RNF41

Summary

RNF41 (ring finger protein 41, HGNC:18401) is a protein-coding gene on chromosome 12q13.3, encoding E3 ubiquitin-protein ligase NRDP1 (Q9H4P4). Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins.

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.

Source: NCBI Gene 10193 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_005785

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18401
Approved symbol	RNF41
Name	ring finger protein 41
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SBBI03, NRDP1
Ensembl gene	ENSG00000181852
Ensembl biotype	protein_coding
OMIM	620051
Entrez	10193

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000345093, ENST00000394013, ENST00000547967, ENST00000548120, ENST00000548225, ENST00000549038, ENST00000549119, ENST00000550379, ENST00000551711, ENST00000552244, ENST00000552656, ENST00000615206, ENST00000881816, ENST00000881817, ENST00000881818, ENST00000881819, ENST00000881820, ENST00000881821, ENST00000881822, ENST00000922432, ENST00000922433, ENST00000959116, ENST00000959117, ENST00000959118

RefSeq mRNA: 4 — MANE Select: NM_005785 NM_001242826, NM_005785, NM_194358, NM_194359

CCDS: CCDS8909, CCDS8910

Canonical transcript exons

ENST00000345093 — 7 exons

Exon	Start	End
ENSE00001274782	56208163	56208298
ENSE00001274827	56202179	56206798
ENSE00001343359	56216429	56216613
ENSE00001517253	56221760	56221922
ENSE00003564994	56210297	56210568
ENSE00003656391	56207646	56207749
ENSE00003685404	56213958	56214070

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 95.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.4376 / max 100.4753, expressed in 1801 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131495	8.5161	1772
131494	7.9215	1712

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	95.55	gold quality
paraflocculus	UBERON:0005351	94.73	gold quality
cortical plate	UBERON:0005343	94.32	gold quality
frontal pole	UBERON:0002795	94.26	gold quality
prefrontal cortex	UBERON:0000451	93.36	gold quality
islet of Langerhans	UBERON:0000006	92.38	gold quality
monocyte	CL:0000576	92.27	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.06	gold quality
mononuclear cell	CL:0000842	92.02	gold quality
stromal cell of endometrium	CL:0002255	91.97	gold quality
leukocyte	CL:0000738	91.93	gold quality
gall bladder	UBERON:0002110	91.45	gold quality
right coronary artery	UBERON:0001625	91.38	gold quality
frontal cortex	UBERON:0001870	91.02	gold quality
neocortex	UBERON:0001950	90.55	gold quality
popliteal artery	UBERON:0002250	90.46	gold quality
tibial artery	UBERON:0007610	90.46	gold quality
thoracic aorta	UBERON:0001515	90.43	gold quality
aorta	UBERON:0000947	90.34	gold quality
ascending aorta	UBERON:0001496	90.34	gold quality
cerebellar cortex	UBERON:0002129	90.19	gold quality
cerebellar hemisphere	UBERON:0002245	90.13	gold quality
cerebellum	UBERON:0002037	90.12	gold quality
descending thoracic aorta	UBERON:0002345	90.06	gold quality
left adrenal gland cortex	UBERON:0035825	89.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.94	gold quality
left adrenal gland	UBERON:0001234	89.91	gold quality
left coronary artery	UBERON:0001626	89.90	gold quality
ganglionic eminence	UBERON:0004023	89.83	gold quality
mucosa of stomach	UBERON:0001199	89.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	398.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting RNF41, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AB	99.95	71.31	3488

Literature-anchored findings (GeneRIF, showing 34)

• Nrdp1 can be important in the initiation of apoptosis by catalyzing ubiquitination and degradation of BRUCE. (PMID:14765125)
• Results indicate that Nrdp1 is a specific target for the USP8 deubiquitinating enzyme and are consistent with a model where USP8 augments Nrdp1 activity by mediating its stabilization (PMID:15314180)
• The USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a conserved peptide loop of the rhodanese domain. (PMID:17035239)
• Neuregulin 1-induced protein stability cascade involving USP8 and Nrdp1 mediates the down-regulation of ErbB3 (PMID:17210635)
• This study do not support the hypothesis of a major role for the Nrdp1 gene in PD development in the Chinese population. (PMID:19800834)
• RNF41 mRNA measured by real time reverse-transcriptase polymerase chain reaction reaction quantifies heart allograft apoptosis in graft rejection. (PMID:20098290)
• Observations point to a model of CRPC development in which progression of PCa to castration resistance is associated with the inability of AR to transcriptionally regulate Nrdp1, and predict that inhibition of ErbB3 during AW may impair CRPC development. (PMID:20587519)
• Post-transcriptional mechanisms contribute to the suppression of the ErbB3 negative regulator protein Nrdp1 in mammary tumors. (PMID:20628057)
• RNF41 interacts with JAK2-associated cytokine receptor complexes and modulates their cell surface exposure and signalling. (PMID:21378310)
• Data demonstrate that Nrdp1 preferentially associates with the nascent form of ErbB3 to accelerate its degradation, and that the two proteins colocalize at the endoplasmic reticulum. (PMID:21576364)
• these data provide insights into understanding the potential role of Nrdp1 in cell growth, apoptosis and oxidative stress, and in the pathogenesis of Parkinson’s disease. (PMID:21693106)
• Balanced reciprocal cross-regulation of RNF41 and USP8 determines whether receptors are sorted for lysosomal degradation or recycling, this way regulating basal cytokine receptor levels. (PMID:23750007)
• Phosphorylation of RNF41 by Par-1b regulates basolateral membrane targeting of laminin-111 receptors. (PMID:24259665)
• Coiled-coil domain deletion abrogates Nrdp1 oligomerization and suppresses Nrdp1 but not ErbB3 ubiquitination and degradation. (PMID:24519943)
• Lower expression of Nrdp1 in human glioma contributes tumor progression by reducing apoptosis. (PMID:25355637)
• Nrdp1 may serve as a useful biomarker for the clinical outcome and efficacy of adjuvant anthracyclines-based chemotherapy in breast cancer. (PMID:25519010)
• The results of this study suggested that Nrdp1-mediated ErbB3 degradation suppresses glioma migration and invasion and that loss of Nrdp1 may amplify ErbB3 signaling to contribute to glioma migration and invasion. (PMID:26088461)
• ABPN downregulates multiple components of the EGFR/ErbB3 signaling pathway through Nrdp1 activation. (PMID:26464195)
• Nrdp1S is a tumour suppressor that which potentiates the Nrdp1-mediated ubiquitination and degradation of ErbB3. An Nrdp1S deficiency may also be an important factor in the loss of Nrdp1. (PMID:26612725)
• findings suggest that HBx promotes the progression of hepatocellular carcinoma by decreasing the stability of Nrdp1, which results in up-regulation of ErbB3 (PMID:26846102)
• HPV 16 E2 can modulate ErbB-3 by interacting with Nrdp-1, which is involved in the regulation of this receptor, via ubiquitination and degradation. (PMID:26963794)
• the association between RNF41 polymorphisms and congenital heart disease in the Chinese Mongolian population (PMID:27323192)
• Results show low expression level of NRDP1 in colorectal neoplasm independently of tumor stage. (PMID:27648936)
• Authors conclude that the planar cell polarity (PCP) pathway contributes significantly to the motility and hence the invasiveness of glioblastoma multiforme (GBM) cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. (PMID:28481871)
• Data suggest that PHLPP1 plays an important role in assembly of kinetochores by counteracting RNF41-mediated SGT1 degradation. (PHLPP1 = PH domain and leucine rich repeat protein phosphatase 1; RNF41 = ring finger protein 41; SGT1 = suppressor of G2 allele of SKP1) (PMID:28696259)
• Over-expression of miR-497 promotes the proliferation of glioma cells U87 by targeting Nrdp1. (PMID:28871945)
• Data (including data from studies using knockout and transgenic mice/cells) suggest that CLEC16A, NRDP1, and USP8 form tripartite complex; CLEC16A-NRDP1-USP8 complex appears to rely on ubiquitin signals to promote mitophagy and maintain mitochondrial function necessary for beta-cell function. (CLEC16A = C-type lectin domain family 16 member A; NRDP1 = ubiquitin-protein ligase NRDP1; USP8 = ubiquitin specific peptidase 8) (PMID:29180353)
• RNF41 is essential to IFNI pathway activation in order to maintain muscle insulin sensitivity during human obesity. (PMID:29410345)
• Low HER3 expression is suggested to be a valuable prognostic biomarker to predict recurrence in HER2-amplified breast cancer. (PMID:30367623)
• Genome-wide association study in the Taiwan Biobank identifies four novel genes for human height: NABP2, RASA2, RNF41 and SLC39A5. (PMID:34270706)
• m[6]A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation. (PMID:36446779)
• Correlation between neuregulin receptor degradation protein-1 and Crohn’s disease. (PMID:38583443)
• VEGF-induced Nrdp1 deficiency in vascular endothelial cells promotes cancer metastasis by degrading vascular basement membrane. (PMID:38654108)
• A noncanonical E3 ubiquitin ligase RNF41-mediated MYO1C stability promotes prostate cancer metastasis by inducing actin remodeling. (PMID:39112516)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf41	ENSDARG00000036831
mus_musculus	Rnf41	ENSMUSG00000025373
rattus_norvegicus	Rnf41	ENSRNOG00000086706
drosophila_melanogaster	elgi	FBGN0283649

