FECH
ferrochelatase
Basic information
Region (hg38): 18:57544376-57586732
Links
Phenotypes
GenCC
Source:
- protoporphyria, erythropoietic, 1 (Strong), mode of inheritance: AR
- autosomal erythropoietic protoporphyria (Supportive), mode of inheritance: AD
- protoporphyria, erythropoietic, 1 (Definitive), mode of inheritance: AR
- protoporphyria, erythropoietic, 1 (Strong), mode of inheritance: AR
- protoporphyria, erythropoietic, 1 (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Protoporphyria, erythropoietic 1 | AD/AR | Dermatologic; Gastrointestinal | While the only manifestation in many individuals is photosensitivity (for which light avoidance and possible medical treatment, such as with alpha-melanocyte-stimulating hormone analog, can be beneficial), some individuals can have severe liver sequelae, and surveillance and medical treatment (eg, with cholestyramine) can be beneficial; BMT and liver transplantation may be necessary | Dermatologic; Gastrointestinal; Hematologic | 14072370; 5835322; 14338805; 6019665; 5536249; 1138541; 1251847; 911406; 3805002; 6742776; 2384686; 1755842; 8571955; 8601739; 9649563; 9585598; 11039124; 11753383; 12601550; 16385445; 17875872; 19144952; 18787536; 19744342; 20857522; 21659066; 22971305; 23016163; 23323258; 23600449 |
| The inheritance pattern can be complex, and can involve a deleterious variant in trans with a "low-normal" polymorphism (sometimes termed "pseudodominant" inheritance), as well as homozygosity/compound heterozygosity for deleterious variants; Agents associated with hepatic dysfunction should be avoided |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (152 variants)
- Protoporphyria, erythropoietic, 1 (150 variants)
- Inborn genetic diseases (12 variants)
- not specified (6 variants)
- Autosomal erythropoietic protoporphyria (2 variants)
- Jaundice;Erythema (2 variants)
- FECH-related condition (2 variants)
- - (2 variants)
- Increased erythrocyte protoporphyrin concentration (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FECH gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 13 | 19 | ||||
| missense | 40 | 52 | ||||
| nonsense | 9 | |||||
| start loss | 1 | |||||
| frameshift | 12 | 14 | ||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| splice region ? | 2 | 7 | 8 | 1 | 18 | |
| non coding ? | 49 | 49 | 50 | 148 | ||
| Total | 29 | 12 | 91 | 66 | 58 |
Highest pathogenic variant AF is 0.0000657
Variants in FECH
This is a list of pathogenic ClinVar variants found in the FECH region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 18-57544911-A-C | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545084-G-T | Protoporphyria, erythropoietic, 1 | Benign (Jun 14, 2016) | ||
| 18-57545124-C-T | Protoporphyria, erythropoietic, 1 | Benign (Jun 14, 2016) | ||
| 18-57545318-C-A | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545363-G-A | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) | ||
| 18-57545465-A-G | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) | ||
| 18-57545542-A-G | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) | ||
| 18-57545569-G-A | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545572-C-T | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545573-G-A | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545622-C-T | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) | ||
| 18-57545741-T-C | Protoporphyria, erythropoietic, 1 | Benign (Jun 14, 2016) | ||
| 18-57545820-C-CA | Protoporphyria, erythropoietic, 1 | Benign (Jun 14, 2016) | ||
| 18-57545826-A-C | Protoporphyria, erythropoietic, 1 | Benign (Jun 14, 2016) | ||
| 18-57545828-A-AG | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545883-G-A | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545913-TTAA-T | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57545992-A-G | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) | ||
| 18-57546114-A-C | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) | ||
| 18-57546115-A-G | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57546149-C-A | Protoporphyria, erythropoietic, 1 | Benign (Jun 14, 2016) | ||
| 18-57546184-G-A | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) | ||
| 18-57546249-T-C | Protoporphyria, erythropoietic, 1 | Benign (Jun 14, 2016) | ||
| 18-57546254-G-A | Protoporphyria, erythropoietic, 1 | Likely benign (Jun 14, 2016) | ||
| 18-57546263-T-C | Protoporphyria, erythropoietic, 1 | Uncertain significance (Jun 14, 2016) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FECH | protein_coding | protein_coding | ENST00000382873 | 11 | 38490 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00276 | 0.997 | 125726 | 0 | 22 | 125748 | 0.0000875 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.34 | 175 | 232 | 0.753 | 0.0000127 | 2790 |
| Missense in Polyphen | 66 | 91.479 | 0.72147 | 1097 | ||
| Synonymous | 0.647 | 83 | 90.8 | 0.914 | 0.00000574 | 827 |
| Loss of Function | 3.03 | 9 | 25.5 | 0.353 | 0.00000136 | 287 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000213 | 0.000213 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.000141 | 0.000141 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the ferrous insertion into protoporphyrin IX.;
- Disease
- DISEASE: Protoporphyria, erythropoietic, 1 (EPP1) [MIM:177000]: An autosomal recessive form of porphyria with onset usually before age 10 years. 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. Erythropoietic protoporphyria is 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. {ECO:0000269|PubMed:10942404, ECO:0000269|PubMed:11375302, ECO:0000269|PubMed:12063482, ECO:0000269|PubMed:12601550, ECO:0000269|PubMed:1376018, ECO:0000269|PubMed:15286165, ECO:0000269|PubMed:17196862, ECO:0000269|PubMed:1755842, ECO:0000269|PubMed:7910885, ECO:0000269|PubMed:8757534, ECO:0000269|PubMed:9211198, ECO:0000269|PubMed:9585598, ECO:0000269|PubMed:9740232}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Porphyrin and chlorophyll metabolism - Homo sapiens (human);Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Porphyrin Metabolism;Heme Biosynthesis;hemoglobins chaperone;Heme biosynthesis;Metabolism of porphyrins;Metabolism;Porphyrin metabolism;Porphyrin metabolism;HIF-1-alpha transcription factor network;heme biosynthesis from uroporphyrinogen-III I;heme biosynthesis
(Consensus)
Recessive Scores
- pRec
- 0.303
Intolerance Scores
- loftool
- 0.0817
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 57.31
Haploinsufficiency Scores
- pHI
- 0.438
- hipred
- Y
- hipred_score
- 0.589
- ghis
- 0.396
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.986
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fech
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- fech
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- increased fluorescence
Gene ontology
- Biological process
- generation of precursor metabolites and energy;heme biosynthetic process;response to light stimulus;response to lead ion;response to insecticide;response to ethanol;protoporphyrinogen IX metabolic process;response to arsenic-containing substance;response to methylmercury;response to platinum ion;cellular response to dexamethasone stimulus
- Cellular component
- mitochondrion;mitochondrial inner membrane;mitochondrial matrix
- Molecular function
- ferrochelatase activity;protein binding;ferrous iron binding;2 iron, 2 sulfur cluster binding