RNF34

protein-coding

ring finger protein 34, the group of Ring finger proteins

Gene summary

The protein encoded by this gene contains a RINF finger, a motif known to be involved in protein-protein and protein-DNA interactions. This protein interacts with DNAJA3/hTid-1, which is a DnaJ protein reported to function as a modulator of apoptosis. Overexpression of this gene in Hela cells was shown to confer the resistance to TNF-alpha induced apoptosis, suggesting an anti-apoptotic function of this protein. This protein can be cleaved by caspase-3 during the induction of apoptosis. This protein also targets p53 and phospho-p53 for degradation. Alternatively splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]

MANE transcript

NM_025126.4

Inheritance

—

ClinVar variants

U:41B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr12:121,400,083-121,430,623

External References & Databases

Ensembl (ENSG00000170633)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 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 RNF34 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025126.4. 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				2 clinvar		2
missense			41 clinvar	3 clinvar	1 clinvar	45
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	41	5	1	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025126.4	RefSeq	NP_079402.2	6	MANE Select
ENST00000361234.10	Ensembl	ENSP00000355137.5	6	MANE Select
NM_001256858.2	RefSeq	NP_001243787.1	5	Standard
NM_001394208.1	RefSeq	NP_001381137.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription
Immune System
Adaptive Immune System

Biological Process

ubiquitin-dependent protein catabolic process
apoptotic process
protein ubiquitination
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
proteasome-mediated ubiquitin-dependent protein catabolic process

Molecular Function

p53 binding
protein binding
ubiquitin protein ligase binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392465
Coding exons: 6
Length: 30546
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.44	159	219	0.726	0.0000133	2434
Missense (PolyPhen)		60	103.8	0.57802		1089
Synonymous	0.751	78	86.9	0.897	0.00000570	719
Loss of Function	3.01	3	16.0	0.188	7.61e-7	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis (PubMed:15069192). May mediate 'Lys-48'-linked polyubiquitination of RIPK1 and its subsequent proteasomal degradation thereby indirectly regulating the tumor necrosis factor-mediated signaling pathway (Ref.13). Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation (PubMed:17121812). Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN (PubMed:18382127). Mediates PPARGC1A proteasomal degradation probably through ubiquitination thereby indirectly regulating the metabolism of brown fat cells (PubMed:22064484). Possibly involved in innate immunity, through 'Lys-48'-linked polyubiquitination of NOD1 and its subsequent proteasomal degradation (PubMed:25012219). {ECO:0000269|PubMed:12118383, ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:15897238, ECO:0000269|PubMed:17121812, ECO:0000269|PubMed:22064484, ECO:0000269|PubMed:25012219, ECO:0000269|Ref.13, ECO:0000303|PubMed:18382127}.;

Recessive Scores

pRec: 0.160

Intolerance Scores

LoFtool: 0.642
RVIS EVS: -0.34
RVIS percentile EVS: 30.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.627

Gene Damage Prediction

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