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RNF180

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Summary

RNF180 (ring finger protein 180, HGNC:27752) is a protein-coding gene on chromosome 5q12.3, encoding E3 ubiquitin-protein ligase RNF180 (Q86T96). E3 ubiquitin-protein ligase which promotes polyubiquitination and degradation by the proteasome pathway of ZIC2.

Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Predicted to be involved in norepinephrine metabolic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and serotonin metabolic process. Predicted to act upstream of or within several processes, including adult behavior; positive regulation of protein ubiquitination; and protein polyubiquitination. Predicted to be located in endoplasmic reticulum; membrane; and nuclear envelope. Predicted to be active in endoplasmic reticulum membrane.

Source: NCBI Gene 285671 — RefSeq curated summary.

At a glance

  • GWAS associations: 3
  • Clinical variants (ClinVar): 92 total
  • MANE Select transcript: NM_001113561

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:27752
Approved symbolRNF180
Namering finger protein 180
Location5q12.3
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000164197
Ensembl biotypeprotein_coding
OMIM616015
Entrez285671

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000296615, ENST00000389100, ENST00000504296, ENST00000876162, ENST00000876163, ENST00000876164, ENST00000876165, ENST00000876166, ENST00000876167, ENST00000876168, ENST00000876169

RefSeq mRNA: 4 — MANE Select: NM_001113561 NM_001113561, NM_001323291, NM_001323292, NM_178532

CCDS: CCDS34169, CCDS47219

Canonical transcript exons

ENST00000389100 — 8 exons

ExonStartEnd
ENSE000010823546421355864214517
ENSE000010823556420080864200942
ENSE000012850096421206564212160
ENSE000015048836436961564372869
ENSE000015048846433028164330406
ENSE000015048856432518664325411
ENSE000017481756421736164217396
ENSE000020340106416584364165953

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 86.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8459 / max 116.7442, expressed in 973 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
566574.0602912
566561.0081322
566550.6680234
566530.070322
566540.039414

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
endothelial cellCL:000011586.00gold quality
cortical plateUBERON:000534384.86gold quality
popliteal arteryUBERON:000225084.05gold quality
tibial arteryUBERON:000761084.03gold quality
arteryUBERON:000163783.27gold quality
calcaneal tendonUBERON:000370181.61gold quality
ventricular zoneUBERON:000305381.51gold quality
aortaUBERON:000094781.08gold quality
caput epididymisUBERON:000435880.96gold quality
seminal vesicleUBERON:000099880.93gold quality
ganglionic eminenceUBERON:000402380.89gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047380.81gold quality
corpus epididymisUBERON:000435980.48gold quality
right coronary arteryUBERON:000162580.35gold quality
endometriumUBERON:000129579.94gold quality
cauda epididymisUBERON:000436079.73gold quality
islet of LangerhansUBERON:000000679.56gold quality
Brodmann (1909) area 23UBERON:001355479.42gold quality
left coronary arteryUBERON:000162679.41gold quality
saphenous veinUBERON:000731879.23gold quality
colonic epitheliumUBERON:000039779.04gold quality
descending thoracic aortaUBERON:000234578.92gold quality
medial globus pallidusUBERON:000247778.86gold quality
coronary arteryUBERON:000162178.76gold quality
epithelial cell of pancreasCL:000008377.84silver quality
smooth muscle tissueUBERON:000113577.49gold quality
thoracic aortaUBERON:000151577.35gold quality
ascending aortaUBERON:000149677.17gold quality
thyroid glandUBERON:000204676.94gold quality
tendonUBERON:000004376.49gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes8.04
E-MTAB-2983no265.99
E-CURD-89no30.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting RNF180, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-186-5P99.9970.833707
HSA-MIR-428299.9975.366408
HSA-MIR-570-3P99.9672.414910
HSA-MIR-651-3P99.9473.485177
HSA-MIR-10527-5P99.9172.283754
HSA-MIR-548E-5P99.8972.734486
HSA-MIR-612499.8769.783551
HSA-MIR-449599.8272.083080
HSA-MIR-313399.8170.923506
HSA-MIR-129999.7771.242389
HSA-MIR-875-3P99.6369.472548
HSA-MIR-425199.4069.193363
HSA-MIR-6507-5P99.3670.462524
HSA-MIR-19A-5P99.3666.931675
HSA-MIR-6744-3P99.2264.41972
HSA-MIR-4757-5P99.1264.51981
HSA-MIR-474499.0169.911581
HSA-MIR-4690-3P97.0264.72981
HSA-MIR-568597.0264.341004

Literature-anchored findings (GeneRIF, showing 10)

  • RNF180 is a novel potential tumor suppressor in gastric carcinogenesis. (PMID:21717426)
  • Data indicate that the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families. (PMID:22563461)
  • We found that only few methylated CpG sites of RNF180 promoter was appropriate to predict the survival of gastric cancer (PMID:24833402)
  • hypermethylated CpG site count of E3 ubiquitin ligase Ring finger protein 180 promoter for evaluating the prognosis of gastric cancer was reasonable by using the direct bisulfite sequencing. (PMID:25769451)
  • RNF180 is capable of inhibiting lymph node metastasis of gastric cancer by suppressing the intracellular activation of malignant molecular signals. (PMID:26805552)
  • relationships between RNF180 promoter methylation and gastric cancer or atrophic gastritis, and the effects of Helicobactor pylori (H.pylori) infection on RNF180 promoter methylation (PMID:27050149)
  • The methylated status of the key CpG islands of RNF180 DNA promoter may be used to predict the variations of the malignant biological characteristics of gastric cancer cells. (PMID:27223257)
  • RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells. (PMID:33082325)
  • DNMT3A-mediated silence in ADAMTS9 expression is restored by RNF180 to inhibit viability and motility in gastric cancer cells. (PMID:33931579)
  • E3 ubiquitin ligase RNF180 prevents excessive PCDH10 methylation to suppress the proliferation and metastasis of gastric cancer cells by promoting ubiquitination of DNMT1. (PMID:37147733)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriornf180aENSDARG00000073720
mus_musculusRnf180ENSMUSG00000021720
rattus_norvegicusRnf180ENSRNOG00000043329

Paralogs (4): RNF125 (ENSG00000101695), RNF114 (ENSG00000124226), RNF138 (ENSG00000134758), RNF166 (ENSG00000158717)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF180 — Q86T96 (reviewed: Q86T96)

Alternative names: RING finger protein 180, RING-type E3 ubiquitin transferase RNF180

All UniProt accessions (2): D6RE88, Q86T96

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which promotes polyubiquitination and degradation by the proteasome pathway of ZIC2.

Subunit / interactions. Interacts with ZIC2.

Subcellular location. Endoplasmic reticulum membrane. Nucleus envelope.

Domain organisation. The RING-type zinc finger domain mediates polyubiquitination of the interacting protein.

Pathway. Protein modification; protein ubiquitination.

Isoforms (3)

UniProt IDNamesCanonical?
Q86T96-11yes
Q86T96-22
Q86T96-33

RefSeq proteins (4): NP_001107033, NP_001310220, NP_001310221, NP_848627 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001841Znf_RINGDomain
IPR013083Znf_RING/FYVE/PHDHomologous_superfamily
IPR017907Znf_RING_CSConserved_site
IPR018957Znf_C3HC4_RING-typeDomain
IPR033263RNF180Family
IPR045790RNF180_CDomain

Pfam: PF00097, PF19332

UniProt features (14 total): sequence conflict 4, splice variant 3, topological domain 2, chain 1, transmembrane region 1, zinc finger region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q86T96-F157.300.14

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): 230

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_BEHAVIOR, GOBP_ADULT_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_INDOLE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEOLYSIS

GO Biological Process (7): protein polyubiquitination (GO:0000209), adult behavior (GO:0030534), positive regulation of protein ubiquitination (GO:0031398), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), norepinephrine metabolic process (GO:0042415), serotonin metabolic process (GO:0042428), protein ubiquitination (GO:0016567)

GO Molecular Function (6): zinc ion binding (GO:0008270), ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): nuclear envelope (GO:0005635), endoplasmic reticulum membrane (GO:0005789), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
protein ubiquitination2
endomembrane system2
intracellular membrane-bounded organelle2
behavior1
regulation of protein ubiquitination1
positive regulation of protein modification by small protein conjugation or removal1
regulation of proteasomal ubiquitin-dependent protein catabolic process1
proteasome-mediated ubiquitin-dependent protein catabolic process1
positive regulation of proteasomal protein catabolic process1
positive regulation of ubiquitin-dependent protein catabolic process1
catecholamine metabolic process1
phenol-containing compound metabolic process1
indole-containing compound metabolic process1
protein modification by small protein conjugation1
transition metal ion binding1
ubiquitin-like protein conjugating enzyme binding1
ubiquitin-protein transferase activity1
ubiquitin-like protein ligase activity1
binding1
catalytic activity1
cation binding1
nucleus1
organelle envelope1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
cytoplasm1
cellular anatomical structure1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RNF180OR11L1Q8NGX0593
RNF180UBE2E1P51965491
RNF180RPRMQ9NS64360
RNF180HTR1AP08908345
RNF180FMN1Q68DA7339
RNF180RPRMLQ8N4K4324
RNF180XKRXQ6PP77324
RNF180CDCA7LQ96GN5314
RNF180DAPK1P53355313
RNF180TMEM121BQ9BXQ6311
RNF180RNFT1Q5M7Z0307
RNF180TRIM31Q9BZY9305
RNF180ZNF492Q9P255302
RNF180CADM2Q8N3J6300
RNF180RNF223E7ERA6299

IntAct

4 interactions, top by confidence:

ABTypeScore
RNF180YWHAEpsi-mi:“MI:0915”(physical association)0.400
SFNRNF180psi-mi:“MI:0915”(physical association)0.400

BioGRID (33): RNF180 (Affinity Capture-MS), RNF180 (Affinity Capture-MS), PLK2 (Affinity Capture-Western), RNF180 (Affinity Capture-Western), RNF180 (Reconstituted Complex), ZIC2 (Reconstituted Complex), ZIC2 (Affinity Capture-Western), RNF180 (Affinity Capture-Western), CBX4 (Affinity Capture-Western), RNF180 (Affinity Capture-Western), RNF180 (Affinity Capture-Western), DNMT1 (Affinity Capture-Western), NOTCH1 (Affinity Capture-Western), TRIM24 (Affinity Capture-Western), FOXC1 (Affinity Capture-Western)

ESM2 similar proteins: A6H5X4, B1AUS7, D0QMC3, O35368, O60224, O60225, P0C6Y7, P0DOV1, P0DOV2, P23497, P41218, Q15361, Q16384, Q16385, Q16666, Q2KIN0, Q3U827, Q3ZCI6, Q4R7Q1, Q504N7, Q5H9L4, Q5I0E2, Q5I0J8, Q5RAK3, Q5RCZ8, Q5RD14, Q5W0A0, Q62187, Q6K0P9, Q71F23, Q7RTT3, Q7RTT4, Q7RTT5, Q7RTT6, Q86T96, Q8BV49, Q8BVM9, Q8C0V1, Q8C6C7, Q8CGE8

Diamond homologs: A2XK56, A6NCK2, B8B5U8, P19474, Q0PF16, Q1ACD5, Q1ACD6, Q1ACD7, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3U827, Q3ZEE5, Q587N6, Q587N7, Q5BN31, Q5C8T8, Q5C8U1, Q5C8U3, Q5D7H7, Q5D7H8, Q5D7I0, Q5D7I1, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7I6, Q5D7I9, Q5D7J0, Q5D7J2, Q5RAK3, Q7XI73, Q7XZZ3, Q865W2, Q86T96, Q86XT4, Q8BGE7, Q8GW10, Q8IYM9

SIGNOR signaling

2 interactions.

AEffectBMechanism
Ub:E2“up-regulates activity”RNF180ubiquitination
RNF180“down-regulates quantity by destabilization”ZIC2ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance75
Likely benign9
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1966 predictions. Top by Δscore:

VariantEffectΔscore
5:64165950:ACAGG:Adonor_loss1.0000
5:64165951:CAGG:Cdonor_loss1.0000
5:64165952:AGG:Adonor_loss1.0000
5:64165954:GT:Gdonor_loss1.0000
5:64165955:T:Adonor_loss1.0000
5:64212062:CA:Cacceptor_loss1.0000
5:64212063:A:AGacceptor_gain1.0000
5:64212063:AG:Aacceptor_gain1.0000
5:64212063:AGGAT:Aacceptor_loss1.0000
5:64212064:G:GTacceptor_gain1.0000
5:64212064:GG:Gacceptor_gain1.0000
5:64212064:GGAT:Gacceptor_gain1.0000
5:64212157:AAAA:Adonor_gain1.0000
5:64212158:AAA:Adonor_gain1.0000
5:64212158:AAAG:Adonor_loss1.0000
5:64212159:AA:Adonor_gain1.0000
5:64212160:AG:Adonor_loss1.0000
5:64212161:G:GGdonor_gain1.0000
5:64212161:G:Tdonor_loss1.0000
5:64212162:TAA:Tdonor_loss1.0000
5:64325180:TTGCA:Tacceptor_loss1.0000
5:64325181:TGCA:Tacceptor_loss1.0000
5:64325182:GCA:Gacceptor_loss1.0000
5:64325183:CAGA:Cacceptor_loss1.0000
5:64325184:A:AGacceptor_gain1.0000
5:64325184:A:ATacceptor_loss1.0000
5:64325185:G:GGacceptor_gain1.0000
5:64325185:GA:Gacceptor_gain1.0000
5:64325185:GAC:Gacceptor_gain1.0000
5:64325185:GACT:Gacceptor_gain1.0000

AlphaMissense

3936 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:64325252:T:CC432R1.000
5:64325261:T:CC435R1.000
5:64325366:T:CC470R1.000
5:64325253:G:AC432Y0.999
5:64325254:T:GC432W0.999
5:64325261:T:AC435S0.999
5:64325262:G:AC435Y0.999
5:64325262:G:CC435S0.999
5:64325263:T:GC435W0.999
5:64325291:T:CC445R0.999
5:64325293:T:GC445W0.999
5:64325300:T:CC448R0.999
5:64325301:G:AC448Y0.999
5:64325302:C:GC448W0.999
5:64325312:T:CF452L0.999
5:64325313:T:CF452S0.999
5:64325314:C:AF452L0.999
5:64325314:C:GF452L0.999
5:64325315:T:CC453R0.999
5:64325316:G:AC453Y0.999
5:64325317:T:GC453W0.999
5:64325324:T:CC456R0.999
5:64325326:C:GC456W0.999
5:64325366:T:AC470S0.999
5:64325367:G:AC470Y0.999
5:64325367:G:CC470S0.999
5:64325368:C:GC470W0.999
5:64325375:T:CC473R0.999
5:64325377:T:GC473W0.999
5:64325252:T:AC432S0.998

dbSNP variants (sampled 300 via entrez): RS1000016006 (5:64252000 A>G), RS1000019959 (5:64190521 G>A), RS1000022150 (5:64233948 T>C,G), RS1000026587 (5:64200437 A>C,G), RS1000042652 (5:64325580 T>C), RS1000042662 (5:64329218 A>G), RS1000061898 (5:64202564 A>C,G), RS1000064564 (5:64286189 T>A), RS1000079297 (5:64286489 G>A,T), RS1000098223 (5:64319455 GAGAA>G), RS1000102361 (5:64244948 G>A,T), RS1000111822 (5:64329391 G>A,T), RS1000112433 (5:64330571 G>A), RS1000116661 (5:64234119 T>C), RS1000133905 (5:64337892 A>C,G,T)

Disease associations

OMIM: gene MIM:616015 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

StudyTraitp-value
GCST005951_146Body mass index1.000000e-08
GCST009391_1478Metabolite levels8.000000e-06
GCST011494_18Daytime nap6.000000e-07

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0004340body mass index
EFO:0010464beta-aminoisobutyric acid measurement
EFO:0007828daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Nickeldecreases expression2
methylmercuric chloridedecreases expression1
sodium arseniteincreases expression1
potassium chromate(VI)affects cotreatment, decreases expression1
aflatoxin B2increases methylation1
epigallocatechin gallateaffects cotreatment, decreases expression1
CGP 52608affects binding, increases reaction1
belinostatdecreases expression1
jinfukangaffects cotreatment, decreases expression1
MT19c compoundincreases expression1
Acetaminophendecreases expression1
Arsenicaffects methylation1
Atrazineincreases expression1
Benzo(a)pyrenedecreases methylation1
Cisplatinaffects cotreatment, decreases expression1
Curcumindecreases expression1
Doxorubicindecreases expression1
Triclosandecreases expression1
Valproic Aciddecreases methylation1
Vanadatesdecreases expression1
Aflatoxin B1increases methylation1
Okadaic Aciddecreases expression1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot