RNF180

protein-coding

ring finger protein 180, the group of Ring finger proteins

Gene summary

Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Predicted to be involved in norepinephrine metabolic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and serotonin metabolic process. Predicted to act upstream of or within several processes, including adult behavior; positive regulation of protein ubiquitination; and protein polyubiquitination. Predicted to be located in nuclear envelope. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001113561.2

Inheritance

—

ClinVar variants

U:77B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr5:64,165,843-64,372,869

External References & Databases

Ensembl (ENSG00000164197)

Transcript & Mutation Effects

hg38 • Region Span ~207.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNF180 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 82

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001113561.2. 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						0
missense			76 clinvar	8 clinvar		84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	77	8	0	85

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001113561.2	RefSeq	NP_001107033.1	7	MANE Select
ENST00000389100.9	Ensembl	ENSP00000373752.4	7	MANE Select
NM_001323291.1	RefSeq	NP_001310220.1	3	Standard
NM_001323292.2	RefSeq	NP_001310221.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein polyubiquitination
adult behavior
positive regulation of protein ubiquitination
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
norepinephrine metabolic process

Molecular Function

ubiquitin conjugating enzyme binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

nuclear envelope
integral component of membrane
intrinsic component of endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389100
Coding exons: 7
Length: 207026
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125745
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.624	257	287	0.896	0.0000141	3922
Missense (PolyPhen)		16	20.687	0.77345		262
Synonymous	0.0902	100	101	0.989	0.00000478	1080
Loss of Function	2.18	13	24.7	0.526	0.00000132	337

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00027	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.00033	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase which promotes polyubiquitination and degradation by the proteasome pathway of ZIC2. {ECO:0000250|UniProtKB:Q3U827}.;

Recessive Scores

pRec: 0.0769

Intolerance Scores

LoFtool: 0.268
RVIS EVS: 0.11
RVIS percentile EVS: 61.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.626

Gene Damage Prediction

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