RBCK1

Chr 20AR

RANBP2-type and C3HC4-type zinc finger containing 1

Also known as: C20orf18, HOIL-1, HOIL1, PBMEI, PGBM1, RBCK2, RNF54, UBCE7IP3

NCBI Gene: 10616 ENSG00000125826 UniProt: Q9BYM8 OMIM: 610924

RBCK1 encodes an E3 ubiquitin ligase that is a component of the LUBAC complex, which conjugates linear polyubiquitin chains to substrates and plays a key role in NF-kappa-B signaling, inflammation regulation, and innate immunity. Biallelic mutations cause polyglucosan body myopathy 1 with or without immunodeficiency, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.453), reflecting its essential cellular functions.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables several functions, including identical protein binding activity; transcription coactivator activity; and ubiquitin binding activity. Involved in several processes, including positive regulation of canonical NF-kappaB signal transduction; protein linear polyubiquitination; and regulation of DNA-binding transcription factor activity. Part of LUBAC complex. Implicated in glycogen storage disease. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.451 OMIM phenotype

Clinical Summary— RBCK1

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Gene-Disease Validity (ClinGen)

polyglucosan body myopathy 1 with or without immunodeficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.135

Z-score 3.92

OE 0.25 (0.15–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.00Z-score

OE missense 0.69 (0.62–0.77)

227 obs / 329.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.25 (0.15–0.45)

0≤0.351.4

Missense OE?0.69 (0.62–0.77)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 8 / 31.9Missense obs/exp: 227 / 329.3Syn Z: 0.25

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongRBCK1-related polyglucosan body cardiac and skeletal myopathy with or without immunodeficiencyLOFAR

This gene — mechanism propensity

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

0.5476th %ile

GOF

0.6637th %ile

LOF

0.3066th %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.