RNF220

Chr 1p34.1

ring finger protein 220

Aliases:: FLJ10597
MANE:: ENST00000361799.7

OMIM: 616136 ↗NCBI: 55182 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

RNF220 · Q5VTB9

v62025-08-01

Predicted Aligned Error matrix for RNF220 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

58.5/ 100

Low

566 residues

Confidence breakdown

Very high(≥ 90)17%
Confident(70–90)12%
Low(50–70)18%
Very low(< 50)53%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Ataxia and cerebellar anomalies - narrow panel
BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss
BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy
0.58
leukodystrophy
0.38
Ataxia
0.37
cerebellar ataxia
0.37
Abnormal corpus callosum morphology
0.37
Sensorineural hearing impairment
0.37
bone remodeling disease
0.28
Genu valgum
0.28
Genu varum
0.28
epistaxis
0.25

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

E3 ubiquitin-protein ligase RNF220

E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of multiple substrates including GRIA1, GRIA2, PHOX2A and PHOX2B, STAT1, STAT3 and SIN3B. Independently of its E3 ligase activity, acts as a CTNNB1 stabilizer through USP7-mediated deubiquitination of CTNNB1 promoting Wnt signaling (PubMed:25266658, PubMed:33964137). Plays a critical role in the regulation of nuclear lamina (PubMed:33964137). Modulates synaptic activity and brain functions by promoting degradation of AMPA receptor subunits GRIA1 and GRIA2. The RNF220/ZC4H2 complex monoubiquitinates PHOX2A and PHOX2B to enhance their DNA-binding ability and transactivity (By similarity). Promotes 'Lys-63'-linked polyubiquitination of Gli transcriptional activators and repressors, facilitating their nuclear export by CRM1 to fine-tune the sonic hedgehog/Gli signaling (By similarity). Regulates type I and type II interferon responses upon viral or bacterial infection by mediating 'Lys-63'-linked polyubiquitination of STAT1 (PubMed:32814877). Also regulates STAT3 phosphorylation, nuclear translocation, and transcriptional activity via ubiquitination (PubMed:41219491). Promotes OLIG1 and OLIG2 'Lys-63'-linked polyubiquitination and stabilization, two master regulatory transcription factors involved in oligodendroglial development (PubMed:38324685)