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FECH ferrochelatase [ Homo sapiens (human) ]

Gene ID: 2235, updated on 3-Apr-2024

Summary

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Official Symbol
FECHprovided by HGNC
Official Full Name
ferrochelataseprovided by HGNC
Primary source
HGNC:HGNC:3647
See related
Ensembl:ENSG00000066926 MIM:612386; AllianceGenome:HGNC:3647
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EPP; FCE; EPP1
Summary
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]
Expression
Broad expression in bone marrow (RPKM 19.5), kidney (RPKM 8.4) and 24 other tissues See more
Orthologs
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Genomic context

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See FECH in Genome Data Viewer
Location:
18q21.31
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (57544377..57586702, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (57744729..57787055, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (55211609..55253934, complement)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9477 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:55101332-55101912 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:55101913-55102492 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9478 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:55104607-55105362 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:55106119-55106874 Neighboring gene FOXA motif-containing MPRA enhancer 78 Neighboring gene one cut homeobox 2 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_48194 and experimental_48198 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48219 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_48245 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13369 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13370 Neighboring gene MPRA-validated peak3163 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr18:55230082-55230255 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13371 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13372 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13373 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9479 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9480 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9481 Neighboring gene Sharpr-MPRA regulatory region 4588 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:55288917-55289621 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13375 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:55297311-55297811 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:55300102-55300950 Neighboring gene ATP8B1 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:55310728-55311239 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:55311240-55311750 Neighboring gene asparaginyl-tRNA synthetase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13377 Neighboring gene ATPase phospholipid transporting 8B1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Novel mutation of the ferrochelatase gene in a Japanese family with erythropoietic protoporphyria. Saito A, et al. J Dermatol, 2020 Apr. PMID 32056258
  2. Targeted resequencing of FECH locus reveals that a novel deep intronic pathogenic variant and eQTLs may cause erythropoietic protoporphyria (EPP) through a methylation-dependent mechanism. Chiara M, et al. Genet Med, 2020 Jan. PMID 31273344
  3. Ferrochelatase Deficiency Abrogated the Enhancement of Aminolevulinic Acid-mediated Protoporphyrin IX by Iron Chelator Deferoxamine. Palasuberniam P, et al. Photochem Photobiol, 2019 Jul. PMID 30767226, Free PMC Article
  4. Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans. Wang H, et al. Hum Mol Genet, 2019 Feb 15. PMID 30403821, Free PMC Article
  5. Digital PCR (dPCR) analysis reveals that the homozygous c.315-48T>C variant in the FECH gene might cause erythropoietic protoporphyria (EPP). Brancaleoni V, et al. Mol Genet Metab, 2018 Aug. PMID 29941360

See all (159) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness.
    Title: Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness.
  2. Cockayne syndrome group A and ferrochelatase finely tune ribosomal gene transcription and its response to UV irradiation.
    Title: Cockayne syndrome group A and ferrochelatase finely tune ribosomal gene transcription and its response to UV irradiation.
  3. Novel mutation of the ferrochelatase gene in a Japanese family with erythropoietic protoporphyria.
    Title: Novel mutation of the ferrochelatase gene in a Japanese family with erythropoietic protoporphyria.
  4. This study demonstrates that FECH activity is an important determinant of tumor response to deferoxamine treatment.
    Title: Ferrochelatase Deficiency Abrogated the Enhancement of Aminolevulinic Acid-mediated Protoporphyrin IX by Iron Chelator Deferoxamine.
  5. These results expand the molecular heterogeneity of the erythropoietic porphyrias by adding a total of 20 novel mutations in ferrochelatase.
    Title: Congenital erythropoietic porphyria and erythropoietic protoporphyria: Identification of 7 uroporphyrinogen III synthase and 20 ferrochelatase novel mutations.
  6. Our data show that there is a metabolic link between the activity ferrochelatase and levels of MFRN1 mRNA. We examined the correlation between ferrochelatase activity and MFRN1 mRNA in cell lines established from patients with the classical protoporphyria.
    Title: Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria.
  7. Study reports evidence of a deep intronic variant causing erythropoietic protoporphyria. The c.464-1169 A>C intronic substitution (p.Ala155ValfsTer22) disrupts, likely through the institution of new methylated CpG site, an exonic splicing silencer site causing the insertion of a "cryptic exon" containing a stop codon, in the mature FECH transcript.
    Title: Targeted resequencing of FECH locus reveals that a novel deep intronic pathogenic variant and eQTLs may cause erythropoietic protoporphyria (EPP) through a methylation-dependent mechanism.
  8. Follow-up joint ancestry-SNP association analyses identified novel variants in ferrochelatase (FECH), significantly associated with AHI and percentage time SaO2 < 90% after adjusting for multiple tests (P < 8 x 10-6)
    Title: Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans.
  9. FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity
    Title: FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity.
  10. The results of FECH gene expression suggested that the homozygosity for the c.315-48T>C variant could be considered pathological. Thus, this study identified the homozygotes for the c.315-48T>C variant as pathological. By extension, when the samples were categorised according to the haplotypes, the GTC haplotype in homozygosis was pathological.
    Title: Digital PCR (dPCR) analysis reveals that the homozygous c.315-48T>C variant in the FECH gene might cause erythropoietic protoporphyria (EPP).
Submit: New GeneRIF Correction See all GeneRIFs (61)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Pol gag-pol HIV-1 Pol is identified to have a physical interaction with ferrochelatase (FECH) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 2 iron, 2 sulfur cluster binding IEA
Inferred from Electronic Annotation
more info
  
enables ferrochelatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ferrochelatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ferrous iron binding TAS
Traceable Author Statement
more info
 PubMed 
enables heme binding IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables iron-responsive element binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in cellular response to dexamethasone stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in cholesterol metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in detection of UV IEA
Inferred from Electronic Annotation
more info
  
involved_in erythrocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in generation of precursor metabolites and energy TAS
Traceable Author Statement
more info
 PubMed 
involved_in heme A biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in heme B biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in heme O biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in heme biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in heme biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in multicellular organismal-level iron ion homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in protoporphyrinogen IX metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of eIF2 alpha phosphorylation by heme IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of hemoglobin biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in response to arsenic-containing substance IEA
Inferred from Electronic Annotation
more info
  
involved_in response to ethanol IEA
Inferred from Electronic Annotation
more info
  
involved_in response to insecticide IEA
Inferred from Electronic Annotation
more info
  
involved_in response to lead ion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to light stimulus TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to methylmercury IEA
Inferred from Electronic Annotation
more info
  
involved_in response to platinum ion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in very-low-density lipoprotein particle assembly IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in mitochondrial inner membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
ferrochelatase, mitochondrial
Names
heme synthase
heme synthetase
protoheme ferro-lyase
protoporphyria
NP_000131.2
NP_001012533.1
NP_001358023.1
NP_001358024.1
NP_001361707.1
XP_011524183.1
XP_054174264.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008175.1 RefSeqGene

    Range
    5036..47361
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1080

mRNA and Protein(s)

  1. NM_000140.5 → NP_000131.2  ferrochelatase, mitochondrial isoform b precursor

    See identical proteins and their annotated locations for NP_000131.2

    Status: REVIEWED

    Source sequence(s)
    AC100847
    Consensus CDS
    CCDS11964.1
    UniProtKB/Swiss-Prot
    A8KA72, P22830, Q8IXN1, Q8NAN0
    UniProtKB/TrEMBL
    Q5TZY0
    Related
    ENSP00000262093.6, ENST00000262093.11
    Conserved Domains (1) summary
    pfam00762
    Location:69 → 389
    Ferrochelatase; Ferrochelatase

  2. NM_001012515.4 → NP_001012533.1  ferrochelatase, mitochondrial isoform a precursor

    See identical proteins and their annotated locations for NP_001012533.1

    Status: REVIEWED

    Source sequence(s)
    AC100847
    Consensus CDS
    CCDS32836.1
    UniProtKB/TrEMBL
    Q5TZY0
    Related
    ENSP00000498358.1, ENST00000652755.1
    Conserved Domains (3) summary
    cd00419
    Location:241 → 378
    Ferrochelatase_C; Ferrochelatase, C-terminal domain: Ferrochelatase (protoheme ferrolyase or HemH) is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ...
    cd03411
    Location:75 → 236
    Ferrochelatase_N; Ferrochelatase, N-terminal domain: Ferrochelatase (protoheme ferrolyase or HemH) is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ...
    pfam00762
    Location:75 → 395
    Ferrochelatase; Ferrochelatase

  3. NM_001371094.1 → NP_001358023.1  ferrochelatase, mitochondrial isoform c

    Status: REVIEWED

    Source sequence(s)
    AC100847, BC039841
    UniProtKB/TrEMBL
    Q5TZY0
    Related
    ENSP00000466263.1, ENST00000592699.6
    Conserved Domains (1) summary
    pfam00762
    Location:68 → 356
    Ferrochelatase

  4. NM_001371095.1 → NP_001358024.1  ferrochelatase, mitochondrial isoform d

    Status: REVIEWED

    Source sequence(s)
    AC100847, BC039841, DC341584
    Consensus CDS
    CCDS92465.1
    UniProtKB/TrEMBL
    A0A499FJN5, Q7KZA3
    Related
    ENSP00000372326.4, ENST00000382873.8
    Conserved Domains (1) summary
    pfam00762
    Location:1 → 317
    Ferrochelatase

  5. NM_001374778.1 → NP_001361707.1  ferrochelatase, mitochondrial isoform e

    Status: REVIEWED

    Source sequence(s)
    AC100847
    UniProtKB/TrEMBL
    Q5TZY0
    Conserved Domains (1) summary
    pfam00762
    Location:68 → 369
    Ferrochelatase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    57544377..57586702 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011525881.2 → XP_011524183.1  ferrochelatase, mitochondrial isoform X1

    UniProtKB/TrEMBL
    Q5TZY0
    Conserved Domains (3) summary
    cd00419
    Location:235 → 345
    Ferrochelatase_C; Ferrochelatase, C-terminal domain: Ferrochelatase (protoheme ferrolyase or HemH) is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ...
    cd03411
    Location:75 → 236
    Ferrochelatase_N; Ferrochelatase, N-terminal domain: Ferrochelatase (protoheme ferrolyase or HemH) is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ...
    pfam00762
    Location:75 → 362
    Ferrochelatase; Ferrochelatase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    57744729..57787055 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054318289.1 → XP_054174264.1  ferrochelatase, mitochondrial isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P22830.2 GenPept UniProtKB/Swiss-Prot:P22830

Gene LinkOut

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