Paralogs (1): RNF151 (ENSG00000179580)

Protein

Protein identifiers

E3 ubiquitin-protein ligase NRDP1 — Q9H4P4 (reviewed: Q9H4P4)

Alternative names: RING finger protein 41, RING-type E3 ubiquitin transferase NRDP1

All UniProt accessions (6): Q9H4P4, F8VNZ6, F8VSB6, F8VSE5, F8VSP7, F8VVY2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88. Negatively regulates MYD88-dependent production of pro-inflammatory cytokines. Can promote TRIF-dependent production of type I interferon and inhibits infection with vesicular stomatitis virus. 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. 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. Also acts 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.

Subunit / interactions. Interacts with USP8, ERBB3, PRKN and BIRC6. Interacts with CSF2RB, EPOR, IL3RA, MYD88 and TBK1. Interacts with CLEC16A.

Tissue specificity. Detected in ovary, testis and prostate.

Post-translational modifications. Autoubiquitinated. Autoubiquitination leads to proteasomal degradation. Deubiquitinated by USP8 to get stabilized which induces apoptosis.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H4P4-1	1	yes
Q9H4P4-2	2

RefSeq proteins (4): NP_001229755, NP_005776, NP_919339, NP_919340 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013010	Znf_SIAH	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR015036	NRDP1	Domain
IPR017907	Znf_RING_CS	Conserved_site
IPR037255	NRDP1_C	Homologous_superfamily

Pfam: PF08941, PF13923

UniProt features (24 total): helix 8, strand 6, turn 3, mutagenesis site 3, zinc finger region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2FZP	X-RAY DIFFRACTION	1.87
2GWF	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4P4-F1	91.97	0.79

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (3):

Position	Phenotype
34	loss of activity; when associated with q-36.
36	loss of activity; when associated with s-34.
56	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1358803	Downregulation of ERBB2:ERBB3 signaling
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1227986	Signaling by ERBB2
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-8863795	Downregulation of ERBB2 signaling
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 215 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_AUTOPHAGY, GCM_GSPT1, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOMF_GTPASE_BINDING, GCM_BCL2L1

GO Biological Process (17): protein polyubiquitination (GO:0000209), autophagy (GO:0006914), negative regulation of cell population proliferation (GO:0008285), proteasomal protein catabolic process (GO:0010498), negative regulation of cell migration (GO:0030336), regulation of MAPK cascade (GO:0043408), regulation of lymphocyte differentiation (GO:0045619), regulation of myeloid cell differentiation (GO:0045637), positive regulation of protein catabolic process (GO:0045732), protein autoubiquitination (GO:0051865), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), extrinsic apoptotic signaling pathway (GO:0097191), negative regulation of mitophagy (GO:1901525), regulation of reactive oxygen species metabolic process (GO:2000377), positive regulation of reactive oxygen species metabolic process (GO:2000379), apoptotic process (GO:0006915), protein ubiquitination (GO:0016567)

