RNF220

protein-coding

ring finger protein 220, the group of MicroRNA protein coding host genes|Ring finger proteins

Gene summary

Enables beta-catenin binding activity and ubiquitin protein ligase activity. Involved in positive regulation of canonical Wnt signaling pathway and protein polyubiquitination. Acts upstream of or within positive regulation of transcription by RNA polymerase II and protein monoubiquitination. Located in nuclear lamina and nucleoplasm. Part of protein-containing complex. Implicated in hypomyelinating leukodystrophy 23. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C1orf164

MANE transcript

NM_018150.4

Inheritance

ClinVar variants

P:2U:71B:7

Top phenotype

Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr1:44,405,194-44,651,723

External References & Databases

Ensembl (ENSG00000187147)

Transcript & Mutation Effects

hg38 • Region Span ~246.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030514

Submitter: Labcorp Genetics (formerly Invitae)

leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030514

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathyAR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Neurologic

Intervention: Cardiovascular

Rationale: Among other features, the condition may include cardiomyopathy, and awareness may allow early management of this issue

Refs: 33964137

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNF220 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 4

Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathyTotal: 3

RNF220-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018150.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	7 clinvar		8
missense	2 clinvar		64 clinvar			66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	2	0	71	7	0	80

Highest pathogenic variant AF is 0.000006207155

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018150.4	RefSeq	NP_060620.2	14	MANE Select
ENST00000361799.7	Ensembl	ENSP00000354872.2	14	MANE Select
NM_001319956.1	RefSeq	NP_001306885.1	14	Standard
NM_001319957.2	RefSeq	NP_001306886.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

protein ubiquitination
protein autoubiquitination
positive regulation of canonical Wnt signaling pathway

Molecular Function

ubiquitin-protein transferase activity
protein binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355387
Coding exons: 14
Length: 246531
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125746
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.22	234	351	0.666	0.0000214	3696
Missense (PolyPhen)		70	134.08	0.52207		1318
Synonymous	0.0200	137	137	0.998	0.00000840	1128
Loss of Function	4.84	2	31.1	0.0643	0.00000160	339

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of SIN3B (By similarity). Independently of its E3 ligase activity, acts as a CTNNB1 stabilizer through USP7-mediated deubiquitination of CTNNB1 promoting Wnt signaling (PubMed:25266658). {ECO:0000250|UniProtKB:Q6PDX6, ECO:0000269|PubMed:25266658}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.0531
RVIS EVS: -0.65
RVIS percentile EVS: 16.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.943

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium