CYB5D1

Chr 17

cytochrome b5 domain containing 1

NCBI Gene: 124637 ENSG00000182224 UniProt: Q6P9G0

The protein is a radial spoke stalk component that binds heme and is required for coordinated ciliary beating, likely through redox signaling pathways. Mutations cause primary ciliary dyskinesia with typical respiratory symptoms and potential laterality defects. This gene follows autosomal recessive inheritance and is highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

Predicted to enable metal ion binding activity. Predicted to be involved in cilium movement and regulation of cilium beat frequency. Predicted to be located in cell projection; cytoplasm; and cytoskeleton. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.83

Clinical Summary— CYB5D1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

45 VUS of 51 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.83LOEUF

pLI 0.000

Z-score -0.71

OE 1.24 (0.80–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.86Z-score

OE missense 0.79 (0.68–0.93)

107 obs / 135.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.24 (0.80–1.83)

0≤0.351.4

Missense OE?0.79 (0.68–0.93)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 13 / 10.5Missense obs/exp: 107 / 135.2Syn Z: 0.10

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

VUS45

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	45	45
Likely Benign	2	2
Benign	0	0
Total	47	47

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

22 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap CYB5D1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →