RNF26

Summary

RNF26 (ring finger protein 26, HGNC:14646) is a protein-coding gene on chromosome 11q23.3, encoding E3 ubiquitin-protein ligase RNF26 (Q9BY78). E3 ubiquitin-protein ligase that plays a key role in endosome organization by retaining vesicles in the perinuclear cloud.

The protein encoded by this intronless gene contains a C3HC5 type of RING finger, a motif known to be involved in protein-DNA and protein-protein interactions. The expression of this gene was found to be upregulated in cancer cell lines derived from different types of cancer.

Source: NCBI Gene 79102 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_032015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14646
Approved symbol	RNF26
Name	ring finger protein 26
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC2642
Ensembl gene	ENSG00000173456
Ensembl biotype	protein_coding
OMIM	606130
Entrez	79102

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000311413

RefSeq mRNA: 1 — MANE Select: NM_032015 NM_032015

CCDS: CCDS8419

Canonical transcript exons

ENST00000311413 — 1 exons

Exon	Start	End
ENSE00001206659	119334527	119337309

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 91.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.5433 / max 301.5538, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117112	72.5433	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	91.82	gold quality
ventricular zone	UBERON:0003053	89.75	gold quality
stromal cell of endometrium	CL:0002255	89.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.48	gold quality
lower esophagus	UBERON:0013473	88.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.95	gold quality
mucosa of transverse colon	UBERON:0004991	86.89	gold quality
smooth muscle tissue	UBERON:0001135	86.85	gold quality
esophagus	UBERON:0001043	86.62	gold quality
prefrontal cortex	UBERON:0000451	86.25	gold quality
right coronary artery	UBERON:0001625	86.23	gold quality
popliteal artery	UBERON:0002250	86.11	gold quality
tibial artery	UBERON:0007610	86.11	gold quality
body of stomach	UBERON:0001161	86.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.96	gold quality
aorta	UBERON:0000947	85.95	gold quality
thoracic aorta	UBERON:0001515	85.87	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.79	gold quality
descending thoracic aorta	UBERON:0002345	85.76	gold quality
ascending aorta	UBERON:0001496	85.72	gold quality
mucosa of stomach	UBERON:0001199	85.63	gold quality
apex of heart	UBERON:0002098	85.63	gold quality
kidney epithelium	UBERON:0004819	85.63	silver quality
body of uterus	UBERON:0009853	85.60	gold quality
ganglionic eminence	UBERON:0004023	85.42	gold quality
esophagus mucosa	UBERON:0002469	85.34	gold quality
nipple	UBERON:0002030	85.26	gold quality
left uterine tube	UBERON:0001303	85.24	gold quality
transverse colon	UBERON:0001157	84.73	gold quality
right adrenal gland	UBERON:0001233	84.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

60 targeting RNF26, 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-6825-5P	99.96	69.81	3431
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-626	98.89	66.21	762
HSA-MIR-6776-5P	98.54	67.43	1304

Literature-anchored findings (GeneRIF, showing 1)

• Study reveals the endoplasmic reticulum (ER)-located ubiquitin ligase Ring finger protein 26 (RNF26) as the global architect of the entire endosomal system, including the trans-Golgi network. (PMID:27368102)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf26	ENSDARG00000074074
mus_musculus	Rnf26	ENSMUSG00000053128
mus_musculus	Rnf26rt	ENSMUSG00000072476
mus_musculus	Gm49380	ENSMUSG00000111409
rattus_norvegicus	Rnf26	ENSRNOG00000007720
caenorhabditis_elegans		WBGENE00008343

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF26 — Q9BY78 (reviewed: Q9BY78)

Alternative names: RING finger protein 26

All UniProt accessions (1): Q9BY78

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that plays a key role in endosome organization by retaining vesicles in the perinuclear cloud. Acts as a platform for perinuclear positioning of the endosomal system by mediating ubiquitination of SQSTM1 through interaction with the ubiquitin conjugating enzyme UBE2J1. Ubiquitinated SQSTM1 attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport. Also acts as a regulator of type I interferon production in response to viral infection by mediating the formation of ‘Lys-11’-linked polyubiquitin chains on TMEM173/STING, leading to stabilize TMEM173/STING. Also required to limit type I interferon response by promoting autophagic degradation of IRF3.

Subunit / interactions. Interacts with INCA1. Interacts with TMEM43, ENDOD1, TMEM33 and TMED1 to form a complex capable of modulating innate immune signaling through the cGAS-STING pathway. Interacts with UBE2J1; this interaction is important for SQSTM1 ubiquitination.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous. Up-regulated in several cancer cell lines.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_114404* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR040089	RNF26_mRING-HC-C3HC5	Domain

Pfam: PF13920

UniProt features (12 total): transmembrane region 5, mutagenesis site 5, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY78-F1	74.84	0.09

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 (5):

Position	Phenotype
401	strongly decreased e3 ubiquitin-protein ligase activity. impaired ability to mediate ubiquitination of tmem173/sting.
432	about 4-fold increase of stability (from 30 min to 2 hours).
382	strongly decreased e3 ubiquitin-protein ligase activity due to impaired interaction with e2 enzymes. impaired ability to
395	strongly decreased e3 ubiquitin-protein ligase activity. impaired ability to mediate ubiquitination of tmem173/sting.
399	strongly decreased e3 ubiquitin-protein ligase activity. impaired ability to mediate ubiquitination of tmem173/sting.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 145 (showing top): GOBP_ENDOSOME_ORGANIZATION, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GGGNRMNNYCAT_UNKNOWN, GOBP_VESICLE_ORGANIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, CTATGCA_MIR153, YY1_Q6, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_PROTEIN_K11_LINKED_UBIQUITINATION, YY1_02

GO Biological Process (7): ubiquitin-dependent protein catabolic process (GO:0006511), endosome organization (GO:0007032), protein ubiquitination (GO:0016567), regulation of type I interferon production (GO:0032479), negative regulation of defense response to virus (GO:0050687), protein K11-linked ubiquitination (GO:0070979), protein localization to perinuclear region of cytoplasm (GO:1905719)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	1
modification-dependent protein catabolic process	1
endomembrane system organization	1
vesicle organization	1
protein modification by small protein conjugation	1
regulation of cytokine production	1
type I interferon production	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of defense response to virus	1
defense response to virus	1
protein polyubiquitination	1
intracellular protein localization	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1012 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF26	RNF5	Q99942	708
RNF26	TMEM33	P57088	677
RNF26	ENDOD1	O94919	658
RNF26	TRIM56	Q9BRZ2	655
RNF26	USP15	Q9Y4E8	645
RNF26	TRIM32	Q13049	607
RNF26	TMEM43	Q9BTV4	601
RNF26	TOLLIP	Q9H0E2	574
RNF26	RNF185	Q96GF1	571
RNF26	AMFR	P26442	548
RNF26	NLRC3	Q7RTR2	539
RNF26	TRIM29	Q14134	503
RNF26	ZDHHC1	Q8WTX9	493
RNF26	TRIM26	Q12899	477
RNF26	PPM1A	P35813	462

IntAct

35 interactions, top by confidence:

A	B	Type	Score
RNF26	TSC1	psi-mi:“MI:0915”(physical association)	0.620
TSC1	RNF26	psi-mi:“MI:0915”(physical association)	0.620
TSC1	RNF26	psi-mi:“MI:0403”(colocalization)	0.620
RNF26	TSC1	psi-mi:“MI:2364”(proximity)	0.620
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
RNF26	UBE2D2	psi-mi:“MI:0915”(physical association)	0.550
RNF26	UBE2D3	psi-mi:“MI:0915”(physical association)	0.550
RNF26	UBE2W	psi-mi:“MI:0915”(physical association)	0.550
UBE2D2	RNF26	psi-mi:“MI:0915”(physical association)	0.550
UBE2D3	RNF26	psi-mi:“MI:0915”(physical association)	0.550
UBE2W	RNF26	psi-mi:“MI:0915”(physical association)	0.550
RNF26	NME2P1	psi-mi:“MI:0914”(association)	0.530
INCA1	RNF26	psi-mi:“MI:0915”(physical association)	0.510
RNF26	CDK4	psi-mi:“MI:0915”(physical association)	0.400
CDK4	RNF26	psi-mi:“MI:0915”(physical association)	0.400
UBE2G2	RNF26	psi-mi:“MI:0915”(physical association)	0.370
UBE2Q1	RNF26	psi-mi:“MI:0915”(physical association)	0.370
UBE2U	RNF26	psi-mi:“MI:0915”(physical association)	0.370
RNF26	UBE2D1	psi-mi:“MI:0915”(physical association)	0.370
UBE2E1	RNF26	psi-mi:“MI:0915”(physical association)	0.370
RNF26	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
LDAF1	SLC19A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (157): RNF26 (Two-hybrid), RNF26 (Two-hybrid), RNF26 (Two-hybrid), RNF26 (Two-hybrid), RNF26 (Two-hybrid), RNF26 (Two-hybrid), ZNF143 (Affinity Capture-MS), RBM26 (Affinity Capture-MS), PSME1 (Affinity Capture-MS), CUEDC2 (Affinity Capture-MS), CYB5R3 (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), STOM (Affinity Capture-MS), RAB1B (Affinity Capture-MS)

ESM2 similar proteins: A0A2Y9GDB5, A2RUW7, A6NJJ6, A8MXV6, D2H5P6, D4A8G9, E1BLZ4, E1C7U0, O95873, P0DKW1, P0DML4, P0DML5, P0DML6, P0DMN8, P0DOC4, P0DP53, P0DTG9, P0DTH0, P0DTH1, P0DTH2, P0DTH3, P0DTH4, P0DUP6, P24001, P55056, P55057, P55797, Q2TBQ4, Q3SYR5, Q5EAA5, Q5M844, Q5R7E2, Q61268, Q6MG51, Q6P0A1, Q6UE05, Q6UJB9, Q6ZR85, Q7TSF4, Q8BUH7

Diamond homologs: A1E2V0, A1L020, A1L3F4, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, E3SCZ8, O08863, O10296, O10324, O14064, O15392, O62640, O70201, O88738, P40629, P41435, P41436, P41437, P41454, P47732, P98170, Q05AK5, Q0WPJ7, Q13489, Q13490, Q28ER3, Q28H51, Q50L39, Q557E7, Q5BKL8, Q5R881, Q5RAH9, Q60989, Q62210, Q69Z36, Q6I6F4, Q6J1J1, Q6NTT6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RNF26	“up-regulates activity”	SQSTM1	ubiquitination
Ub:E2	“up-regulates activity”	RNF26	ubiquitination
RNF26	“up-regulates activity”	STING1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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	5	96.9×	7e-08
Antigen processing: Ubiquitination & Proteasome degradation	9	17.6×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	6	48.1×	1e-07
protein polyubiquitination	8	44.0×	7e-10
ubiquitin-dependent protein catabolic process	6	21.2×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

12 predictions. Top by Δscore:

Variant	Effect	Δscore
11:119334610:TGCA:T	donor_gain	0.7200
11:119334629:G:GT	donor_gain	0.5500
11:119334552:G:GG	donor_gain	0.5100
11:119334629:G:T	donor_gain	0.5100
11:119334551:A:AG	donor_gain	0.5000
11:119334547:GCGGA:G	donor_gain	0.4700
11:119334611:GCAA:G	donor_gain	0.4500
11:119334549:G:GT	donor_gain	0.4100
11:119334825:C:G	donor_gain	0.3000
11:119334556:GGGC:G	donor_gain	0.2400
11:119334557:G:T	donor_gain	0.2300
11:119334550:GA:G	donor_gain	0.2000

AlphaMissense

2739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:119336260:T:A	C380S	1.000
11:119336260:T:C	C380R	1.000
11:119336261:G:C	C380S	1.000
11:119336261:G:A	C380Y	0.999
11:119336262:T:G	C380W	0.999
11:119336267:T:A	I382N	0.999
11:119336269:T:A	C383S	0.999
11:119336269:T:C	C383R	0.999
11:119336270:G:A	C383Y	0.999
11:119336270:G:C	C383S	0.999
11:119336271:C:G	C383W	0.999
11:119336286:G:C	K388N	0.999
11:119336286:G:T	K388N	0.999
11:119336305:T:C	C395R	0.999
11:119336311:C:G	H397D	0.999
11:119336313:T:A	H397Q	0.999
11:119336313:T:G	H397Q	0.999
11:119336323:T:C	C401R	0.999
11:119336332:T:C	C404R	0.999
11:119336333:G:A	C404Y	0.999
11:119336334:C:G	C404W	0.999
11:119336374:T:C	C418R	0.999
11:119336376:C:G	C418W	0.999
11:119336383:T:A	C421S	0.999
11:119336383:T:C	C421R	0.999
11:119336384:G:C	C421S	0.999
11:119336261:G:T	C380F	0.998
11:119336267:T:C	I382T	0.998
11:119336267:T:G	I382S	0.998
11:119336270:G:T	C383F	0.998

dbSNP variants (sampled 300 via entrez): RS1000151481 (11:119335003 G>A), RS1000274665 (11:119334651 C>T), RS1000889657 (11:119333296 C>T), RS1000899962 (11:119337352 AG>A), RS1001489294 (11:119333647 T>A), RS1002046451 (11:119333726 C>T), RS1002068285 (11:119337598 T>C), RS1002670240 (11:119336605 C>T), RS1002734505 (11:119334124 A>C), RS1003409651 (11:119336885 G>C), RS1003468923 (11:119333644 G>A), RS1004067154 (11:119334412 G>C,T), RS1004122297 (11:119335155 G>A), RS1004313631 (11:119335713 C>T), RS1005074469 (11:119332875 C>T)

Disease associations

OMIM: gene MIM:606130 | 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
GCST010002_199	Refractive error	3.000000e-34
GCST90002402_396	Platelet count	5.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Resveratrol	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	increases reaction, affects binding	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Aspirin	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Plant Oils	decreases expression	1

Clinical trials (associated diseases)

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