathogenic	Inframe insertion, coding sequence variant
rs863223985	CAGCAGTGCCTCCAGCTGCGA>-	Pathogenic	Coding sequence variant, inframe deletion
rs863223987	GGC>AGT	Likely-pathogenic	Missense variant, coding sequence variant
rs863223988	GTCA>-	Pathogenic	Coding sequence variant, frameshift variant
rs863223989	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs863223990	TCAT>-,TCATTCAT	Pathogenic	Inframe insertion, coding sequence variant, frameshift variant, stop gained
rs863223991	GA>-	Pathogenic	Coding sequence variant, frameshift variant
rs863223992	->GAGT	Pathogenic	Coding sequence variant, frameshift variant
rs863223993	->T	Pathogenic	Coding sequence variant, frameshift variant
rs863223994	->CCATTTTT	Pathogenic	Coding sequence variant, frameshift variant
rs863223995	ATTTA>-	Pathogenic	Coding sequence variant, stop gained
rs863223998	G>A	Pathogenic	Coding sequence variant, stop gained
rs863224000	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs863224001	C>A,T	Pathogenic, likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, stop gained
rs863224002	G>T	Likely-pathogenic	Missense variant, coding sequence variant
rs863224003	A>C	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs863224004	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs863224006	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs863224007	C>T	Pathogenic	Missense variant, coding sequence variant
rs863224008	T>A	Pathogenic	Splice acceptor variant
rs863224009	A>C	Likely-pathogenic	Missense variant, coding sequence variant
rs863224010	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs863224011	C>T	Pathogenic	Splice acceptor variant
rs863224013	C>A,T	Pathogenic	Missense variant, coding sequence variant, stop gained, 5 prime UTR variant
rs863224015	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs863224016	->A	Pathogenic	Coding sequence variant, frameshift variant
rs863224017	CTTCAAG>-	Pathogenic	Coding sequence variant, frameshift variant
rs876658569	C>-	Pathogenic	Coding sequence variant, stop gained
rs876660446	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs878853691	C>G,T	Pathogenic	Splice donor variant
rs878853694	T>C	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs886039363	C>G	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs886039364	TT>-	Pathogenic	Frameshift variant, coding sequence variant
rs886039365	T>C	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs886039367	C>A	Pathogenic, likely-pathogenic	Splice donor variant
rs886039368	C>T	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained
rs886041201	GA>-	Pathogenic	Frameshift variant, coding sequence variant
rs886042044	CA>-	Pathogenic	Frameshift variant, coding sequence variant
rs1031919395	A>C,T	Pathogenic, uncertain-significance	5 prime UTR variant, stop gained, coding sequence variant
rs1057517734	C>A	Likely-pathogenic, pathogenic	Splice donor variant
rs1057521425	C>A,T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1057524385	G>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1060499629	CCACTTACTG>-	Pathogenic	Splice donor variant, intron variant, coding sequence variant
rs1060499630	G>A	Likely-pathogenic, pathogenic	Stop gained, coding sequence variant
rs1060499631	A>-	Pathogenic	Stop gained, coding sequence variant
rs1060499633	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1060499634	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060499635	TGCTGT>-	Likely-pathogenic, pathogenic	Inframe deletion, coding sequence variant
rs1060499636	A>C,G	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1060499637	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060499638	C>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1060499639	C>G,T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1060499641	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060499642	C>A	Pathogenic	Stop gained, coding sequence variant
rs1060499643	T>A,C	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1060499644	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060499645	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1060500883	A>T	Pathogenic	Stop gained, 5 prime UTR variant, coding sequence variant
rs1060500896	G>A,C,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs1060500900	->G	Uncertain-significance, pathogenic	5 prime UTR variant, coding sequence variant, frameshift variant
rs1060500901	A>G	Pathogenic-likely-pathogenic	Splice donor variant
rs1060500902	C>T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1060500903	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060500904	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060500907	CTGCT>-	Pathogenic	Coding sequence variant, frameshift variant
rs1064792900	TACCTGCCCAAGAGTAAGTG>-	Pathogenic	Splice donor variant, intron variant, coding sequence variant
rs1064793125	T>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1064793126	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1064793741	T>C	Pathogenic	Splice acceptor variant
rs1064795320	T>-	Likely-pathogenic	Splice acceptor variant
rs1064796708	A>C	Likely-pathogenic, pathogenic	Stop gained, coding sequence variant
rs1131691234	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1131691235	CT>-	Pathogenic	Coding sequence variant, splice acceptor variant
rs1131691237	G>-	Pathogenic	5 prime UTR variant, coding sequence variant, frameshift variant
rs1131691238	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1131691239	G>A	Pathogenic	Stop gained, coding sequence variant
rs1131691240	T>C	Pathogenic	Splice acceptor variant
rs1131691241	A>G	Likely-pathogenic	Splice donor variant
rs1131691243	C>A	Pathogenic	Stop gained, coding sequence variant
rs1131691244	G>A	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1131691245	G>C	Pathogenic	Stop gained, coding sequence variant
rs1131691246	->TTCA	Pathogenic	Stop gained, 5 prime UTR variant, coding sequence variant
rs1131691248	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1131691249	C>G,T	Likely-pathogenic, pathogenic	Splice donor variant
rs1131691622	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1158759883	T>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs1355199594	G>A,C	Uncertain-significance, pathogenic	Missense variant, stop gained, coding sequence variant
rs1375252870	C>G,T	Likely-pathogenic	Splice donor variant
rs1439046582	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1553340506	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1553340681	->GTTGATCCTTTCTGTATTGGCCTGGATTCCCACCACGCAGTTT	Pathogenic	Coding sequence variant, frameshift variant
rs1553340686	->ATCCTTTCTGTATTGGCCTGGATTCCCACCACGCAGTTTTCTG	Pathogenic	Coding sequence variant, frameshift variant
rs1553340687	C>A	Pathogenic	Stop gained, coding sequence variant
rs1553340708	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1553340709	A>C	Likely-pathogenic	Stop gained, coding sequence variant
rs1553341012	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1553341026	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1553341031	G>T	Pathogenic	Stop gained, coding sequence variant
rs1553341034	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1553341046	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1553341049	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1553341148	C>T	Likely-pathogenic	Splice donor variant
rs1553341163	TA>-	Likely-pathogenic	Stop gained, coding sequence variant
rs1553341174	T>C,G	Likely-pathogenic	Splice acceptor variant
rs1553341337	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1553341345	A>C,G	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1553341353	G>A	Pathogenic	Stop gained, coding sequence variant
rs1553341367	GT>-	Pathogenic	Coding sequence variant, frameshift variant
rs1553341582	C>G	Likely-pathogenic	Intron variant
rs1553341610	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1553341623	C>T	Pathogenic	Splice acceptor variant
rs1553341942	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1553341945	->A	Pathogenic	Stop gained, coding sequence variant
rs1553341951	->C	Pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant
rs1553342155	G>AT	Likely-pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant
rs1558396285	A>G	Likely-pathogenic	Splice donor variant
rs1558396320	C>A	Pathogenic	Stop gained, coding sequence variant
rs1558397011	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1558400571	G>A	Pathogenic	Stop gained, coding sequence variant
rs1558401064	T>-	Pathogenic	Frameshift variant, coding sequence variant
rs1558401094	TTACTTCAGCGGCCGCTCG>-	Pathogenic	Frameshift variant, coding sequence variant
rs1558402241	A>C,T	Pathogenic	Stop gained, 5 prime UTR variant, coding sequence variant
rs1558402255	->GGCA	Pathogenic	Frameshift variant, 5 prime UTR variant, coding sequence variant
rs1573876584	C>A	Pathogenic	Coding sequence variant, stop gained
rs1573878004	->TTCT	Pathogenic	Coding sequence variant, frameshift variant
rs1573878071	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1573878145	T>A	Pathogenic	Coding sequence variant, stop gained
rs1573878149	C>A	Likely-pathogenic	Splice acceptor variant
