RNF181

protein-coding

ring finger protein 181, the group of Ring finger proteins

Gene summary

RNF181 binds the integrin alpha-IIb (ITGA2B; MIM 607759)/beta-3 (ITGB3; MIM 173470) complex and has E3 ubiquitin ligase activity (Brophy et al., 2008 [PubMed 18331836]).[supplied by OMIM, Dec 2008]

MANE transcript

NM_016494.4

Inheritance

—

ClinVar variants

U:20B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.18

Max pathogenic AF

—

Genomic locus

chr2:85,595,725-85,597,708

External References & Databases

Ensembl (ENSG00000168894)

Transcript & Mutation Effects

hg38 • Region Span ~2.0 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 RNF181 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 18

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016494.4. 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						0
missense			18 clinvar	1 clinvar		19
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	20	2	0	22

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016494.4	RefSeq	NP_057578.1	5	MANE Select
ENST00000306368.9	Ensembl	ENSP00000306906.4	5	MANE Select
ENST00000414390.5	Ensembl	ENSP00000397109.1	3	Standard
ENST00000441634.5	Ensembl	ENSP00000412025.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Protein ubiquitination
E3 ubiquitin ligases ubiquitinate target proteins

Biological Process

protein ubiquitination
protein autoubiquitination

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: ENST00000306368
Coding exons: 5
Length: 1889
Individuals with no LoFs: 125667
Homozygous LoFs: 0
Heterozygous LoFs: 81
Defined: 125748
p: 0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.483	74	86.7	0.854	0.00000434	1008
Missense (PolyPhen)		14	26.547	0.52736		309
Synonymous	0.945	27	34.0	0.794	0.00000176	274
Loss of Function	-0.523	12	10.2	1.18	5.99e-7	100

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00044	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0021	0.0021	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. {ECO:0000269|PubMed:18331836}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.573
RVIS EVS: 0.28
RVIS percentile EVS: 71.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.200