RNF208

Summary

RNF208 (ring finger protein 208, HGNC:25420) is a protein-coding gene on chromosome 9q34.3, encoding RING finger protein 208 (Q9H0X6).

Enables ubiquitin-protein transferase activity. Involved in protein autoubiquitination. Located in cytosol and nucleoplasm.

Source: NCBI Gene 727800 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_031297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25420
Approved symbol	RNF208
Name	ring finger protein 208
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP761H1710
Ensembl gene	ENSG00000212864
Ensembl biotype	protein_coding
OMIM	618993
Entrez	727800

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000391553, ENST00000392827, ENST00000905461, ENST00000905462, ENST00000905463, ENST00000905464

RefSeq mRNA: 3 — MANE Select: NM_031297 NM_001388297, NM_001388298, NM_031297

CCDS: CCDS7037

Canonical transcript exons

ENST00000391553 — 2 exons

Exon	Start	End
ENSE00001509333	137220259	137221738
ENSE00003925496	137221989	137222240

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 97.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1234 / max 7.6096, expressed in 53 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103332	0.1234	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	97.40	gold quality
anterior cingulate cortex	UBERON:0009835	96.66	gold quality
cingulate cortex	UBERON:0003027	96.58	gold quality
lower esophagus mucosa	UBERON:0035834	95.78	gold quality
apex of heart	UBERON:0002098	94.72	gold quality
amygdala	UBERON:0001876	94.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.75	gold quality
prefrontal cortex	UBERON:0000451	93.73	gold quality
nucleus accumbens	UBERON:0001882	92.46	gold quality
cerebellar hemisphere	UBERON:0002245	92.36	gold quality
cerebellar cortex	UBERON:0002129	92.24	gold quality
caudate nucleus	UBERON:0001873	92.20	gold quality
putamen	UBERON:0001874	91.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.42	gold quality
neocortex	UBERON:0001950	91.38	gold quality
frontal cortex	UBERON:0001870	91.21	gold quality
hypothalamus	UBERON:0001898	90.07	gold quality
heart left ventricle	UBERON:0002084	89.56	gold quality
cerebellum	UBERON:0002037	89.42	gold quality
cerebral cortex	UBERON:0000956	88.73	gold quality
cardiac ventricle	UBERON:0002082	88.67	gold quality
telencephalon	UBERON:0001893	88.56	gold quality
right atrium auricular region	UBERON:0006631	88.15	gold quality
forebrain	UBERON:0001890	87.85	gold quality
right adrenal gland cortex	UBERON:0035827	87.70	gold quality
right adrenal gland	UBERON:0001233	87.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.48	gold quality
Ammon’s horn	UBERON:0001954	87.24	gold quality
brain	UBERON:0000955	87.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	9.05
E-ANND-3	no	2.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESRRA

miRNA regulators (miRDB)

22 targeting RNF208, 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-3185	99.99	68.12	1959
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-647	97.73	67.79	927
HSA-MIR-4715-5P	97.62	67.47	506
HSA-MIR-6781-5P	94.61	59.49	155

Literature-anchored findings (GeneRIF, showing 1)

• RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of triple-negative breast cancer (TNBC) cells. RNF208 was significantly lower in TNBC than the luminal type, and low expression of RNF208 was strongly associated with poor clinical outcomes. (PMID:31862882)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	RNF208	ENSDARG00000078056
mus_musculus	Rnf208	ENSMUSG00000044628
rattus_norvegicus	Rnf208	ENSRNOG00000010607

Paralogs (3): RNF183 (ENSG00000165188), RNF223 (ENSG00000237330), RNF225 (ENSG00000269855)

Protein

Protein identifiers

RING finger protein 208 — Q9H0X6 (reviewed: Q9H0X6)

All UniProt accessions (1): Q9H0X6

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (3): NP_001375226, NP_001375227, NP_112587* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR040100	RNF208_RING-HC	Domain
IPR051435	RING_finger_E3_ubiq-ligases	Family

UniProt features (4 total): chain 1, zinc finger region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0X6-F1	62.35	0.05

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 (1): 102

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_PROTEIN_AUTOUBIQUITINATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, MEISSNER_ES_ICP_WITH_H3K4ME3, MEISSNER_BRAIN_ICP_WITH_H3K4ME3, MIKKELSEN_ES_ICP_WITH_H3K4ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, chr9q34, HMG20B_TARGET_GENES, MIR182_5P, MIR4470, MIR92A_2_5P

GO Biological Process (2): protein ubiquitination (GO:0016567), protein autoubiquitination (GO:0051865)

GO Molecular Function (5): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein modification by small protein conjugation	1
protein ubiquitination	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF208	STPG1	Q5TH74	642
RNF208	ZNF497	Q6ZNH5	570
RNF208	HMCES	Q96FZ2	541
RNF208	SMTNL1	A8MU46	520
RNF208	TCTN1	Q2MV58	519
RNF208	POMGNT2	Q8NAT1	510
RNF208	SLC44A3	Q8N4M1	506
RNF208	OR4F21	O95013	479
RNF208	ZNF487	B1APH4	475
RNF208	ENTREP1	Q15884	447
RNF208	GARIN5A	Q6IPT2	447
RNF208	RNF141	Q8WVD5	429
RNF208	ZNF575	Q86XF7	427
RNF208	SERTAD3	Q9UJW9	421
RNF208	CA12	O43570	420

IntAct

94 interactions, top by confidence:

A	B	Type	Score
DAZAP2	RNF208	psi-mi:“MI:0915”(physical association)	0.780
RNF208	DAZAP2	psi-mi:“MI:0915”(physical association)	0.780
RNF208	RPIA	psi-mi:“MI:0915”(physical association)	0.560
RNF208	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
RPIA	RNF208	psi-mi:“MI:0915”(physical association)	0.560
RNF38	RNF208	psi-mi:“MI:0915”(physical association)	0.560
PIN1	RNF208	psi-mi:“MI:0915”(physical association)	0.560
	RNF208	psi-mi:“MI:0915”(physical association)	0.560
RNF208	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
USP54	RNF208	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	RNF208	psi-mi:“MI:0915”(physical association)	0.560
OXER1	RNF208	psi-mi:“MI:0915”(physical association)	0.560
KRTAP26-1	RNF208	psi-mi:“MI:0915”(physical association)	0.560
KRTAP15-1	RNF208	psi-mi:“MI:0915”(physical association)	0.560
CREB5	RNF208	psi-mi:“MI:0915”(physical association)	0.560
GRB2	RNF208	psi-mi:“MI:0915”(physical association)	0.560
STAC	RNF208	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (76): RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid), RNF208 (Two-hybrid)

ESM2 similar proteins: A0A140LI67, A6NCQ9, D2H6Z0, D4A039, D4A723, E1C2W7, O43187, P59729, Q0P5I2, Q29RU0, Q3SWY0, Q3T0Y9, Q3U2C5, Q4QQS0, Q58EC8, Q5PQS0, Q5R810, Q5RF74, Q5XIS1, Q68DX3, Q68EV7, Q6GND7, Q6INB3, Q6IRN0, Q7TSI1, Q80TQ5, Q8BG47, Q8BW88, Q8C008, Q8IWE5, Q8K0W3, Q8K330, Q8N8N0, Q8NC42, Q8QHJ9, Q8QZS5, Q8TB24, Q8TEB7, Q8TF17, Q8WYP3

Diamond homologs: A0A7I2V3R4, A6NIN4, D2H788, D3ZBM4, O70277, O75382, Q13049, Q3T0Y9, Q6IMG5, Q6INB3, Q8C432, Q8CH72, Q8K0W3, Q8N6D2, Q9DCB3, Q9FY48, Q9H0X6, Q9NXI6, Q9R1R2, A5D8S5, D2H6Z0, D4A723, E1C2W7, E7ERA6, M0QZC1, Q3SWY0, Q3UV31, Q58EC8, Q5RBR0, Q68EV7, Q69ZI1, Q71F54, Q7Z6J0, Q8BG47, Q8IWR1, Q8N8N0, Q8QZS5, Q96D59, Q9D241, Q9D7D1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RNF208	“down-regulates quantity by destabilization”	VIM	ubiquitination
ESRRA	“up-regulates quantity by expression”	RNF208	“transcriptional regulation”
Ub:E2	“up-regulates activity”	RNF208	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

