FECH ferrochelatase [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Associated conditions

Description	Tests
Protoporphyria, erythropoietic, 1 MedGen: C4692546 OMIM: 177000 GeneReviews: Erythropoietic Protoporphyria, Autosomal Recessive	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

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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

FECH__4993 (e-PCR)
- UniSTS:462890

RH36328 (e-PCR)
- UniSTS:48971

RH102529 (e-PCR)
- UniSTS:96863

RH17513 (e-PCR)
- UniSTS:53114

SHGC-81615 (e-PCR)
- UniSTS:103557

SHGC-79296 (e-PCR)
- UniSTS:102808

WI-20204 (e-PCR)
- UniSTS:1950

RH44862 (e-PCR)
- UniSTS:57797

STS-D00726 (e-PCR)
- UniSTS:46300

D7S2739 (e-PCR)
- UniSTS:22753

GDB:196608 (e-PCR)
- UniSTS:155875

D15S1390 (e-PCR)
- UniSTS:474340

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

EC 4.98.1.1

NP_001012533.1

EC 4.98.1.1

NP_001358023.1

EC 4.98.1.1

NP_001358024.1

EC 4.98.1.1

NP_001361707.1

EC 4.98.1.1

XP_011524183.1

EC 4.98.1.1

XP_054174264.1

EC 4.98.1.1

NCBI Reference Sequences (RefSeq)

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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

NG_008175.1 RefSeqGene

Range

5036..47361

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_1080

mRNA and Protein(s)

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
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
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
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
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

NC_000018.10 Reference GRCh38.p14 Primary Assembly

Range

57544377..57586702 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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