rs1573879289	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1573879313	GTTCCCCATG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1573881533	ACTAACCTGTAAGTGCAGC>-	Pathogenic	Splice donor variant, intron variant, coding sequence variant
rs1573881629	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1573881633	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1573883195	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1573883310	TGCATTGCTGTGGGAAAAGTATCA>C	Pathogenic	Coding sequence variant, frameshift variant
rs1573883342	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1573885482	G>C	Pathogenic	Coding sequence variant, stop gained
rs1573885503	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1573885519	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1573886367	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1573886415	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1573886490	TAA>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs1573888356	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs1573888513	C>A	Pathogenic	Coding sequence variant, stop gained, 5 prime UTR variant
rs1573888556	AATTTTGG>-	Pathogenic	Coding sequence variant, 5 prime UTR variant, frameshift variant
rs1573889860	AGCCGCGTTCG>-	Pathogenic	Coding sequence variant, 5 prime UTR variant, frameshift variant
rs1573890070	->T	Pathogenic	Coding sequence variant, stop gained, genic upstream transcript variant, upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT047393	hsa-miR-34a-5p	CLASH	23622248
MIRT030090	hsa-miR-26b-5p	Luciferase reporter assay, qRT-PCR, Western blot	26078955
MIRT996331	hsa-miR-4708-5p	CLIP-seq
MIRT996332	hsa-miR-4720-3p	CLIP-seq
MIRT996333	hsa-miR-4804-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000050	Process	Urea cycle	IEA
GO:0000050	Process	Urea cycle	ISS
GO:0000050	Process	Urea cycle	ISS
GO:0000821	Process	Regulation of arginine metabolic process	ISS
GO:0003824	Function	Catalytic activity	IEA
GO:0004333	Function	Fumarate hydratase activity	IBA
GO:0004333	Function	Fumarate hydratase activity	IDA	26237645, 30718813, 30761759
GO:0004333	Function	Fumarate hydratase activity	IEA
GO:0004333	Function	Fumarate hydratase activity	IMP	29456767
GO:0004333	Function	Fumarate hydratase activity	TAS	3828494
GO:0005515	Function	Protein binding	IPI	25416956, 26237645, 32296183, 39251607
GO:0005634	Component	Nucleus	IDA	20231875, 26237645
GO:0005634	Component	Nucleus	IEA
GO:0005694	Component	Chromosome	IEA
GO:0005737	Component	Cytoplasm	IDA	27037871
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	8200987
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	27037871
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	TAS	8200987
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IDA	20231875
GO:0005829	Component	Cytosol	IEA
GO:0006099	Process	Tricarboxylic acid cycle	IBA
GO:0006099	Process	Tricarboxylic acid cycle	IEA
GO:0006106	Process	Fumarate metabolic process	IBA
GO:0006106	Process	Fumarate metabolic process	IDA	26237645, 30718813, 30761759
GO:0006106	Process	Fumarate metabolic process	IEA
GO:0006106	Process	Fumarate metabolic process	TAS	8200987
GO:0006108	Process	Malate metabolic process	IBA
GO:0006108	Process	Malate metabolic process	IDA	30761759
GO:0006281	Process	DNA repair	IEA
GO:0006525	Process	Arginine metabolic process	IEA
GO:0006525	Process	Arginine metabolic process	ISS
GO:0006974	Process	DNA damage response	IDA	20231875, 26237645
GO:0006974	Process	DNA damage response	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0035861	Component	Site of double-strand break	IDA	26237645
GO:0042393	Function	Histone binding	IPI	26237645
GO:0048873	Process	Homeostasis of number of cells within a tissue	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	IEA
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	27554470
GO:2001034	Process	Positive regulation of double-strand break repair via nonhomologous end joining	IDA	26237645

Other IDs

• MIM: 136850
• HGNC: 3700
• e!Ensembl: ENSG00000091483

Protein

• UniProt ID: P07954
• Protein name: Fumarate hydratase, mitochondrial (Fumarase) (HsFH) (EC 4.2.1.2)
• Protein function: Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:30761759). Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the oth
• PDB: 3E04, 5D6B, 5UPP, 6EBT, 6V8F, 6VBE, 7LUB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00206	Lyase_1	58 → 389	Lyase	Domain
  PF10415	FumaraseC_C	455 → 508	Fumarase C C-terminus	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in red blood cells; underexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology. {ECO:0000269|PubMed:22509282}.
