RNF19A

protein-coding

ring finger protein 19A, RBR E3 ubiquitin protein ligase, the group of Ring finger proteins|RBR E3 ubiquitin ligases

Gene summary

This gene encodes a member of the ring between ring fingers (RBR) protein family, and the encoded protein contains two RING-finger motifs and an in between RING fingers motif. This protein is an E3 ubiquitin ligase that is localized to Lewy bodies, and ubiquitylates synphilin-1, which is an interacting protein of alpha synuclein in neurons. The encoded protein may be involved in amyotrophic lateral sclerosis and Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Previous symbols:

RNF19

MANE transcript

NM_183419.4

Inheritance

—

ClinVar variants

U:81B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr8:100,257,060-100,336,218

External References & Databases

Ensembl (ENSG00000034677)

Transcript & Mutation Effects

hg38 • Region Span ~79.2 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 RNF19A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_183419.4. 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			3 clinvar		1 clinvar	4
missense			76 clinvar	2 clinvar		78
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	81	2	1	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_183419.4	RefSeq	NP_904355.1	9	MANE Select
ENST00000341084.7	Ensembl	ENSP00000342667.2	9	MANE Select
NM_001280539.2	RefSeq	NP_001267468.1	9	Standard
NM_001353837.2	RefSeq	NP_001340766.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Parkin-Ubiquitin Proteasomal System pathway
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

protein polyubiquitination
microtubule cytoskeleton organization
ubiquitin-dependent protein catabolic process
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
regulation of protein catabolic process at postsynapse, modulating synaptic transmission

Molecular Function

ubiquitin-protein transferase activity
transcription factor binding
ubiquitin conjugating enzyme binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

ubiquitin ligase complex
cytoplasm
centrosome
cytosol
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000519449
Coding exons: 9
Length: 79159
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.38	322	467	0.690	0.0000245	5547
Missense (PolyPhen)		77	167.46	0.45981		1918
Synonymous	-0.0636	158	157	1.01	0.00000799	1608
Loss of Function	4.00	10	35.9	0.279	0.00000226	421

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00018	0.00016	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR. Specifically ubiquitinates pathogenic SOD1 variants, which leads to their proteasomal degradation and to neuronal protection. {ECO:0000269|PubMed:11237715, ECO:0000269|PubMed:12145308, ECO:0000269|PubMed:12750386, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16513638}.;

Recessive Scores

pRec: 0.144

Intolerance Scores

LoFtool: 0.0865
RVIS EVS: -0.82
RVIS percentile EVS: 11.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.914

Gene Damage Prediction

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