FH

Protein identityUniProt · HPA

UniProt accession

P07954

Gene

FH

Ensembl

ENSG00000091483

Chromosome

1

Canonical length

510 aa

Protein class

Cancer-related genes, Citric acid cycle related proteins, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

510 residues, UniProt reviewed canonical sequence.

>P07954|FH
     1  MYRALRLLAR SRPLVRAPAA ALASAPGLGG AAVPSFWPPN AARMASQNSF RIEYDTFGEL
    61  KVPNDKYYGA QTVRSTMNFK IGGVTERMPT PVIKAFGILK RAAAEVNQDY GLDPKIANAI
   121  MKAADEVAEG KLNDHFPLVV WQTGSGTQTN MNVNEVISNR AIEMLGGELG SKIPVHPNDH
   181  VNKSQSSNDT FPTAMHIAAA IEVHEVLLPG LQKLHDALDA KSKEFAQIIK IGRTHTQDAV
   241  PLTLGQEFSG YVQQVKYAMT RIKAAMPRIY ELAAGGTAVG TGLNTRIGFA EKVAAKVAAL
   301  TGLPFVTAPN KFEALAAHDA LVELSGAMNT TACSLMKIAN DIRFLGSGPR SGLGELILPE
   361  NEPGSSIMPG KVNPTQCEAM TMVAAQVMGN HVAVTVGGSN GHFELNVFKP MMIKNVLHSA
   421  RLLGDASVSF TENCVVGIQA NTERINKLMN ESLMLVTALN PHIGYDKAAK IAKTAHKNGS
   481  TLKETAIELG YLTAEQFDEW VKPKDMLGPK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

253 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FH.

Disease | AllUniProt

Conditions FH is implicated in, by any mechanism.

• Fumarase deficiency (FMRD) MIM:606812

Disease | GeneticClinVar

501 pathogenic / likely-pathogenic of 2,515 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary cancer-predisposing syndrome
• Hereditary leiomyomatosis and renal cell cancer
• Fumarase deficiency
• FH-related disorder
• Ovarian serous cystadenocarcinoma

Disease | ImmuneIEDB

Conditions an epitope on FH was assayed in.

• brain glioma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.54

gnomAD pLI

0.09

gnomAD missense Z

1.27

DepMap mean gene effect

-0.21

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• arginine metabolic process
• DNA damage response
• DNA repair
• homeostasis of number of cells within a tissue
• malate metabolic process
• positive regulation of cold-induced thermogenesis
• positive regulation of double-strand break repair via nonhomologous end joining
• regulation of arginine metabolic process
• tricarboxylic acid cycle
• urea cycle
• fumarate metabolic process

Molecular functions

• histone binding
• fumarate hydratase activity

Cellular components

• chromosome
• cytoplasm
• cytosol
• extracellular exosome
• mitochondrial matrix
• mitochondrion
• nucleus
• site of double-strand break

Protein domainsUniProt · Pfam · InterPro

• Fumarate lyase family
• L-Aspartase-like
• Fumarate lyase, conserved site
• Fumarate lyase, N-terminal
• Fumarase/histidase, N-terminal
• Lyase
• Fumarate hydratase, class II
• Fumarase C, C-terminal
• Fumarase C C-terminus

KeywordsUniProt

• Acetylation
• Alternative initiation
• Chromosome
• Cytoplasm
• DNA damage
• DNA repair
• Lyase
• Mitochondrion
• Nucleus
• Phosphoprotein
• Transit peptide
• Tricarboxylic acid cycle
• Tumor suppressor

InteractionsUniProt · HPA

Protein binding partners of FH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• H2AZ1