• Sequence:

  MYRALRLLARSRPLVRAPAAALASAPGLGGAAVPSFWPPNAARMASQNSFRIEYDTFGEL
  KVPNDKYYGAQTVRSTMNFKIGGVTERMPTPVIKAFGILKRAAAEVNQDYGLDPKIANAI
  MKAADEVAEGKLNDHFPLVVWQTGSGTQTNMNVNEVISNRAIEMLGGELGSKIPVHPNDH
  VNKSQSSNDTFPTAMHIAAAIEVHEVLLPGLQKLHDALDAKSKEFAQIIKIGRTHTQDAV
  PLTLGQEFSGYVQQVKYAMTRIKAAMPRIYELAAGGTAVGTGLNTRIGFAEKVAAKVAAL
  TGLPFVTAPNKFEALAAHDALVELSGAMNTTACSLMKIANDIRFLGSGPRSGLGELILPE
  NEPGSSIMPGKVNPTQCEAMTMVAAQVMGNHVAVTVGGSNGHFELNVFKPMMIKNVLHSA
  RLLGDASVSFTENCVVGIQANTERINKLMNESLMLVTALNPHIGYDKAAKIAKTAHKNGS
  TLKETAIELGYLTAEQFDEWVKPKDMLGPK

• Sequence length: 510

Pathways

KEGG:

Citrate cycle (TCA cycle)
Pyruvate metabolism
Metabolic pathways
Carbon metabolism
Cushing syndrome
Pathways in cancer
Renal cell carcinoma

Reactome:

Citric acid cycle (TCA cycle)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cutaneous leiomyoma	Likely pathogenic; Pathogenic	rs763390436, rs1060499630	RCV005420449 RCV000626620	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial cancer of breast	Likely pathogenic	rs2147913449	RCV005930174	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
FH-related disorder	Likely pathogenic; Pathogenic	rs1057517734, rs199822819, rs398123159, rs200004220	RCV003335313 RCV003335052 RCV004555535 RCV004555536	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Fumarase deficiency	Likely pathogenic; Pathogenic	rs1448268784, rs2147913041, rs587781682, rs587782618, rs786202220, rs372505976, rs863223978, rs794727836, rs797044973, rs863224008, rs863223992, rs863224007, rs863224004, rs756469140, rs1553341148, rs886039367, rs886039364, rs886039362, rs886041201, rs2527332585, rs2527308382, rs2527335176, rs2527345537, rs2527322866, rs1226883651, rs1659988368, rs1060500900, rs387906545, rs121913119, rs121913120, rs121913122, rs121913123, rs2527313050, rs1060499644, rs768182640, rs1553341942, rs199822819, rs1060500901, rs1064796708, rs776190273, rs752232718, rs1131691248, rs1553341582, rs1375252870, rs1553341364, rs1553341012, rs1573879313, rs976734433, rs1553341174, rs1660143675, rs398123159, rs200004220, rs398123163, rs121913121, rs398123168	RCV001775239 RCV004556087 RCV000549060 RCV004567146 RCV003462155 RCV002498811 RCV003465720 RCV003462288 RCV000804152 RCV004567400 RCV004567403 RCV003462309 RCV000465210 RCV004567402 RCV003462308 RCV002503771 RCV001251427 RCV003469195 RCV001062945 RCV004567819 RCV003466053 RCV003468193 RCV003461569 RCV003461570 RCV003468195 RCV003461572 RCV005254845 RCV005014932 RCV000017617 RCV000017618 RCV000515176 RCV003466863 RCV000178717 RCV004576602 RCV003463832 RCV003470388 RCV003463831 RCV000022554 RCV000458630 RCV003464036 RCV003464027 RCV003464063 RCV003470611 RCV005018836 RCV003464109 RCV004800449 RCV000635303 RCV000810743 RCV000797723 RCV002495120 RCV003469407 RCV003460741 RCV005394337 RCV000461548 RCV005016360 RCV000762893	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hereditary cancer	Likely pathogenic	rs1573880531	RCV004698852	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary cancer-predisposing syndrome	Pathogenic; Likely pathogenic	rs2147917609, rs2147919711, rs2147911365, rs2147916281, rs2147911550, rs2147913407, rs2147921876, rs2147911225, rs2147913368, rs976734433, rs587781682, rs587782216, rs587782618, rs2147919608, rs2527332795, rs2527332897, rs1660103724, rs2147914878, rs2527327569, rs2527332504, rs2527332427, rs2527332379, rs2527327168, rs1659989676, rs786202220, rs372505976, rs786202833, rs2527319814, rs2527319648, rs2527316491, rs2527323113, rs1573881633, rs2527344866, rs2527313025, rs2527308607, rs2527308386, rs863223978, rs2527308315, rs2527319143, rs1060500883, rs2147925168, rs2527335338, rs1660148115, rs794727836, rs797044974, rs797044973, rs863223993, rs863224010, rs863224008, rs863223992, rs863223977, rs1553340687, rs863224009, rs863224007, rs863224004, rs863223966, rs756469140, rs863224016, rs863223973, rs863223972, rs863224002, rs863224001, rs863224000, rs1553341148, rs863223981, rs863223968, rs863223967, rs863223965, rs779707997, rs863224015, rs863223983, rs863223995, rs863224017, rs863223980, rs863223982, rs1060499642, rs2527332608, rs1659988368, rs876660446, rs876658569, rs878853694, rs878853691, rs1307815197, rs863224003, rs886039368, rs886039367, rs886039366, rs886039365, rs886039364, rs886039363, rs886039362, rs886041201, rs2527319050, rs1553341582, rs2527316769, rs2527340288, rs2527340320, rs2527322866, rs2527308465, rs2527319019, rs199909758, rs121913119, rs121913120, rs121913122, rs121913123, rs75086406, rs1417243893, rs2527327592, rs1231254705, rs2527323022, rs1057517734, rs1060499645, rs1060499644, rs781466938, rs1060499641, rs1064792900, rs1060499635, rs398123166, rs750273092, rs768182640, rs1060499629, rs1553341942, rs863224013, rs199822819, rs1060500896, rs11545655, rs1060500901, rs750447792, rs11545658, rs1060500903, rs1060499639, rs1064796708, rs1553340686, rs1064793125, rs776190273, rs1131691245, rs863223990, rs1131691244, rs1131691249, rs1131691238, rs1131691234, rs1131691239, rs1131691243, rs752232718, rs1131691248, rs1131691235, rs1131691242, rs1131691240, rs1131691241, rs1131691246, rs1131691237, rs1375252870, rs1553340884, rs1553341353, rs1553341623, rs1553341364, rs1553341945, rs1553341031, rs1553341367, rs1553341012, rs1553341037, rs1553341049, rs1558401064, rs1558401094, rs1558402241, rs776313200, rs1558400571, rs1573876584, rs1355199594, rs1573888513, rs1553341174, rs1573888556, rs1573878071, rs1573878145, rs1439046582, rs1573883195, rs1553341345, rs1573883342, rs1573885482, rs1573885503, rs1573886367, rs1573886490, rs1573888356, rs1573878149, rs1553341046, rs1659924638, rs1659990191, rs1659746788, rs1659745968, rs1659922131, rs1659853029, rs1660143675, rs398123159, rs398123160, rs200004220, rs398123163, rs121913121, rs398123167, rs398123168, rs1659806431	RCV002432063 RCV004619680 RCV005831887 RCV003298632 RCV002388587 RCV002361050 RCV002334696 RCV005841872 RCV002388932 RCV002398014 RCV000129845 RCV000130899 RCV000131997 RCV002271334 RCV002328188 RCV002355388 RCV002355544 RCV002351475 RCV002347351 RCV002340950 RCV002351765 RCV002351929 RCV002378000 RCV002367462 RCV000164936 RCV000163828 RCV000165850 RCV002430238 RCV002378559 RCV002374307 RCV002364897 RCV002364901 RCV002396318 RCV002414353 RCV002383292 RCV002387257 RCV002391649 RCV002397173 RCV002396686 RCV002392369 RCV002410554 RCV002421802 RCV002425833 RCV002439225 RCV002435338 RCV001018881 RCV005841527 RCV000493531 RCV005338106 RCV002390521 RCV000494502 RCV000494183 RCV000493806 RCV004619226 RCV001010667 RCV002336534 RCV001017278 RCV000220270 RCV000493004 RCV000494113 RCV000493972 RCV000493913 RCV000494152 RCV002372179 RCV000493445 RCV002372178 RCV004020396 RCV002257492 RCV004948207 RCV002354552 RCV000494490 RCV000493387 RCV002327040 RCV004020397 RCV002286713 RCV000494159 RCV000561722 RCV005565334 RCV004617155 RCV005343589 RCV000222416 RCV000213630 RCV001023046 RCV002429090 RCV003177559 RCV003219455 RCV000494499 RCV001011336 RCV002347970 RCV000492991 RCV005338120 RCV001020456 RCV002429193 RCV000494455 RCV003278317 RCV003278318 RCV005335754 RCV003339129 RCV003339137 RCV005834508 RCV005335821 RCV004950486 RCV006382058 RCV004950541 RCV002426509 RCV000130873 RCV000130875 RCV000493379 RCV002362588 RCV002433458 RCV004520598 RCV004520603 RCV004520610 RCV004520614 RCV001017339 RCV002393069 RCV001010289 RCV002323668 RCV000575212 RCV001026175 RCV005831603 RCV000563738 RCV000492920 RCV002348253 RCV000572356 RCV005831602 RCV000493657 RCV002402222 RCV000492836 RCV002402239 RCV006386837 RCV003278809 RCV002429484 RCV000562894 RCV005562361 RCV000493845 RCV003338596 RCV005831607 RCV003168979 RCV004023175 RCV002350049 RCV001023474 RCV000493518 RCV000494640 RCV000494270 RCV000493187 RCV000493020 RCV000494465 RCV000493233 RCV000493068 RCV000493486 RCV000494410 RCV000494308 RCV000493280 RCV000493891 RCV000493792 RCV000493124 RCV000494321 RCV000494432 RCV005338213 RCV004023829 RCV005338230 RCV004023831 RCV003380603 RCV002358480 RCV000568960 RCV000567476 RCV002386006 RCV001024403 RCV004948493 RCV002386007 RCV004948494 RCV006386956 RCV001020556 RCV001018055 RCV004025153 RCV002422551 RCV001019860 RCV005841621 RCV005338388 RCV005562462 RCV003380736 RCV005562461 RCV005562474 RCV005831747 RCV001010580 RCV001010521 RCV001018919 RCV001025872 RCV001025484 RCV001025388 RCV001024493 RCV001022335 RCV001022160 RCV001021145 RCV001016588 RCV001015542 RCV001014112 RCV001010486 RCV002281646 RCV002445265 RCV002409418 RCV002365686 RCV002355081 RCV002379848 RCV002393506 RCV004951363 RCV002429988 RCV002339690 RCV003339546 RCV002366032 RCV000220396 RCV002444546 RCV000492881 RCV000493624 RCV000493777 RCV001024322 RCV005831550 RCV002371923 RCV004619615	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hereditary leiomyomatosis and renal cell cancer	Likely pathogenic; Pathogenic	rs2147919711, rs863224000, rs2147917619, rs2147911225, rs587781682, rs587782618, rs2147916319, rs2147913449, rs1157768121, rs2527313198, rs727503927, rs1659989676, rs786202220, rs372505976, rs786202833, rs2527319814, rs2527319221, rs794727836, rs797044974, rs797044973, rs863223993, rs863224010, rs863223992, rs863224007, rs863224004, rs863223966, rs756469140, rs863224016, rs863224002, rs863224001, rs1553341148, rs863223965, rs779707997, rs863223995, rs863223980, rs863224011, rs878853695, rs878853691, rs886039368, rs886039367, rs886039366, rs886039365, rs886039364, rs886039363, rs886041201, rs2527319645, rs2527316769, rs2527332585, rs2527340288, rs2527316491, rs2527308398, rs2527327500, rs2527332814, rs2527340210, rs2527335224, rs1060500900, rs121913120, rs780001199, rs121913122, rs121913123, rs75086406, rs2527308519, rs1057517734, rs1060499645, rs1553340681, rs1060499644, rs781466938, rs1060499642, rs1060499641, rs1060499637, rs1064792900, rs863223968, rs1060499635, rs398123166, rs750273092, rs768182640, rs1060499634, rs1060499633, rs1060499631, rs1060499630, rs1060499629, rs1553341942, rs863224013, rs199822819, rs863223978, rs750447792, rs1060500883, rs1060499639, rs1064796708, rs1553340686, rs776190273, rs1131691245, rs1131691240, rs1131691241, rs1553341582, rs1553341163, rs1553341337, rs1553341031, rs1553341037, rs1558401064, rs1558401094, rs1558402241, rs776313200, rs1553341174, rs1573878145, rs1439046582, rs1573885482, rs1573881533, rs121913119, rs1553341623, rs1660242061, rs1659922131, rs1659988368, rs1660143675, rs398123159, rs398123160, rs200004220, rs398123163, rs121913121, rs398123168	RCV005237764 RCV004699136 RCV005421050 RCV003456252 RCV005620906 RCV001029752 RCV002254382 RCV002266555 RCV002289038 RCV002292257 RCV000190645 RCV003138224 RCV003456005 RCV003316008 RCV003454408 RCV003456287 RCV002466957 RCV000179717 RCV000192733 RCV000193655 RCV005620913 RCV000445635 RCV004791319 RCV000445595 RCV002291591 RCV000445606 RCV000445586 RCV002288799 RCV003454493 RCV003483571 RCV005237696 RCV002503771 RCV002222438 RCV000445603 RCV000445600 RCV000445602 RCV000445590 RCV005425868 RCV000445634 RCV000445633 RCV003454775 RCV006268700 RCV003456042 RCV003456041 RCV003456040 RCV003335299 RCV003230783 RCV003316944 RCV003316968 RCV005249505 RCV003450108 RCV003450150 RCV003456333 RCV003450155 RCV003450609 RCV005871223 RCV005014932 RCV000017619 RCV000017621 RCV000017622 RCV000017623 RCV000017624 RCV000017625 RCV004589318 RCV003456067 RCV000445610 RCV000445609 RCV000445613 RCV000445607 RCV000445617 RCV000445598 RCV000445636 RCV000445593 RCV000445621 RCV000445627 RCV000445604 RCV000445615 RCV000445584 RCV000445619 RCV000445601 RCV000445618 RCV000445632 RCV000445611 RCV000445591 RCV000445623 RCV003483435 RCV004791467 RCV004022582 RCV004017625 RCV003449126 RCV005869462 RCV005600952 RCV003139683 RCV004023169 RCV005869513 RCV005869512 RCV005600956 RCV005018836 RCV003139736 RCV005422819 RCV004791651 RCV003451511 RCV004026458 RCV003336138 RCV003316800 RCV005414266 RCV001563611 RCV002282425 RCV005871122 RCV006249700 RCV001027656 RCV003455187 RCV004030597 RCV001201265 RCV005252118 RCV003142196 RCV003336355 RCV005253754 RCV000445596 RCV000445587 RCV000445624 RCV000445588 RCV000017620 RCV000445585 RCV000445608	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Inherited phaeochromocytoma and paraganglioma excluding NF1	Likely pathogenic; Pathogenic	rs863224000	RCV005865271	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian serous cystadenocarcinoma	Pathogenic; Likely pathogenic	rs863223998, rs1659988368, rs1573878149	RCV005893495 RCV005926824 RCV005912378	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spinocerebellar ataxia 45	Pathogenic	rs121913123	RCV004541007	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Uterine corpus endometrial carcinoma	Pathogenic	rs1131691243	RCV005899777	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Uterine leiomyoma	Likely pathogenic; Pathogenic	rs1060499630	RCV000626620	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
B Lymphoblastic Leukemia/Lymphoma, Not Otherwise Specified	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatoblastoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Inherited renal cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIOMYOSARCOMA	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PHEOCHROMOCYTOMA-PARAGANGLIOMA	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations