RNF5

Summary

RNF5 (ring finger protein 5, HGNC:10068) is a protein-coding gene on chromosome 6p21.32, encoding E3 ubiquitin-protein ligase RNF5 (Q99942). Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins.

The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions.

Source: NCBI Gene 6048 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 11 total
• Druggable target: yes
• MANE Select transcript: NM_006913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10068
Approved symbol	RNF5
Name	ring finger protein 5
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	NG2, G16, RING5, RMA1
Ensembl gene	ENSG00000204308
Ensembl biotype	protein_coding
OMIM	602677
Entrez	6048

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375094, ENST00000487940, ENST00000876421, ENST00000876422, ENST00000876423, ENST00000876424, ENST00000876425, ENST00000921946

RefSeq mRNA: 1 — MANE Select: NM_006913 NM_006913

CCDS: CCDS4745

Canonical transcript exons

ENST00000375094 — 6 exons

Exon	Start	End
ENSE00001628867	32179877	32179931
ENSE00001741203	32180009	32180126
ENSE00001791691	32179651	32179763
ENSE00001850999	32180229	32180793
ENSE00002314392	32178405	32178651
ENSE00003603513	32179541	32179559

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8606 / max 215.3042, expressed in 1772 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67120	10.5044	1725
67121	1.7487	1100
203954	1.0310	657
203955	0.3850	186
67122	0.1915	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.49	gold quality
adult mammalian kidney	UBERON:0000082	97.21	gold quality
cortical plate	UBERON:0005343	97.04	gold quality
ventricular zone	UBERON:0003053	96.92	gold quality
right adrenal gland	UBERON:0001233	96.80	gold quality
mucosa of transverse colon	UBERON:0004991	96.78	gold quality
right adrenal gland cortex	UBERON:0035827	96.77	gold quality
monocyte	CL:0000576	96.67	gold quality
apex of heart	UBERON:0002098	96.52	gold quality
leukocyte	CL:0000738	96.51	gold quality
heart left ventricle	UBERON:0002084	96.40	gold quality
duodenum	UBERON:0002114	96.38	gold quality
right lobe of liver	UBERON:0001114	96.31	gold quality
metanephros cortex	UBERON:0010533	96.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.28	gold quality
left adrenal gland	UBERON:0001234	96.22	gold quality
putamen	UBERON:0001874	96.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.15	gold quality
rectum	UBERON:0001052	96.11	gold quality
liver	UBERON:0002107	96.09	gold quality
left adrenal gland cortex	UBERON:0035825	96.01	gold quality
kidney	UBERON:0002113	95.94	gold quality
caudate nucleus	UBERON:0001873	95.90	gold quality
temporal lobe	UBERON:0001871	95.85	gold quality
amygdala	UBERON:0001876	95.85	gold quality
nucleus accumbens	UBERON:0001882	95.82	gold quality
cortex of kidney	UBERON:0001225	95.79	gold quality
heart	UBERON:0000948	95.73	gold quality
adrenal gland	UBERON:0002369	95.56	gold quality
transverse colon	UBERON:0001157	95.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting RNF5, 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-12118	100.00	65.88	1270
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6134	99.63	65.68	1537

Literature-anchored findings (GeneRIF, showing 22)

