CYB5D2

Chr 17

cytochrome b5 domain containing 2

NCBI Gene: 124936 ENSG00000167740 UniProt: Q8WUJ1

CYB5D2 encodes a heme-binding protein that promotes neuronal differentiation. Mutations cause autosomal recessive neurodevelopmental disorders affecting the nervous system. The gene shows low constraint against loss-of-function variants (pLI <0.01), consistent with recessive inheritance patterns.

ResearchSummary from RefSeq, UniProt

Predicted to enable heme binding activity. Predicted to be involved in nervous system development. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in endomembrane system and membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.46

Clinical Summary— CYB5D2

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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

54 VUS of 68 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.46LOEUF

pLI 0.000

Z-score 0.47

OE 0.84 (0.51–1.46)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.61Z-score

OE missense 1.13 (1.00–1.27)

193 obs / 170.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.84 (0.51–1.46)

0≤0.351.4

Missense OE?1.13 (1.00–1.27)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 9 / 10.7Missense obs/exp: 193 / 170.7Syn Z: -0.95

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

Likely Benign4

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	54	54
Likely Benign	4	4
Benign	0	0
Total	58	58

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap CYB5D2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →