RNFT2

Summary

RNFT2 (ring finger protein, transmembrane 2, HGNC:25905) is a protein-coding gene on chromosome 12q24.22, encoding E3 ubiquitin-protein ligase RNFT2 (Q96EX2). E3 ubiquitin-protein ligase that negatively regulates IL3-dependent cellular responses through IL3RA ubiquitination and degradation by the proteasome, having an anti-inflammatory effect.

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in positive regulation of ERAD pathway. Predicted to be located in membrane.

Source: NCBI Gene 84900 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_001382266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25905
Approved symbol	RNFT2
Name	ring finger protein, transmembrane 2
Location	12q24.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14627
Ensembl gene	ENSG00000135119
Ensembl biotype	protein_coding
OMIM	620254
Entrez	84900

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000257575, ENST00000392549, ENST00000407967, ENST00000547718, ENST00000551251, ENST00000552920, ENST00000615278, ENST00000677328

RefSeq mRNA: 3 — MANE Select: NM_001382266 NM_001109903, NM_001382266, NM_032814

CCDS: CCDS44987, CCDS9180

Canonical transcript exons

ENST00000257575 — 11 exons

Exon	Start	End
ENSE00001630304	116849314	116853631
ENSE00002214965	116741036	116741094
ENSE00002301602	116740345	116740521
ENSE00002403688	116738315	116738370
ENSE00003487036	116766814	116766914
ENSE00003596702	116833792	116833941
ENSE00003608125	116753984	116754060
ENSE00003616202	116749841	116750307
ENSE00003633550	116779195	116779348
ENSE00003674060	116836181	116836282
ENSE00003688416	116835960	116836025

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 94.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9176 / max 185.4348, expressed in 1200 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128242	4.8497	985
128241	0.9751	483
128244	0.5765	228
128243	0.5163	282

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.71	gold quality
middle temporal gyrus	UBERON:0002771	94.70	gold quality
endothelial cell	CL:0000115	93.68	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.58	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.67	gold quality
primary visual cortex	UBERON:0002436	88.57	gold quality
CA1 field of hippocampus	UBERON:0003881	87.88	gold quality
superior frontal gyrus	UBERON:0002661	87.69	gold quality
postcentral gyrus	UBERON:0002581	87.19	gold quality
sperm	CL:0000019	86.90	gold quality
pons	UBERON:0000988	86.83	gold quality
orbitofrontal cortex	UBERON:0004167	86.75	gold quality
right frontal lobe	UBERON:0002810	86.70	gold quality
entorhinal cortex	UBERON:0002728	86.48	gold quality
occipital lobe	UBERON:0002021	86.35	gold quality
parietal lobe	UBERON:0001872	86.33	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.10	gold quality
prefrontal cortex	UBERON:0000451	86.03	gold quality
frontal cortex	UBERON:0001870	85.95	gold quality
male germ cell	CL:0000015	85.75	gold quality
neocortex	UBERON:0001950	85.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.62	gold quality
substantia nigra pars compacta	UBERON:0001965	85.56	gold quality
cerebral cortex	UBERON:0000956	85.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.53	gold quality
cerebellar vermis	UBERON:0004720	85.43	gold quality
telencephalon	UBERON:0001893	84.68	gold quality
putamen	UBERON:0001874	84.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.39	gold quality
hypothalamus	UBERON:0001898	84.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting RNFT2, 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-4531	99.99	69.70	3181
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-6072	98.00	66.47	804

Literature-anchored findings (GeneRIF, showing 2)

• The RNFT2/IL-3Ralpha axis regulates IL-3 signaling and innate immunity. (PMID:31990690)
• Tissue RNFT2 Expression Levels Are Associated With Peritoneal Recurrence and Poor Prognosis in Gastric Cancer. (PMID:33517265)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnft2	ENSDARG00000053019
mus_musculus	Rnft2	ENSMUSG00000032850
rattus_norvegicus	Rnft2	ENSRNOG00000001124
drosophila_melanogaster	CG13605	FBGN0039150
caenorhabditis_elegans		WBGENE00022502

Paralogs (1): RNFT1 (ENSG00000189050)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNFT2 — Q96EX2 (reviewed: Q96EX2)

Alternative names: RING finger and transmembrane domain-containing protein 2, Transmembrane protein 118

All UniProt accessions (3): A0A7I2V5U1, Q96EX2, F8VZS7

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that negatively regulates IL3-dependent cellular responses through IL3RA ubiquitination and degradation by the proteasome, having an anti-inflammatory effect.

Subcellular location. Membrane.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96EX2-1	1	yes
Q96EX2-2	2
Q96EX2-3	3
Q96EX2-4	4
Q96EX2-5	5

RefSeq proteins (3): NP_001103373, NP_001369195, NP_116203 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR044235	RNFT1/2	Family

Pfam: PF13639

UniProt features (24 total): splice variant 6, topological domain 5, transmembrane region 4, mutagenesis site 3, region of interest 2, compositionally biased region 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EX2-F1	70.89	0.28

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
387	loss of e3 ubiquitin-protein ligase activity.
401	loss of e3 ubiquitin-protein ligase activity.
418	loss of e3 ubiquitin-protein ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_451, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, MCAATNNNNNGCG_UNKNOWN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, ONDER_CDH1_TARGETS_2_UP, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS

GO Biological Process (1): positive regulation of ERAD pathway (GO:1904294)

GO Molecular Function (3): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), metal ion binding (GO:0046872)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ERAD pathway	1
positive regulation of proteasomal protein catabolic process	1
regulation of ERAD pathway	1
positive regulation of response to endoplasmic reticulum stress	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNFT2	RNF223	E7ERA6	568
RNFT2	Q6NXN5	Q6NXN5	544
RNFT2	RNF183	Q96D59	467
RNFT2	TMEM129	A0AVI4	449
RNFT2	RNF130	Q86XS8	440
RNFT2	DZANK1	Q9NVP4	432
RNFT2	RNF144A	P50876	431
RNFT2	GPRIN1	Q7Z2K8	430
RNFT2	SIRAL2	Q9NWS6	422
RNFT2	PRR18	Q8N4B5	422
RNFT2	RAPGEFL1	Q9UHV5	421
RNFT2	RSPRY1	Q96DX4	417
RNFT2	CGRRF1	Q99675	413
RNFT2	CPNE9	Q8IYJ1	398
RNFT2	LAPTM4A	Q15012	393

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ESR2	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): RNFT2 (PCA), RNFT2 (Proximity Label-MS), RNFT2 (Affinity Capture-RNA), RNFT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8FG46, A0A1L8FM16, A0A1L8FZ98, A0A1L8H814, A1L3G9, A8X0L4, B0JYZ2, B1AUE5, B9X187, C0HKD7, E7F4V8, E7FE40, F1QB30, F1S5L4, O88177, P24392, P28328, P32800, P55098, P97564, Q00940, Q05568, Q059Y8, Q06438, Q19189, Q19337, Q28EH9, Q3U213, Q3UF64, Q5GJ77, Q5RAG4, Q5SNQ7, Q5Z880, Q61586, Q642F4, Q68F70, Q6DFK1, Q6INN0, Q6NPT7, Q6NZ21

Diamond homologs: A0A1L8FG46, A0A1L8FM16, B1AUE5, C0HBT3, C0HKD7, D2H0Y8, E1B7X3, O60683, O64425, P22681, P22682, P87176, P93030, Q09463, Q13191, Q1ACD5, Q28GL3, Q2PFU6, Q3T139, Q3TTA7, Q3UF64, Q587N7, Q5C8U1, Q5C8U3, Q5C8U4, Q5D7H8, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7J2, Q5M7Z0, Q5REL3, Q5XIK5, Q66JE4, Q680I0, Q6DFR2, Q6GQD5, Q6GQL0, Q6NRE7, Q6NTV1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNFT2	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2418 predictions. Top by Δscore:

Variant	Effect	Δscore
12:116753978:CCACA:C	acceptor_loss	1.0000
12:116753979:CACAG:C	acceptor_loss	1.0000
12:116753981:CAGG:C	acceptor_loss	1.0000
12:116753982:A:AG	acceptor_gain	1.0000
12:116753982:A:C	acceptor_loss	1.0000
12:116753983:G:GA	acceptor_gain	1.0000
12:116753983:GGC:G	acceptor_gain	1.0000
12:116754061:GTG:G	donor_loss	1.0000
12:116754062:T:A	donor_loss	1.0000
12:116766812:A:AG	acceptor_gain	1.0000
12:116766813:G:GG	acceptor_gain	1.0000
12:116766915:GTGA:G	donor_loss	1.0000
12:116766916:T:A	donor_loss	1.0000
12:116779190:CCCA:C	acceptor_loss	1.0000
12:116779191:CCAG:C	acceptor_loss	1.0000
12:116779192:CA:C	acceptor_loss	1.0000
12:116779193:A:AG	acceptor_gain	1.0000
12:116779194:G:GA	acceptor_gain	1.0000
12:116779194:GC:G	acceptor_gain	1.0000
12:116779194:GCC:G	acceptor_gain	1.0000
12:116779194:GCCT:G	acceptor_gain	1.0000
12:116779194:GCCTC:G	acceptor_gain	1.0000
12:116779345:CAAGG:C	donor_loss	1.0000
12:116779349:GTAGG:G	donor_loss	1.0000
12:116833781:T:TA	acceptor_gain	1.0000
12:116833783:T:TA	acceptor_gain	1.0000
12:116833784:G:A	acceptor_gain	1.0000
12:116833787:T:TA	acceptor_gain	1.0000
12:116833788:GCAG:G	acceptor_loss	1.0000
12:116833790:A:AG	acceptor_gain	1.0000

AlphaMissense

2878 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:116836232:T:A	C384S	1.000
12:116836232:T:C	C384R	1.000
12:116836233:G:A	C384Y	1.000
12:116836233:G:C	C384S	1.000
12:116836233:G:T	C384F	1.000
12:116836234:C:G	C384W	1.000
12:116836239:T:A	I386N	1.000
12:116836241:T:A	C387S	1.000
12:116836241:T:C	C387R	1.000
12:116836242:G:A	C387Y	1.000
12:116836242:G:C	C387S	1.000
12:116836242:G:T	C387F	1.000
12:116836243:T:G	C387W	1.000
12:116836277:T:C	C399R	1.000
12:116836278:G:A	C399Y	1.000
12:116836279:C:G	C399W	1.000
12:116849316:C:A	H401Q	1.000
12:116849316:C:G	H401Q	1.000
12:116849320:T:C	F403L	1.000
12:116849321:T:C	F403S	1.000
12:116849321:T:G	F403C	1.000
12:116849322:C:A	F403L	1.000
12:116849322:C:G	F403L	1.000
12:116849323:T:C	C404R	1.000
12:116849324:G:A	C404Y	1.000
12:116849324:G:T	C404F	1.000
12:116849325:T:G	C404W	1.000
12:116849332:T:A	C407S	1.000
12:116849332:T:C	C407R	1.000
12:116849333:G:C	C407S	1.000

dbSNP variants (sampled 300 via entrez): RS1000015444 (12:116810773 G>A), RS1000067131 (12:116765014 G>A), RS1000112560 (12:116792078 G>C), RS1000117920 (12:116836069 G>C), RS1000120352 (12:116817082 A>G), RS1000133916 (12:116766749 G>A), RS1000141732 (12:116743902 C>T), RS1000153766 (12:116787027 C>G,T), RS1000209942 (12:116787225 T>A), RS1000222312 (12:116742514 G>A,C), RS1000235553 (12:116823815 C>A,T), RS1000244233 (12:116738242 C>G,T), RS1000247300 (12:116747142 C>T), RS1000259254 (12:116792383 GTCC>G), RS1000304007 (12:116816789 C>T)

Disease associations

OMIM: gene MIM:620254 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001280_5	Alzheimer’s disease (age of onset)	3.000000e-06
GCST001762_419	Obesity-related traits	7.000000e-06
GCST002875_60	Diisocyanate-induced asthma	2.000000e-06
GCST006870_7	Hippocampal tail volume	2.000000e-19
GCST006871_6	Total hippocampal volume	2.000000e-35
GCST006886_1	Subiculum volume	1.000000e-17
GCST006887_1	Hippocampal subfield CA1 volume	7.000000e-28
GCST006888_3	Hippocampal subfield CA3 volume	2.000000e-15
GCST006889_2	Hippocampal subfield CA4 volume	2.000000e-24
GCST006890_1	Dentate gyrus granule cell layer volume	9.000000e-26
GCST006891_5	Dentate gyrus molecular layer volume	2.000000e-25
GCST010703_5	Brain morphology (MOSTest)	4.000000e-32

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0003940	physical activity
EFO:0006995	response to diisocyanate
EFO:0005035	hippocampal volume
EFO:0009394	hippocampal CA1 volume
EFO:0009395	hippocampal CA3 volume
EFO:0009396	hippocampal CA4 volume
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4767452	RNFT2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	5
trichostatin A	affects cotreatment, decreases expression, affects expression	4
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1
Ethanol	decreases expression, increases abundance, affects cotreatment	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	increases methylation	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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