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RERG

gene
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Also known as MGC15754

Summary

RERG (RAS like estrogen regulated growth inhibitor, HGNC:15980) is a protein-coding gene on chromosome 12p12.3, encoding Ras-related and estrogen-regulated growth inhibitor (Q96A58). Binds GDP/GTP and possesses intrinsic GTPase activity.

RERG, a member of the RAS superfamily of GTPases, inhibits cell proliferation and tumor formation (Finlin et al., 2001 [PubMed 11533059]).

Source: NCBI Gene 85004 — RefSeq curated summary.

At a glance

  • GWAS associations: 17
  • Clinical variants (ClinVar): 31 total
  • MANE Select transcript: NM_032918

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:15980
Approved symbolRERG
NameRAS like estrogen regulated growth inhibitor
Location12p12.3
Locus typegene with protein product
StatusApproved
AliasesMGC15754
Ensembl geneENSG00000134533
Ensembl biotypeprotein_coding
OMIM612664
Entrez85004

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000256953, ENST00000393736, ENST00000437578, ENST00000536465, ENST00000537647, ENST00000537717, ENST00000538313, ENST00000545567, ENST00000546331, ENST00000865193, ENST00000865194, ENST00000965375

RefSeq mRNA: 2 — MANE Select: NM_032918 NM_001190726, NM_032918

CCDS: CCDS53753, CCDS8673

Canonical transcript exons

ENST00000256953 — 5 exons

ExonStartEnd
ENSE000039940851510778315109517
ENSE000039940891512106315121119
ENSE000039940921521742915217603
ENSE000039941011511134415111417
ENSE000039941751522119515221417

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 98.09.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5748 / max 325.5587, expressed in 557 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
1299244.2748518
1299230.6104298
1299200.2701154
1299220.2479146
1299210.171697

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
germinal epithelium of ovaryUBERON:000130498.09gold quality
cauda epididymisUBERON:000436097.67gold quality
body of uterusUBERON:000985397.66gold quality
synovial jointUBERON:000221797.47gold quality
calcaneal tendonUBERON:000370197.36gold quality
left uterine tubeUBERON:000130396.98gold quality
caput epididymisUBERON:000435896.88gold quality
myometriumUBERON:000129696.52gold quality
saphenous veinUBERON:000731896.47gold quality
kidney epitheliumUBERON:000481996.29gold quality
layer of synovial tissueUBERON:000761696.04gold quality
smooth muscle tissueUBERON:000113595.98gold quality
palpebral conjunctivaUBERON:000181295.97gold quality
corpus epididymisUBERON:000435995.81gold quality
descending thoracic aortaUBERON:000234595.76gold quality
epithelium of mammary glandUBERON:000324495.66gold quality
mammary ductUBERON:000176595.63gold quality
superficial temporal arteryUBERON:000161495.41gold quality
parietal pleuraUBERON:000240095.33gold quality
fallopian tubeUBERON:000388994.01gold quality
right uterine tubeUBERON:000130293.97gold quality
popliteal arteryUBERON:000225093.84gold quality
tibial arteryUBERON:000761093.83gold quality
seminal vesicleUBERON:000099893.68gold quality
aortaUBERON:000094793.64gold quality
thoracic aortaUBERON:000151593.41gold quality
mammary glandUBERON:000191193.36gold quality
thoracic mammary glandUBERON:000520093.35gold quality
ascending aortaUBERON:000149693.10gold quality
arteryUBERON:000163793.08gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-CURD-119yes933.46
E-ANND-3yes8.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2C

miRNA regulators (miRDB)

79 targeting RERG, 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-MIR-5011-5P100.0083.465820
HSA-MIR-3163100.0077.238605
HSA-MIR-4476100.0068.182030
HSA-MIR-6876-5P100.0067.682126
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-190A-3P100.0080.355520
HSA-MIR-6870-5P99.9968.552115
HSA-MIR-223-3P99.9970.141140
HSA-MIR-428299.9975.366408
HSA-MIR-186-5P99.9970.833707
HSA-LET-7F-2-3P99.9870.982588
HSA-MIR-1185-1-3P99.9871.042593
HSA-MIR-1185-2-3P99.9871.042593
HSA-MIR-4789-5P99.9870.762721
HSA-MIR-480399.9871.993117
HSA-MIR-4723-5P99.9768.702034
HSA-MIR-569899.9768.492029
HSA-MIR-7111-5P99.9768.482062
HSA-MIR-365899.9673.874379
HSA-MIR-6772-5P99.9467.01577
HSA-MIR-627-3P99.9071.423316
HSA-MIR-380-3P99.8970.181978
HSA-MIR-449599.8272.083080
HSA-MIR-117999.7168.701040
HSA-MIR-5580-3P99.7069.412052
HSA-MIR-379-3P99.6969.601524
HSA-MIR-411-3P99.6969.631524

Literature-anchored findings (GeneRIF, showing 7)

  • Loss of RERG expression is associated with breast cancer and distant metastasis. (PMID:20697807)
  • Results describe the mRNA expression of CRABP1, RERG, and GRP in pituitary adenomas. (PMID:21270509)
  • Estradiol estrogen receptor-beta and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation. (PMID:24992181)
  • this study shows that miR-382-5p expression is negatively correlated with RERG expression, and functions as an independent oncomiR for the higher incidence and poorer prognosis of breast cancer (PMID:27705918)
  • In particular, methylation levels of ITGA4, RERG, and ZNF671 could distinguish Nasopharyngeal carcinoma (NPC) patients from non-cancer nasopharyngeal epithelium (NNE) subjects. We identified the DNA methylation rates of previously unidentified NPC candidate genes. (PMID:28716111)
  • Study revealed that ERK5 can inhibit Raslike oestrogenregulated growth inhibitor (RERG) protein expression and that the inhibition of RERG expression promotes prostatic carcinoma cell proliferation and migration. (PMID:30431143)
  • NF-kappaB-mediated miR-650 plays oncogenic roles and activates AKT/ERK/NF-kappaB pathways by targeting RERG in glioma cells. (PMID:32986146)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_rerioRERGENSDARG00000104632
mus_musculusRergENSMUSG00000030222
rattus_norvegicusRergENSRNOG00000027592

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Protein

Protein identifiers

Ras-related and estrogen-regulated growth inhibitor — Q96A58 (reviewed: Q96A58)

All UniProt accessions (4): Q96A58, F5GWE9, F5GYR1, F5H252

UniProt curated annotations — full annotation on UniProt →

Function. Binds GDP/GTP and possesses intrinsic GTPase activity. Has higher affinity for GDP than for GTP. In cell lines overexpression leads to a reduction in the rate of proliferation, colony formation and in tumorigenic potential.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in heart, brain, placenta, lung, liver, skin, kidney and pancreas. Detected in estrogen receptor-positive breast-derived cell lines, but not in estrogen receptor-negative cell lines. Expression is decreased or lost in a significant proportion of primary breast tumors with poor clinical prognosis.

Induction. Up-regulated by estradiol. Down-regulated by tamoxifen.

Similarity. Belongs to the small GTPase superfamily. Ras family.

Isoforms (2)

UniProt IDNamesCanonical?
Q96A58-11yes
Q96A58-22

RefSeq proteins (2): NP_001177655, NP_116307* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001806Small_GTPaseFamily
IPR005225Small_GTP-bdDomain
IPR027417P-loop_NTPaseHomologous_superfamily
IPR051065Ras-related_GTPaseFamily

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

  • GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (19 total): helix 7, strand 6, binding site 3, chain 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
2ATVX-RAY DIFFRACTION1.9

