FECH

ferrochelatase

Basic information

Region (hg38): 18:57544377-57586732

Links

ENSG00000066926 ∙ NCBI:2235 ∙ OMIM:612386 ∙ HGNC:3647 ∙ Uniprot:P22830 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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; 37043653
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 ClinVar and linked to the FECH gene.

• not provided (32 variants)
• Protoporphyria, erythropoietic, 1 (10 variants)
• FECH-related disorder (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				18	5	23
missense	2	6	50	5	2	65
nonsense	8	1	1			10
start loss			1			1
frameshift	12	2				14
inframe indel						0
splice donor/acceptor (+/-2bp)	8	5		1		14
splice region	2		8	13		23
non coding			49	55	50	154
Total	30	14	101	79	57

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: gnomAD

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: dbNSFP

• 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