RNF41

protein-coding

ring finger protein 41, the group of Ring finger proteins

Gene summary

This gene encodes an E3 ubiquitin ligase. The encoded protein plays a role in type 1 cytokine receptor signaling by controlling the balance between JAK2-associated cytokine receptor degradation and ectodomain shedding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]

MANE transcript

NM_005785.4

Inheritance

—

ClinVar variants

U:18B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr12:56,202,179-56,221,933

External References & Databases

Ensembl (ENSG00000181852)

Transcript & Mutation Effects

hg38 • Region Span ~19.8 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 RNF41 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 16

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005785.4. 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	1 clinvar	2
missense			17 clinvar		1 clinvar	18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	18	1	2	21

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005785.4	RefSeq	NP_005776.1	5	MANE Select
ENST00000345093.9	Ensembl	ENSP00000342755.4	5	MANE Select
NM_001242826.2	RefSeq	NP_001229755.1	5	Standard
NM_194358.3	RefSeq	NP_919339.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rnf41	Danio rerio	Structure: melanocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

rnf41

Danio rerio

Structure: melanocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Regulation of toll-like receptor signaling pathway
Signal Transduction
neuroregulin receptor degredation protein-1 controls erbb3 receptor recycling
Immune System

Biological Process

protein polyubiquitination
autophagy
negative regulation of cell population proliferation
proteasomal protein catabolic process
negative regulation of cell migration

Molecular Function

ubiquitin-protein transferase activity
erythropoietin receptor binding
interleukin-3 receptor binding
protein binding
zinc ion binding

Cellular Component

cytosol
perinuclear region of cytoplasm
endoplasmic reticulum tubular network

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000345093
Coding exons: 5
Length: 17433
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125743
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.00	85	206	0.413	0.0000132	2098
Missense (PolyPhen)		10	47.527	0.21041		523
Synonymous	-0.0813	76	75.1	1.01	0.00000484	615
Loss of Function	3.36	1	15.1	0.0661	8.18e-7	153

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88. Negatively regulates MYD88-dependent production of proinflammatory cytokines. Can promote TRIF-dependent production of type I interferon and inhibits infection with vesicular stomatitis virus (By similarity). Promotes also activation of TBK1 and IRF3. Involved in the ubiquitination of erythropoietin (EPO) and interleukin-3 (IL-3) receptors. Thus, through maintaining basal levels of cytokine receptors, RNF41 is involved in the control of hematopoietic progenitor cell differentiation into myeloerythroid lineages (By similarity). Contributes to the maintenance of steady-state ERBB3 levels by mediating its growth factor- independent degradation. Involved in the degradation of the inhibitor of apoptosis BIRC6 and thus is an important regulator of cell death by promoting apoptosis. Acts also as a PRKN modifier that accelerates its degradation, resulting in a reduction of PRKN activity, influencing the balance of intracellular redox state. The RNF41-PRKN pathway regulates autophagosome-lysosome fusion during late mitophagy. Mitophagy is a selective form of autophagy necessary for mitochondrial quality control (PubMed:24949970). {ECO:0000250, ECO:0000250|UniProtKB:Q8BH75, ECO:0000269|PubMed:12411582, ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:15632191, ECO:0000269|PubMed:17210635, ECO:0000269|PubMed:18541373, ECO:0000269|PubMed:19483718, ECO:0000269|PubMed:24949970}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

LoFtool: 0.148
RVIS EVS: -0.16
RVIS percentile EVS: 41.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.985

Gene Damage Prediction

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