CYB5R3

Chr 22AR

cytochrome b5 reductase 3

Also known as: B5R, DIA1

Cytochrome b5 reductase catalyzes the reduction of cytochrome b5 using NADH, with the membrane-bound form functioning in fatty acid metabolism and cholesterol biosynthesis, and the soluble erythrocyte form reducing methemoglobin. Mutations cause autosomal recessive methemoglobinemia, which can be limited to erythrocytes (type I) or involve multiple organ systems with neurological manifestations (type II). The gene shows low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.852 OMIM phenotypes
Clinical SummaryCYB5R3
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Gene-Disease Validity (ClinGen)
methemoglobinemia due to deficiency of methemoglobin reductase · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.85LOEUF
pLI 0.000
Z-score 2.03
OE 0.49 (0.290.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.42Z-score
OE missense 1.08 (0.971.21)
222 obs / 205.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.49 (0.290.85)
00.351.4
Missense OE1.08 (0.971.21)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 9 / 18.4Missense obs/exp: 222 / 205.1Syn Z: 0.12
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCYB5R3-related methemoglobinemia due to deficiency of methemoglobin reductaseLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7228th %ile
GOF
0.75top 25%
LOF
0.2189th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CYB5R3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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