Human Gene FECH (ENST00000262093.10) Description and Page Index
  Description: Homo sapiens ferrochelatase (FECH), transcript variant 2, mRNA. (from RefSeq NM_000140)
RefSeq Summary (NM_000140): 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]. Sequence Note: The RefSeq transcript and protein were derived from genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: BX571744.1, BC039841.1 [ECO:0000332] ##Evidence-Data-END## ##RefSeq-Attributes-START## gene product(s) localized to mito. :: reported by MitoCarta RefSeq Select criteria :: based on manual assertion, conservation, expression ##RefSeq-Attributes-END##
Gencode Transcript: ENST00000262093.10
Gencode Gene: ENSG00000066926.11
Transcript (Including UTRs)
   Position: hg38 chr18:57,544,389-57,586,702 Size: 42,314 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr18:57,550,712-57,586,620 Size: 35,909 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr18:57,544,389-57,586,702)mRNA (may differ from genome)Protein (423 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
LynxMGIneXtProtOMIMPubMedReactome
Stanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
  ID: HEMH_HUMAN
DESCRIPTION: RecName: Full=Ferrochelatase, mitochondrial; EC=4.99.1.1; AltName: Full=Heme synthase; AltName: Full=Protoheme ferro-lyase; Flags: Precursor;
FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX.
CATALYTIC ACTIVITY: Protoheme + 2 H(+) = protoporphyrin + Fe(2+).
COFACTOR: Binds 1 2Fe-2S cluster.
ENZYME REGULATION: Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor.
PATHWAY: Porphyrin metabolism; protoheme biosynthesis; protoheme from protoporphyrin-IX: step 1/1.
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
DISEASE: Defects in FECH are the cause of erythropoietic protoporphyria (EPP) [MIM:177000]. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. EPP is a form of porphyria marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.
SIMILARITY: Belongs to the ferrochelatase family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FECH";
WEB RESOURCE: Name=Wikipedia; Note=Ferrochelatase entry; URL="http://en.wikipedia.org/wiki/Ferrochelatase";

-  MalaCards Disease Associations
  MalaCards Gene Search: FECH
Diseases sorted by gene-association score: protoporphyria, erythropoietic, autosomal recessive* (1682), inherited metabolic disorder (25), porphyria (20), acute porphyria (19), x-linked protoporphyria (13), coproporphyria (12), porphyria cutanea tarda (10), porphyria, congenital erythropoietic (10), porphyria variegata (9), porphyria, acute intermittent (9), cutaneous porphyria (8), anemia, sideroblastic, 1 (6), liver disease (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.88 RPKM in Adrenal Gland
Total median expression: 291.68 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -43.6082-0.532 Picture PostScript Text
3' UTR -2017.606323-0.319 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001015 - Ferrochelatase
IPR019772 - Ferrochelatase_AS

Pfam Domains:
PF00762 - Ferrochelatase

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1HRK
- X-ray MuPIT

2HRC
- X-ray MuPIT

2HRE
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2PNJ - X-ray MuPIT 2PO5 - X-ray MuPIT 2PO7 - X-ray MuPIT
2QD1 - X-ray MuPIT 2QD2 - X-ray MuPIT 2QD3 - X-ray MuPIT
2QD4 - X-ray MuPIT 2QD5 - X-ray MuPIT 3AQI - X-ray MuPIT
3HCN - X-ray MuPIT 3HCO - X-ray MuPIT 3HCP - X-ray MuPIT
3HCR - X-ray MuPIT 4F4D - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P22830
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologGenome BrowserNo orthologGenome Browser
Gene Details    Gene Details
Gene Sorter    Gene Sorter
 RGDEnsemblEnsembl SGD
 Protein Sequence Protein Sequence Protein Sequence
 Alignment Alignment Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004325 ferrochelatase activity
GO:0005515 protein binding
GO:0008198 ferrous iron binding
GO:0016829 lyase activity
GO:0046872 metal ion binding
GO:0051536 iron-sulfur cluster binding
GO:0051537 2 iron, 2 sulfur cluster binding

Biological Process:
GO:0006091 generation of precursor metabolites and energy
GO:0006779 porphyrin-containing compound biosynthetic process
GO:0006783 heme biosynthetic process
GO:0009416 response to light stimulus
GO:0010038 response to metal ion
GO:0010288 response to lead ion
GO:0017085 response to insecticide
GO:0042493 response to drug
GO:0045471 response to ethanol
GO:0046501 protoporphyrinogen IX metabolic process
GO:0046685 response to arsenic-containing substance
GO:0051597 response to methylmercury
GO:0070541 response to platinum ion
GO:0071549 cellular response to dexamethasone stimulus

Cellular Component:
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005759 mitochondrial matrix
GO:0016020 membrane


