FECH

Protein identityUniProt · HPA

UniProt accession

P22830

Gene

FECH

Ensembl

ENSG00000066926

Chromosome

18

Canonical length

423 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Quaternary structure

Homotetramer

OverviewNCBI Gene

The protein encoded by this gene is localized to the mitochondrion, where it catalyzes the insertion of the ferrous form of iron into protoporphyrin IX in the heme synthesis pathway. Mutations in this gene are associated with erythropoietic protoporphyria. Two transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome 3.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

423 residues, UniProt reviewed canonical sequence.

>P22830|FECH
     1  MRSLGANMAA ALRAAGVLLR DPLASSSWRV CQPWRWKSGA AAAAVTTETA QHAQGAKPQV
    61  QPQKRKPKTG ILMLNMGGPE TLGDVHDFLL RLFLDRDLMT LPIQNKLAPF IAKRRTPKIQ
   121  EQYRRIGGGS PIKIWTSKQG EGMVKLLDEL SPNTAPHKYY IGFRYVHPLT EEAIEEMERD
   181  GLERAIAFTQ YPQYSCSTTG SSLNAIYRYY NQVGRKPTMK WSTIDRWPTH HLLIQCFADH
   241  ILKELDHFPL EKRSEVVILF SAHSLPMSVV NRGDPYPQEV SATVQKVMER LEYCNPYRLV
   301  WQSKVGPMPW LGPQTDESIK GLCERGRKNI LLVPIAFTSD HIETLYELDI EYSQVLAKEC
   361  GVENIRRAES LNGNPLFSKA LADLVHSHIQ SNELCSKQLT LSCPLCVNPV CRETKSFFTS
   421  QQL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FECH 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

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FECH.

Disease | AllUniProt

Conditions FECH is implicated in, by any mechanism.

• Protoporphyria, erythropoietic, 1 (EPP1) MIM:177000

Disease | GeneticClinVar

78 pathogenic / likely-pathogenic of 306 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Protoporphyria, erythropoietic, 1
• FECH-related disorder
• Autosomal erythropoietic protoporphyria
• See cases

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)

0.62

gnomAD pLI

0

gnomAD missense Z

1.34

DepMap mean gene effect

-0.49

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to dexamethasone stimulus
• cholesterol metabolic process
• erythrocyte differentiation
• generation of precursor metabolites and energy
• heme A biosynthetic process
• heme B biosynthetic process
• heme biosynthetic process
• multicellular organismal-level iron ion homeostasis
• protoporphyrinogen IX metabolic process
• response to arsenic-containing substance
• response to ethanol
• response to insecticide
• response to lead ion
• response to light stimulus
• response to methylmercury
• response to platinum ion
• response to xenobiotic stimulus
• very-low-density lipoprotein particle assembly
• detection of UV
• regulation of hemoglobin biosynthetic process

Molecular functions

• 2 iron, 2 sulfur cluster binding
• ferrous iron binding
• heme binding
• identical protein binding
• iron-responsive element binding
• protein homodimerization activity
• ferrochelatase activity

Cellular components

• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Ferrochelatase
• Ferrochelatase, active site
• Ferrochelatase, C-terminal
• Ferrochelatase, N-terminal
• Ferrochelatase

KeywordsUniProt

• 2Fe-2S
• Acetylation
• Heme biosynthesis
• Iron
• Iron-sulfur
• Lyase
• Membrane
• Metal-binding
• Mitochondrion
• Mitochondrion inner membrane
• Porphyrin biosynthesis
• Transit peptide

InteractionsUniProt · HPA

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

• ABCB10
• ABCB7
• PGRMC1
• SLC25A37
• FXN
• CALM1