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96A58-F190.790.76

Functional residue map

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

Ligand- & substrate-binding residues (3): 13–20; 60–64; 118–121

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOZGIT_ESR1_TARGETS_DN, GOBP_GROWTH, CAGCTG_AP4_Q5, PAX8_B, CCANNAGRKGGC_UNKNOWN, CATTTCA_MIR203, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, WANG_LMO4_TARGETS_DN, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (4): small GTPase-mediated signal transduction (GO:0007264), negative regulation of cell population proliferation (GO:0008285), response to hormone (GO:0009725), negative regulation of cell growth (GO:0030308)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), nuclear estrogen receptor binding (GO:0030331), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
negative regulation of cellular process2
guanyl ribonucleotide binding2
intracellular signaling cassette1
cell population proliferation1
regulation of cell population proliferation1
response to endogenous stimulus1
response to chemical1
regulation of cell growth1
cell growth1
negative regulation of growth1
ribonucleoside triphosphate phosphatase activity1
GTPase activity1
molecular function regulator activity1
purine ribonucleoside triphosphate binding1
anion binding1
nuclear receptor binding1
nucleoside phosphate binding1
heterocyclic compound binding1
binding1
catalytic activity1
nucleolus1
intracellular membrane-bounded organelle1
nuclear lumen1
cytoplasm1
membrane1
cell periphery1
intracellular anatomical structure1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RERGESR1P03372545
RERGPHLPP2Q6ZVD8499
RERGABHD14BQ96IU4422
RERGMED7O43513401
RERGINSIG1O15503400
RERGZNF549Q6P9A3399
RERGMETTL6Q8TCB7350
RERGPCMT1P22061349
RERGSPNS3Q6ZMD2348
RERGSPATS1Q496A3344
RERGZFATQ9P243338
RERGLYSMD4Q5XG99337
RERGFBXO36Q8NEA4333
RERGTRARG1Q8IXB3330
RERGGREB1Q4ZG55327

IntAct

4 interactions, top by confidence:

ABTypeScore
RERGARHGEF17psi-mi:“MI:0915”(physical association)0.590
RERGpsi-mi:“MI:0915”(physical association)0.000

BioGRID (4): RERG (Synthetic Lethality), ARHGEF17 (Affinity Capture-MS), RERG (Affinity Capture-RNA), ARHGEF17 (Affinity Capture-MS)

ESM2 similar proteins: A1DZY4, A6QP66, O35626, P0C0E4, P51157, P51158, P55040, P55041, P57729, P63032, P63033, P70425, Q06AU5, Q0VCJ7, Q12829, Q13637, Q19143, Q3SWY9, Q5BJQ5, Q5E9J3, Q5FVY2, Q5R541, Q5RFI2, Q6DGN0, Q6IMA3, Q6IMA7, Q6IMB1, Q6P0U3, Q6T310, Q7TNZ5, Q7YS69, Q8AVS6, Q8QZZ8, Q8R367, Q8TAI7, Q8VHP8, Q8VHQ4, Q8WXH6, Q922H7, Q92730

Diamond homologs: A1DZY4, A6QP66, A8NU18, C4YKT4, O08989, O14807, O35929, O88667, O93856, O94363, P01119, P03967, P08645, P08647, P0CY32, P10114, P10536, P11233, P11234, P15064, P17609, P22124, P22126, P22278, P22279, P22280, P28775, P32254, P36860, P36863, P48555, P59279, P61105, P61225, P61226, P61227, P62070, P62071, P63320, P63321

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance24
Likely benign0
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1607 predictions. Top by Δscore:

VariantEffectΔscore
12:15111431:CAAA:Cacceptor_gain1.0000
12:15121120:C:CCacceptor_gain1.0000
12:15217422:ATCTT:Adonor_loss1.0000
12:15217423:TCTTA:Tdonor_loss1.0000
12:15217424:CTTA:Cdonor_loss1.0000
12:15217425:TTA:Tdonor_loss1.0000
12:15217426:TA:Tdonor_loss1.0000
12:15217427:ACCT:Adonor_loss1.0000
12:15217428:C:CAdonor_loss1.0000
12:15217428:CCTGA:Cdonor_gain1.0000
12:15217603:CCT:Cacceptor_gain1.0000
12:15221190:CTCA:Cdonor_loss1.0000
12:15221191:TCA:Tdonor_loss1.0000
12:15221192:CACC:Cdonor_loss1.0000
12:15221193:A:ACdonor_gain1.0000
12:15221194:C:CCdonor_gain1.0000
12:15110219:T:Adonor_gain0.9900
12:15111416:TT:Tacceptor_gain0.9900
12:15111418:C:CCacceptor_gain0.9900
12:15111426:A:ACacceptor_gain0.9900
12:15111432:A:Tacceptor_gain0.9900
12:15111434:A:Cacceptor_gain0.9900
12:15119301:CAGA:Cacceptor_gain0.9900
12:15119302:A:Tacceptor_gain0.9900
12:15119308:A:ACacceptor_gain0.9900
12:15120541:CATTA:Cdonor_gain0.9900
12:15120545:A:ACdonor_gain0.9900
12:15120629:T:TCacceptor_gain0.9900
12:15121061:A:ACdonor_gain0.9900
12:15121062:C:CCdonor_gain0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000007265 (12:15110867 A>C), RS1000040979 (12:15156325 C>A,T), RS1000096684 (12:15192628 T>A), RS1000121057 (12:15165486 G>A), RS1000143070 (12:15149789 G>A), RS1000200206 (12:15217919 A>G), RS1000275517 (12:15187687 T>C), RS1000282534 (12:15119610 T>C), RS1000284291 (12:15186331 C>G), RS1000339499 (12:15171521 T>C), RS1000342476 (12:15126576 C>T), RS1000346815 (12:15217513 C>G), RS1000449465 (12:15148279 G>C,T), RS1000458934 (12:15181119 C>T), RS1000484641 (12:15179048 A>T)

Disease associations

OMIM: gene MIM:612664 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

StudyTraitp-value
GCST002829_17Urate levels in overweight individuals7.000000e-06
GCST004292_53Glomerular filtration rate (creatinine)1.000000e-07
GCST006630_33Diastolic blood pressure1.000000e-08
GCST007743_27Iris color (L* coordinate)5.000000e-06
GCST007876_4Estimated glomerular filtration rate3.000000e-15
GCST008058_179Estimated glomerular filtration rate1.000000e-31
GCST008059_63Estimated glomerular filtration rate2.000000e-24
GCST008062_95Blood urea nitrogen levels4.000000e-06
GCST008064_23Chronic kidney disease2.000000e-06
GCST008745_35Estimated glomerular filtration rate in non-diabetics2.000000e-11
GCST008747_186Estimated glomerular filtration rate2.000000e-17
GCST008747_74Estimated glomerular filtration rate3.000000e-16
GCST008971_120Urate levels7.000000e-10
GCST90000514_18Gastroesophageal reflux disease1.000000e-09
GCST90002383_49Hematocrit3.000000e-10
GCST90002384_303Hemoglobin3.000000e-10
GCST90002403_446Red blood cell count6.000000e-10

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0004531urate measurement
EFO:0006336diastolic blood pressure
EFO:0009764eye colour measurement
EFO:0004348hematocrit
EFO:0004509hemoglobin measurement
EFO:0004305erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, affects expression7
Estradiolincreases expression, decreases reaction3
trichostatin Aincreases reaction, affects cotreatment, increases expression2
Fulvestrantaffects cotreatment, increases methylation, affects response to substance2
Coumestrolaffects cotreatment, increases expression, affects reaction2
Nickeldecreases expression2
Tobacco Smoke Pollutiondecreases expression2
Tretinoindecreases expression, increases expression2
Particulate Matterdecreases expression, increases abundance2
aristolochic acid Idecreases expression1
methylmercuric chloridedecreases expression1
bisphenol Adecreases expression1
lead acetatedecreases expression1
terbufosincreases methylation1
sulforaphanedecreases expression1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
sodium arsenitedecreases expression1
2,3-bis(3’-hydroxybenzyl)butyrolactoneaffects cotreatment, increases expression1
cupric chloridedecreases expression1
CGP 52608affects binding, increases reaction1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
nutlin 3affects cotreatment, increases expression1
abrinedecreases expression1
dorsomorphinaffects cotreatment, increases expression1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidineincreases expression, increases response to substance1
bisphenol Saffects cotreatment, increases methylation1
jinfukangincreases expression, affects cotreatment1
(+)-JQ1 compounddecreases expression1
Resveratrolaffects cotreatment, increases expression1
Decitabineaffects cotreatment, increases expression, increases reaction1

Clinical trials (associated diseases)

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

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