GO Molecular Function (13): ubiquitin-protein transferase activity (GO:0004842), erythropoietin receptor binding (GO:0005128), interleukin-3 receptor binding (GO:0005135), zinc ion binding (GO:0008270), protein domain specific binding (GO:0019904), receptor tyrosine kinase binding (GO:0030971), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum tubular network (GO:0071782)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Downregulation of ERBB2 signaling	1
Class I MHC mediated antigen processing & presentation	1
Signaling by Receptor Tyrosine Kinases	1
Immune System	1
Signaling by ERBB2	1
Signal Transduction	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
protein ubiquitination	2
protein catabolic process	2
regulation of intracellular signal transduction	2
apoptotic signaling pathway	2
reactive oxygen species metabolic process	2
cytokine receptor binding	2
cytoplasm	2
cellular anatomical structure	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
MAPK cascade	1
lymphocyte differentiation	1
regulation of lymphocyte activation	1
regulation of leukocyte differentiation	1
myeloid cell differentiation	1
regulation of hemopoiesis	1
positive regulation of catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
cell surface receptor signaling pathway	1
mitophagy	1
negative regulation of macroautophagy	1
regulation of mitophagy	1
negative regulation of autophagy of mitochondrion	1
regulation of metabolic process	1
positive regulation of metabolic process	1
regulation of reactive oxygen species metabolic process	1
programmed cell death	1
execution phase of apoptosis	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1

Protein interactions and networks

STRING

1776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF41	USP8	P40818	992
RNF41	CLEC16A	Q2KHT3	851
RNF41	BIRC6	Q9NR09	847
RNF41	ERBB3	P21860	764
RNF41	TBK1	Q9UHD2	713
RNF41	MARK2	Q7KZI7	681
RNF41	PRKN	O60260	655
RNF41	KIF23	Q02241	644
RNF41	ERBB4	Q15303	602
RNF41	DIABLO	Q9NR28	600
RNF41	TOMM70	O94826	590
RNF41	STUB1	Q9UNE7	589
RNF41	UBE2K	P27924	553
RNF41	HTRA2	O43464	550
RNF41	FBXO2	Q9UK22	521

IntAct

181 interactions, top by confidence:

A	B	Type	Score
TTC1	RNF41	psi-mi:“MI:0915”(physical association)	0.900
RNF41	TTC1	psi-mi:“MI:0915”(physical association)	0.900
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
ASB6	RNF41	psi-mi:“MI:0915”(physical association)	0.830
RNF41	ASB6	psi-mi:“MI:0915”(physical association)	0.830
TTC1	VAPB	psi-mi:“MI:0914”(association)	0.790
RFC4	RNF41	psi-mi:“MI:0915”(physical association)	0.780
ISCA2	RNF41	psi-mi:“MI:0915”(physical association)	0.780
VPS52	RNF41	psi-mi:“MI:0915”(physical association)	0.780
RNF41	RFC4	psi-mi:“MI:0915”(physical association)	0.780
RNF41	ISCA2	psi-mi:“MI:0915”(physical association)	0.780
RNF41	VPS52	psi-mi:“MI:0915”(physical association)	0.780
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
RNF41	ENOPH1	psi-mi:“MI:0915”(physical association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730

BioGRID (306): RNF41 (Two-hybrid), RNF41 (Two-hybrid), RNF41 (Two-hybrid), RNF41 (Two-hybrid), RNF41 (Two-hybrid), ARL6IP4 (Two-hybrid), C1orf109 (Two-hybrid), LZTS2 (Two-hybrid), ISCA2 (Two-hybrid), ASB6 (Two-hybrid), RNF41 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), RFC4 (Two-hybrid)

ESM2 similar proteins: A0JP89, A8WZU5, B6VQ60, E0VIU9, G2TRS9, O55735, O55765, P0CY10, P0CY11, P23801, P24647, P32512, P36113, P41454, P41455, P90740, Q03605, Q04149, Q04511, Q04638, Q09623, Q11072, Q197D9, Q23243, Q2NNU1, Q54C11, Q5FWL3, Q5R7T5, Q5UPT1, Q5UQ40, Q6GMD3, Q708A1, Q7ZW16, Q85318, Q8B9B2, Q8BH75, Q90173, Q91FJ2, Q91FL1, Q91G88