• RNF5 regulates cell motility by targeting paxillin ubiquitination and altered localization (PMID:12861019)
• the G(16)-mediated activation of IKK/NFkappaB by N(6)-cyclohexyladenosine requires a complex signaling network composed of multiple intermediates (PMID:15485865)
• efficient bacterial escape into the cytosol of epithelial cells requires HsRMA1-mediated SopA ubiquitination and contributes to Salmonella-induced enteropathogenicity (PMID:16176924)
• RNF5 is a novel regulator of breast cancer progression through its effect on actin cytoskeletal alterations. (PMID:17804730)
• RNF5 associates with JAMP in the ER membrane. This association results in Ubc13-dependent RNF5-mediated noncanonical ubiquitination of JAMP. (PMID:19269966)
• E3 ubiquitin ligase RNF5 interacted with MITA in a viral-infection-dependent manner (PMID:19285439)
• JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRDeltaF508 for degradation. (PMID:21148293)
• In addition to confirming one of the top findings in the meta-analysis, TRIM26, RNF5 and HLA-DRB3 have been identified as potential candidate genes for schizophrenia. (PMID:22433715)
• Rma1, an E3 ubiquitin ligase localized in the ER membrane, is involved in Pendrin degradation (PMID:22750442)
• Our data suggest that RNF5 regulates the turnover of specific G protein-coupled receptors by ubiquitinating JAMP and preventing proteasome recruitment. (PMID:23798571)
• RNF5 is involved in the regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2. (PMID:25759021)
• we found that RNF5 is differentially expressed in human bronchial epithelia from CF vs. control patients. Our results identify RNF5 as a target for therapeutic modalities to antagonize mutant CFTR proteins. (PMID:26183966)
• Authors demonstrate that the V proteins of NDV and several other paramyxoviruses target MAVS for ubiquitin-mediated degradation through E3 ubiquitin ligase RING-finger protein 5 (RNF5). MAVS degradation leads to the inhibition of the downstream IFN-beta pathway and therefore benefits virus proliferation. (PMID:31270229)
• Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP. (PMID:32054686)
• Acetylation Stabilizes Phosphoglycerate Dehydrogenase by Disrupting the Interaction of E3 Ligase RNF5 to Promote Breast Tumorigenesis. (PMID:32783943)
• RING-finger protein 5 promotes hepatocellular carcinoma progression and predicts poor prognosis. (PMID:33469898)
• The E3 Ubiquitin Ligase Ring Finger Protein 5 Ameliorates NASH Through Ubiquitin-Mediated Degradation of 3-Hydroxy-3-Methylglutaryl CoA Reductase Degradation Protein 1. (PMID:34272738)
• The ubiquitin ligase RNF5 determines acute myeloid leukemia growth and susceptibility to histone deacetylase inhibitors. (PMID:34518534)
• Suppression of KSHV lytic replication and primary effusion lymphoma by selective RNF5 inhibition. (PMID:36656913)
• The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation. (PMID:36737599)
• Downregulation of EphA2 stability by RNF5 limits its tumor-suppressive function in HER2-negative breast cancers. (PMID:37816703)
• Human gastric cancer progression and stabilization of ATG2B through RNF5 binding facilitated by autophagy-associated CircDHX8. (PMID:38866787)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	RNF5	ENSDARG00000075606
mus_musculus	Rnf5	ENSMUSG00000015478
rattus_norvegicus	Rnf5	ENSRNOG00000000438
drosophila_melanogaster	sordd1	FBGN0030693
drosophila_melanogaster	sordd2	FBGN0052581
drosophila_melanogaster	CG32847	FBGN0052847
caenorhabditis_elegans		WBGENE00004381

Paralogs (1): RNF185 (ENSG00000138942)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF5 — Q99942 (reviewed: Q99942)

Alternative names: RING finger protein 5, Ram1 homolog

All UniProt accessions (2): Q99942, A0A024RCQ4

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins. May function together with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4. Mediates ubiquitination of PXN/paxillin,thereby regulating cell motility and localization of PXN/paxillin. Catalyzes ubiquitination of Salmonella type III secreted protein sopA. Mediates the ‘Lys-63’-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD; the ubiquitination appears to involve E2 ubiquitin-conjugating enzyme UBE2N. Mediates the ‘Lys-48’-linked polyubiquitination of STING1 at ‘Lys-150’ leading to its proteasomal degradation; the ubiquitination occurs in mitochondria after viral transfection and regulates antiviral responses. Catalyzes ubiquitination and subsequent degradation of ATG4B, thereby inhibiting autophagy.

Subunit / interactions. Interacts with PXN. Interacts with Salmonella typhimurium sopA. Interacts with JKAMP. Interacts with STING1; the interaction of endogenous proteins is dependent on viral infection.

Subcellular location. Cell membrane. Mitochondrion membrane. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the RNF5 family.

RefSeq proteins (1): NP_008844* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR045103	RNF5/RNF185-like	Family

Pfam: PF13920

UniProt features (15 total): sequence conflict 4, modified residue 4, transmembrane region 2, initiator methionine 1, chain 1, mutagenesis site 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99942-F1	68.71	0.22

Functional residue map

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

Post-translational modifications (4): 2, 84, 94, 107

Mutagenesis-validated functional residues (1):

Position	Phenotype
42	loss of e3 ubiquitin-protein ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-382556	ABC-family protein mediated transport
R-HSA-5678895	Defective CFTR causes cystic fibrosis
R-HSA-901032	ER Quality Control Compartment (ERQC)
R-HSA-9931269	AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-532668	N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-597592	Post-translational protein modification
R-HSA-901042	Calnexin/calreticulin cycle

MSigDB gene sets: 197 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, ACTACCT_MIR196A_MIR196B, GOBP_VACUOLE_ORGANIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CREBP1_Q2, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MACROAUTOPHAGY, CREB_Q4

GO Biological Process (12): ubiquitin-dependent protein catabolic process (GO:0006511), response to bacterium (GO:0009617), negative regulation of autophagy (GO:0010507), protein catabolic process (GO:0030163), protein destabilization (GO:0031648), ERAD pathway (GO:0036503), transmembrane transport (GO:0055085), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), endoplasmic reticulum mannose trimming (GO:1904380), regulation of autophagosome assembly (GO:2000785), protein ubiquitination (GO:0016567)

GO Molecular Function (9): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), ubiquitin-like protein conjugating enzyme binding (GO:0044390), protein-containing complex binding (GO:0044877), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), mitochondrial membrane (GO:0031966), endoplasmic reticulum quality control compartment (GO:0044322), mitochondrion (GO:0005739), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Transport of small molecules	1
ABC transporter disorders	1
Calnexin/calreticulin cycle	1
Regulation of PD-L1(CD274) Post-translational modification	1
Post-translational protein modification	1
Asparagine N-linked glycosylation	1
Disorders of transmembrane transporters	1
Disease	1
Metabolism of proteins	1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein polyubiquitination	2
binding	2
cytoplasm	2
intracellular membrane-bounded organelle	2
organelle membrane	2
cellular anatomical structure	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
response to other organism	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
macromolecule catabolic process	1
protein metabolic process	1
regulation of protein stability	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
transport	1
cellular process	1
protein alpha-1,2-demannosylation	1
endoplasmic reticulum quality control compartment	1
autophagosome assembly	1
regulation of vacuole organization	1
regulation of organelle assembly	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
protein binding	1
enzyme binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
endomembrane system	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
mitochondrion	1

Protein interactions and networks

STRING

1133 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF5	UBE2J1	Q9Y385	988
RNF5	AMFR	P26442	951
RNF5	CFTR	P13569	898
RNF5	DERL1	Q9BUN8	893
RNF5	STUB1	Q9UNE7	891
RNF5	MARCHF6	O60337	812
RNF5	RNF139	Q8WU17	755
RNF5	STING1	Q86WV6	734
RNF5	HSPA8	P11142	721
RNF5	JKAMP	Q9P055	717
RNF5	RNF26	Q9BY78	708
RNF5	MAVS	Q7Z434	661
RNF5	PCGF3	Q3KNV8	644
RNF5	IRF3	Q14653	639
RNF5	UFD1	Q92890	637

IntAct

285 interactions, top by confidence:

A	B	Type	Score
RNF5	UBE2E3	psi-mi:“MI:0915”(physical association)	0.870
UBE2E3	RNF5	psi-mi:“MI:0915”(physical association)	0.870
RNF5	UBE2D3	psi-mi:“MI:0915”(physical association)	0.840
UBE2D3	RNF5	psi-mi:“MI:0915”(physical association)	0.840
UBE2D2	RNF5	psi-mi:“MI:0407”(direct interaction)	0.820
UBE2D2	RNF5	psi-mi:“MI:0915”(physical association)	0.820
RNF5	UBE2K	psi-mi:“MI:0915”(physical association)	0.810
UBE2K	RNF5	psi-mi:“MI:0915”(physical association)	0.810
UBE2D1	RNF5	psi-mi:“MI:0915”(physical association)	0.790
RNF5	UBE2E2	psi-mi:“MI:0915”(physical association)	0.790
RNF5	UBE2D1	psi-mi:“MI:0915”(physical association)	0.790
UBE2E2	RNF5	psi-mi:“MI:0915”(physical association)	0.790

BioGRID (248): RNF5 (Two-hybrid), RNF5 (Two-hybrid), RNF5 (Two-hybrid), SLC1A1 (Two-hybrid), UBE2D1 (Two-hybrid), UBE2D3 (Two-hybrid), UBE2E2 (Two-hybrid), ABHD16A (Two-hybrid), UBE2E3 (Two-hybrid), SEC22A (Two-hybrid), INSIG2 (Two-hybrid), UBE2D4 (Two-hybrid), SLC38A7 (Two-hybrid), UBE2W (Two-hybrid), YIPF2 (Two-hybrid)

ESM2 similar proteins: A1YFY1, A2AH22, A2T6X5, A3KPW9, A4IH17, A5D9M6, A7X5R6, E7FAG6, O35445, P46379, Q09463, Q0II22, Q13501, Q15011, Q1W1Y5, Q3KPV4, Q3V209, Q4V9Y1, Q56B11, Q5M807, Q5PRF9, Q5R5B0, Q5RBA5, Q64337, Q6DIP3, Q6MG49, Q6MGB6, Q6P135, Q6PA26, Q6PC78, Q80XS6, Q8BIG4, Q8IZL8, Q8LPN7, Q8WMN5, Q91YL2, Q99942, Q9BV68, Q9C0C7, Q9D0C1

Diamond homologs: A0A1L8FG46, A0A1L8FM16, B1AUE5, E7FDW2, O35445, O60683, O64425, P68907, P87176, Q09463, Q2KHN1, Q2TBT8, Q54S31, Q568Y3, Q5M807, Q5RFK9, Q5ZIR9, Q69ZS0, Q6PC78, Q8HXW8, Q91YT2, Q96GF1, Q99942, Q9P3U8, Q9SYU4, Q9UPQ7, Q9UUF0, Q9V8P9, O76064, P09309, Q2HJ46, Q4KLN8, Q5R4I2, Q803C1, Q80Z37, Q8VC56, Q9NS56, A2XW69, A2ZAC2, O75150

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF5	ubiquitination
RNF5	“down-regulates quantity”	PXN	ubiquitination
RNF5	“down-regulates activity”	JKAMP	ubiquitination
RNF5	“down-regulates quantity by destabilization”	STING1	ubiquitination
RNF5	“down-regulates quantity by destabilization”	MAVS	ubiquitination
HSPA8	“up-regulates activity”	RNF5	binding
RNF5	“down-regulates quantity by destabilization”	CFTR	ubiquitination
RNF5	“down-regulates quantity by destabilization”	SLC26A4	ubiquitination
RNF5	“down-regulates quantity by destabilization”	ATG4B	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	7	71.6×	9e-10
E3 ubiquitin ligases ubiquitinate target proteins	5	26.9×	5e-05
Antigen processing: Ubiquitination & Proteasome degradation	12	12.4×	9e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein K11-linked ubiquitination	5	33.2×	3e-05
protein monoubiquitination	5	29.1×	5e-05
protein K48-linked ubiquitination	8	22.9×	7e-07
protein polyubiquitination	8	15.7×	7e-06
ERAD pathway	5	15.4×	9e-04
ubiquitin-dependent protein catabolic process	9	11.3×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

682 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32179649:A:AG	acceptor_gain	1.0000
6:32179649:AGT:A	acceptor_gain	1.0000
6:32179650:G:GA	acceptor_gain	1.0000
6:32179650:GT:G	acceptor_gain	1.0000
6:32179650:GTG:G	acceptor_gain	1.0000
6:32179761:CAG:C	donor_loss	1.0000
6:32179762:AGG:A	donor_loss	1.0000
6:32179765:T:A	donor_loss	1.0000
6:32179872:CTCA:C	acceptor_loss	1.0000
6:32179873:TCAG:T	acceptor_loss	1.0000
6:32179874:CAG:C	acceptor_loss	1.0000
6:32179875:A:AG	acceptor_gain	1.0000
6:32179875:A:T	acceptor_loss	1.0000
6:32179876:G:GA	acceptor_gain	1.0000
6:32179876:GATT:G	acceptor_gain	1.0000
6:32179876:GATTA:G	acceptor_gain	1.0000
6:32179927:GAGGG:G	donor_gain	1.0000
6:32179929:GGG:G	donor_gain	1.0000
6:32179930:GG:G	donor_gain	1.0000
6:32179930:GGG:G	donor_gain	1.0000
6:32179931:GG:G	donor_gain	1.0000
6:32179932:G:A	donor_loss	1.0000
6:32179932:G:GG	donor_gain	1.0000
6:32179933:TGA:T	donor_loss	1.0000
6:32179934:GAG:G	donor_loss	1.0000
6:32180004:CCTAG:C	acceptor_loss	1.0000
6:32180005:CTAG:C	acceptor_loss	1.0000
6:32180006:TAGG:T	acceptor_loss	1.0000
6:32180007:A:AG	acceptor_gain	1.0000
6:32180007:AG:A	acceptor_gain	1.0000

AlphaMissense

1173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32178597:T:A	I29K	1.000
6:32179544:G:C	W48C	1.000
6:32179544:G:T	W48C	1.000
6:32179681:T:C	C64R	1.000
6:32178590:T:A	C27S	0.999
6:32178590:T:C	C27R	0.999
6:32178591:G:A	C27Y	0.999
6:32178591:G:C	C27S	0.999
6:32178591:G:T	C27F	0.999
6:32178597:T:C	I29T	0.999
6:32178600:G:A	C30Y	0.999
6:32178636:G:A	C42Y	0.999
6:32178639:G:A	G43D	0.999
6:32178639:G:T	G43V	0.999
6:32178643:C:A	H44Q	0.999
6:32178643:C:G	H44Q	0.999
6:32179552:T:A	L51H	0.999
6:32179653:G:C	W54C	0.999
6:32179653:G:T	W54C	0.999
6:32179681:T:A	C64S	0.999
6:32179682:G:C	C64S	0.999
6:32179690:T:A	C67S	0.999
6:32179690:T:C	C67R	0.999
6:32179691:G:A	C67Y	0.999
6:32179691:G:C	C67S	0.999
6:32179691:G:T	C67F	0.999
6:32179694:A:T	K68I	0.999
6:32178592:T:G	C27W	0.998
6:32178599:T:A	C30S	0.998
6:32178599:T:C	C30R	0.998

dbSNP variants (sampled 300 via entrez): RS1001654208 (6:32177850 G>A,C), RS1001880223 (6:32177658 T>G), RS1003326616 (6:32179667 C>T), RS1004356243 (6:32179380 GCTAA>G), RS1006818418 (6:32176931 A>G,T), RS1007982265 (6:32180613 G>A,T), RS1008034513 (6:32180867 G>A), RS1008194132 (6:32178236 T>A), RS1008499809 (6:32178811 A>T), RS1011877597 (6:32180921 G>T), RS1012180166 (6:32178200 G>A), RS1013351779 (6:32177420 G>A), RS1013558914 (6:32179485 G>A), RS1013612810 (6:32179868 C>T), RS1013694164 (6:32177792 G>A)

Disease associations

OMIM: gene MIM:602677 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000984_16	Idiopathic membranous nephropathy	2.000000e-40
GCST001942_21	Prostate cancer	5.000000e-09
GCST002977_1	Soluble receptor for advanced glycation end-product levels	2.000000e-08
GCST002977_2	Soluble receptor for advanced glycation end-product levels	3.000000e-16
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_10	Autism spectrum disorder or schizophrenia	2.000000e-13
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_226	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_276	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST004862_238	Itch intensity from mosquito bite adjusted by bite size	2.000000e-07
GCST008916_27	Asthma	5.000000e-31
GCST009108_5	Waist circumference variance	7.000000e-12
GCST009122_6	Waist circumference	6.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007622	sRAGE measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465346 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
4-oxoretinoic acid	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Alitretinoin	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Progesterone	increases expression	1
Silicon Dioxide	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	increases expression	1
Zinc	increases expression	1
Isotretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	affects expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5351136	Binding	Binding affinity to recombinant human RNF5 (1 to 117 residues) expressed in Escherichia coli BL21(DE3) at 50 uM by Microscale thermophoresis analysis	Innovative Strategy toward Mutant CFTR Rescue in Cystic Fibrosis: Design and Synthesis of Thiadiazole Inhibitors of the E3 Ligase RNF5. — J Med Chem

Clinical trials (associated diseases)

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