RBCK1

Chr 20

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

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.

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 T cell receptor signaling pathway; positive regulation of canonical NF-kappaB signal transduction; and protein linear polyubiquitination. Part of LUBAC complex. Implicated in glycogen storage disease. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPolyglucosan body myopathy 1 with or without immunodeficiency

Clinical highlights

Gene-disease validity (ClinGen)

polyglucosan body myopathy 1 with or without immunodeficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429