-  Descriptions from all associated GenBank mRNAs
  LP747422 - Sequence 9 from Patent WO2018009939.
JD489315 - Sequence 470339 from Patent EP1572962.
JD337579 - Sequence 318603 from Patent EP1572962.
JD213065 - Sequence 194089 from Patent EP1572962.
JD220933 - Sequence 201957 from Patent EP1572962.
JD371277 - Sequence 352301 from Patent EP1572962.
JD542915 - Sequence 523939 from Patent EP1572962.
JD514440 - Sequence 495464 from Patent EP1572962.
JD560952 - Sequence 541976 from Patent EP1572962.
JD165228 - Sequence 146252 from Patent EP1572962.
JD117101 - Sequence 98125 from Patent EP1572962.
JD043146 - Sequence 24170 from Patent EP1572962.
JD043144 - Sequence 24168 from Patent EP1572962.
JD043145 - Sequence 24169 from Patent EP1572962.
JD491925 - Sequence 472949 from Patent EP1572962.
BX571744 - Homo sapiens mRNA; cDNA DKFZp686P18130 (from clone DKFZp686P18130).
AK223190 - Homo sapiens mRNA for Hypothetical protein DKFZp686P18130 variant, clone: REC00205.
BC039841 - Homo sapiens ferrochelatase (protoporphyria), mRNA (cDNA clone MGC:48846 IMAGE:6042757), complete cds.
AK092416 - Homo sapiens cDNA FLJ35097 fis, clone PLACE6006222, highly similar to FERROCHELATASE PRECURSOR (EC 4.99.1.1).
D00726 - Homo sapiens mRNA for ferrochelatase, complete cds.
FB729825 - Sequence 1 from Patent EP1897941.
JD553122 - Sequence 534146 from Patent EP1572962.
JD193264 - Sequence 174288 from Patent EP1572962.
JD408070 - Sequence 389094 from Patent EP1572962.
JD158047 - Sequence 139071 from Patent EP1572962.
JD243528 - Sequence 224552 from Patent EP1572962.
JD045078 - Sequence 26102 from Patent EP1572962.
JD149679 - Sequence 130703 from Patent EP1572962.
JD077394 - Sequence 58418 from Patent EP1572962.
JD342839 - Sequence 323863 from Patent EP1572962.
JD038829 - Sequence 19853 from Patent EP1572962.
JD171422 - Sequence 152446 from Patent EP1572962.
AK292937 - Homo sapiens cDNA FLJ76483 complete cds, highly similar to Homo sapiens ferrochelatase (protoporphyria) (FECH), mRNA.
JD519220 - Sequence 500244 from Patent EP1572962.
AK299643 - Homo sapiens cDNA FLJ56930 complete cds, highly similar to Ferrochelatase, mitochondrial precursor (EC 4.99.1.1).
JD499146 - Sequence 480170 from Patent EP1572962.
JD509741 - Sequence 490765 from Patent EP1572962.
BT019958 - Homo sapiens ferrochelatase (protoporphyria) mRNA, complete cds.
BT019959 - Homo sapiens ferrochelatase (protoporphyria) mRNA, complete cds.
KJ891157 - Synthetic construct Homo sapiens clone ccsbBroadEn_00551 FECH gene, encodes complete protein.
KR712041 - Synthetic construct Homo sapiens clone CCSBHm_00035018 FECH (FECH) mRNA, encodes complete protein.
KR712042 - Synthetic construct Homo sapiens clone CCSBHm_00035031 FECH (FECH) mRNA, encodes complete protein.
KR712043 - Synthetic construct Homo sapiens clone CCSBHm_00035043 FECH (FECH) mRNA, encodes complete protein.
KR712044 - Synthetic construct Homo sapiens clone CCSBHm_00035054 FECH (FECH) mRNA, encodes complete protein.
AB529061 - Synthetic construct DNA, clone: pF1KB3821, Homo sapiens FECH gene for ferrochelatase, without stop codon, in Flexi system.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00860 - Porphyrin and chlorophyll metabolism
hsa01100 - Metabolic pathways

BioCyc Knowledge Library
HEME-BIOSYNTHESIS-II - heme biosynthesis from uroporphyrinogen-III I
PWY-5920 - heme biosynthesis

BioCarta from NCI Cancer Genome Anatomy Project
h_ahspPathway - Hemoglobin's Chaperone

Reactome (by CSHL, EBI, and GO)

Protein P22830 (Reactome details) participates in the following event(s):

R-HSA-189465 FECH binds Fe2+ to PRIN9 to form heme
R-HSA-189451 Heme biosynthesis
R-HSA-189445 Metabolism of porphyrins
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A8KA72, HEMH_HUMAN, NM_000140, P22830, Q8IXN1, Q8NAN0, uc002lgq.1, uc002lgq.2, uc002lgq.3, uc002lgq.4, uc002lgq.5, uc002lgq.6
UCSC ID: uc002lgq.6
RefSeq Accession: NM_000140
Protein: P22830 (aka HEMH_HUMAN or HEMZ_HUMAN)
CCDS: CCDS11964.1, CCDS32836.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene FECH:
epp-ar (Erythropoietic Protoporphyria, Autosomal Recessive)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.