RBCK1 Gene - RANBP2-Type and C3HC4-Type Zinc Finger Containing 1
E3 ubiquitin-protein ligase involved in immune signaling and proteostasis
Gene Information Card
| Symbol | RBCK1 |
|---|---|
| Full Name | RANBP2-Type and C3HC4-Type Zinc Finger Containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 10616 ncbi.nlm.nih.gov/gene/10616 |
| Ensembl ID | ENSG00000125826 |
| UniProt ID | Q9BZT8 |
| OMIM ID | 610924 |
| HGNC ID | 15864 |
| Aliases | HOIL-1, HOIL1, RBCK1, UBCE7IP3, XAP3, ZNF147 |
Description
The RBCK1 gene encodes heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1), a component of the linear ubiquitin chain assembly complex (LUBAC). HOIL-1 functions as an E3 ubiquitin-protein ligase that generates linear (M1-linked) ubiquitin chains, playing a critical role in NF-κB activation, innate immune signaling, and protein homeostasis. Mutations in RBCK1 cause immunodeficiency with polyglucosan body myopathy and autoinflammation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 44 (IMD44) with polyglucosan body myopathy | Loss-of-function mutations impair LUBAC-mediated linear ubiquitination, leading to dysregulated NF-κB signaling and accumulation of polyglucosan bodies in muscle. | OMIM #615895; ClinVar |
| Polyglucosan body myopathy 1 (PGBM1) | Defective linear ubiquitination disrupts autophagy and glycogen metabolism, causing polyglucosan accumulation in skeletal and cardiac muscle. | OMIM #615895; NCBI GeneReviews |
| Autoinflammatory syndrome | Impaired NF-κB regulation due to RBCK1 deficiency leads to chronic inflammation and recurrent infections. | OMIM #615895; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 10.8 | Medium |
| Liver | 8.3 | Medium |
| Brain | 5.2 | Low |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression |
| HeLa | 9.7 | Medium |
| K562 | 6.4 | Low |
| HepG2 | 7.1 | Medium |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.899G>A (p.Arg300Gln) | Missense | Rare | Impaired LUBAC assembly and reduced linear ubiquitination |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein expression |
| c.1112_1113del (p.Glu371Glyfs*4) | Frameshift | Rare | Premature truncation, loss of E3 ligase activity |
| c.550C>T (p.Arg184*) | Nonsense | Rare | Nonsense-mediated decay, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported RBCK1 mutations are loss-of-function, leading to reduced or absent HOIL-1 protein and impaired linear ubiquitination.
Gain of Function (GOF)
No gain-of-function mutations have been described for RBCK1.
Dominant Negative (DN)
No dominant-negative mutations have been reported; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Linear ubiquitination pathway (LUBAC complex)
• NF-kappaB signaling pathway
• TNF signaling pathway
• IL-1 signaling pathway
• Autophagy pathway
Protein Summary
HOIL-1 (RBCK1) is a 510-amino acid protein containing an N-terminal ubiquitin-like (UBL) domain, a RING-type zinc finger, and a C-terminal RBR (RING-between-RING) domain. It forms the LUBAC complex with HOIP and SHARPIN, catalyzing the formation of linear ubiquitin chains on target proteins such as NEMO and RIPK1. This modification is essential for NF-κB activation and immune responses. HOIL-1 also participates in iron metabolism by ubiquitinating IRP2.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RBCK1 Knockout HEK293 Cell Line | EDJ-KQ2503 | Human | 10616 | Details Get a Quote |
| RBCK1 Knockout A-549 Cell Line | EDJ-KQ24479 | Human | 10616 | Details Get a Quote |
| RBCK1 Knockout HCT 116 Cell Line | EDJ-KQ24481 | Human | 10616 | Details Get a Quote |
| RBCK1 Knockout HeLa Cell Line | EDJ-KQ24482 | Human | 10616 | Details Get a Quote |