86 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137221127:T:TG	acceptor_gain	0.4900
9:137220852:A:AC	donor_gain	0.4500
9:137220853:C:CC	donor_gain	0.4500
9:137220830:G:T	acceptor_gain	0.4400
9:137221503:T:TA	donor_gain	0.4400
9:137220727:G:GT	acceptor_gain	0.4300
9:137220705:ACTGC:A	acceptor_gain	0.4100
9:137221128:T:A	acceptor_gain	0.3900
9:137221436:G:T	acceptor_gain	0.3900
9:137221507:AC:A	donor_gain	0.3900
9:137221508:CC:C	donor_gain	0.3900
9:137220708:G:A	donor_gain	0.3700
9:137220820:C:CT	acceptor_gain	0.3700
9:137220911:C:A	donor_gain	0.3700
9:137221499:AGGGT:A	donor_gain	0.3700
9:137221446:G:GT	acceptor_gain	0.3600
9:137221127:T:C	acceptor_gain	0.3500
9:137220706:CTGCT:C	acceptor_gain	0.3400
9:137220761:T:TC	acceptor_gain	0.3400
9:137221126:CT:C	acceptor_gain	0.3200
9:137221506:C:T	donor_gain	0.3200
9:137220713:CACA:C	donor_gain	0.3100
9:137221410:T:TA	acceptor_gain	0.3100
9:137221477:C:A	donor_gain	0.3100
9:137221502:GTCT:G	donor_loss	0.3100
9:137221503:TCTCA:T	donor_loss	0.3100
9:137221504:CT:C	donor_loss	0.3100
9:137221505:TCA:T	donor_loss	0.3100
9:137221506:CA:C	donor_loss	0.3100
9:137221507:A:C	donor_loss	0.3100

AlphaMissense

1661 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137220625:G:C	F196L	1.000
9:137220625:G:T	F196L	1.000
9:137220626:A:G	F196S	1.000
9:137220627:A:G	F196L	1.000
9:137220629:A:T	L195H	1.000
9:137220646:G:C	C189W	1.000
9:137220647:C:A	C189F	1.000
9:137220647:C:G	C189S	1.000
9:137220647:C:T	C189Y	1.000
9:137220648:A:G	C189R	1.000
9:137220648:A:T	C189S	1.000
9:137220655:G:C	C186W	1.000
9:137220656:C:G	C186S	1.000
9:137220656:C:T	C186Y	1.000
9:137220657:A:C	C186G	1.000
9:137220657:A:G	C186R	1.000
9:137220657:A:T	C186S	1.000
9:137220662:A:T	I184N	1.000
9:137220664:G:C	F183L	1.000
9:137220664:G:T	F183L	1.000
9:137220665:A:G	F183S	1.000
9:137220666:A:G	F183L	1.000
9:137220701:A:G	L171P	1.000
9:137220703:G:C	C170W	1.000
9:137220704:C:G	C170S	1.000
9:137220705:A:G	C170R	1.000
9:137220705:A:T	C170S	1.000
9:137220712:A:C	C167W	1.000
9:137220713:C:G	C167S	1.000
9:137220713:C:T	C167Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000364277 (9:137224936 T>A), RS1000707195 (9:137223492 C>G,T), RS1000770746 (9:137223767 G>A,C), RS1000987831 (9:137223515 C>G), RS1001341160 (9:137220823 C>G,T), RS1001551269 (9:137220033 C>T), RS1002217239 (9:137224173 C>A,T), RS1002346914 (9:137222719 G>A), RS1002441843 (9:137222922 C>T), RS1003213445 (9:137225251 G>A,C), RS1003267581 (9:137225071 G>A,C,T), RS1003868546 (9:137225324 T>C,G), RS1004228476 (9:137222189 G>A), RS1004899885 (9:137222037 C>T), RS1005514035 (9:137224166 G>A,C)

Disease associations

OMIM: gene MIM:618993 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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