Diamond homologs: A0A1L8FG46, A0A8C0TYJ0, D3YY23, E7FDW2, F1MAD2, G2Q0E2, O14907, O14910, O35274, O35867, O55164, O60106, O88951, O88952, P31007, P57105, P68907, Q00940, Q05568, Q09506, Q0P5E6, Q0P5F3, Q0V8R5, Q12959, Q13424, Q13425, Q13884, Q1L5Z9, Q22638, Q28626, Q2KHN1, Q2KIB6, Q2TBT8, Q32LM6, Q3T0C9, Q5F425, Q5FWL3, Q5PYH6, Q5R7T5, Q5RAA5

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
USP8	“up-regulates quantity by stabilization”	RNF41	deubiquitination
RNF41	“down-regulates quantity by destabilization”	USP8	ubiquitination
Ub:E2	“up-regulates activity”	RNF41	ubiquitination
RNF41	“down-regulates quantity by destabilization”	ERBB3	polyubiquitination
RNF41	“down-regulates quantity by destabilization”	PRKN	polyubiquitination
RNF41	“down-regulates quantity by destabilization”	VPS52	ubiquitination
RNF41	“down-regulates quantity by destabilization”	PRKN	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Negative regulation of the PI3K/AKT network	5	17.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

32 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1165 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56207576:T:A	donor_gain	1.0000
12:56207629:T:TA	donor_gain	1.0000
12:56207637:GACAC:G	donor_loss	1.0000
12:56207638:ACAC:A	donor_loss	1.0000
12:56207639:CACT:C	donor_loss	1.0000
12:56207640:AC:A	donor_loss	1.0000
12:56207641:CT:C	donor_loss	1.0000
12:56207642:TCACT:T	donor_loss	1.0000
12:56207643:CAC:C	donor_loss	1.0000
12:56207644:A:AC	donor_gain	1.0000
12:56207644:ACTC:A	donor_loss	1.0000
12:56207645:C:CT	donor_gain	1.0000
12:56207645:CT:C	donor_gain	1.0000
12:56207645:CTCT:C	donor_gain	1.0000
12:56207745:CGCTT:C	acceptor_gain	1.0000
12:56207747:CTT:C	acceptor_gain	1.0000
12:56207748:TT:T	acceptor_gain	1.0000
12:56207748:TTCTG:T	acceptor_loss	1.0000
12:56207749:TC:T	acceptor_loss	1.0000
12:56207750:C:CA	acceptor_loss	1.0000
12:56207750:C:CC	acceptor_gain	1.0000
12:56207752:G:C	acceptor_gain	1.0000
12:56207753:T:C	acceptor_gain	1.0000
12:56207753:T:TC	acceptor_gain	1.0000
12:56207755:G:C	acceptor_gain	1.0000
12:56207755:G:GC	acceptor_gain	1.0000
12:56208157:GCCTA:G	donor_loss	1.0000
12:56208158:CCTAC:C	donor_loss	1.0000
12:56208159:CTA:C	donor_loss	1.0000
12:56208160:TA:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000383382 (12:56218195 C>T), RS1000585678 (12:56221599 T>C), RS1000639034 (12:56214829 A>T), RS1000701340 (12:56215252 C>T), RS1000991781 (12:56205862 A>G), RS1001107923 (12:56205574 G>C), RS1001123944 (12:56221792 T>C), RS1001154393 (12:56218194 T>C), RS1001265795 (12:56212368 T>C), RS1001326113 (12:56204653 C>A,T), RS1001524571 (12:56214475 G>A), RS1001565340 (12:56218453 G>C), RS1001610467 (12:56204919 A>G), RS1001718671 (12:56212046 G>A,C), RS1002043517 (12:56221266 T>C)

Disease associations

OMIM: gene MIM:620051 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008916_124	Asthma	1.000000e-16
GCST011972_41	Height	2.000000e-33

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
K 7174	increases expression	1
Sunitinib	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Naphthoquinones	increases expression	1
Silicon Dioxide	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2E0	Abcam HeLa RNF41 KO	Cancer cell line	Female
CVCL_TJ38	HAP1 RNF41 (-) 1	Cancer cell line	Male
CVCL_TJ39	HAP1 RNF41 (-) 2	Cancer cell line	Male
CVCL_TJ40	HAP1 RNF41 (-) 3	Cancer cell line	Male
CVCL_TJ41	HAP1 RNF41 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.