ERFE

Chr 2

erythroferrone

Also known as: C1QTNF15, CTRP15, FAM132B

The protein erythroferrone is an iron-regulatory hormone produced by erythroblasts that suppresses hepatic hepcidin expression to promote iron absorption and mobilization from stores following blood loss. Pathogenic variants in ERFE cause autosomal recessive iron refractory iron deficiency anemia (IRIDA), a disorder characterized by severe iron deficiency anemia that does not respond to oral iron supplementation and responds poorly to parenteral iron. The gene shows tolerance to loss-of-function variants (LOEUF 1.28), which is consistent with the recessive inheritance pattern of the associated iron metabolism disorder.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.28
Clinical SummaryERFE
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.003
Z-score 1.04
OE 0.61 (0.321.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.67Z-score
OE missense 0.82 (0.690.98)
86 obs / 105.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.321.28)
00.351.4
Missense OE0.82 (0.690.98)
00.61.4
Synonymous OE0.74
01.21.6
LoF obs/exp: 5 / 8.2Missense obs/exp: 86 / 105.2Syn Z: 1.40
DN
0.6162th %ile
GOF
0.5171th %ile
LOF
0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ERFE · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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