FECH

Chr 18AR

ferrochelatase

Also known as: EPP, EPP1, FCE

The mitochondrial enzyme ferrochelatase catalyzes the insertion of ferrous iron into protoporphyrin IX in the final step of heme biosynthesis. Mutations cause erythropoietic protoporphyria, a metabolic disorder characterized by painful photosensitivity and potential liver complications, inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variants (pLI 0.003, LOEUF 0.616), consistent with the recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Protoporphyria, erythropoietic, 1MIM #177000
AR
0
Active trials
31
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.62
LOEUF
Mechanism
Clinical SummaryFECH
🧬
Gene-Disease Validity (ClinGen)
protoporphyria, erythropoietic, 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — FECH
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.003
Z-score 3.03
OE 0.35 (0.210.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.34Z-score
OE missense 0.75 (0.670.85)
175 obs / 232.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.210.62)
00.351.4
Missense OE0.75 (0.670.85)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 9 / 25.5Missense obs/exp: 175 / 232.4Syn Z: 0.65

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FECH · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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