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REM2

gene
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Also known as FLJ38964

Summary

REM2 (RRAD and GEM like GTPase 2, HGNC:20248) is a protein-coding gene on chromosome 14q11.2, encoding GTP-binding protein REM 2 (Q8IYK8). Binds GTP saturably and exhibits a low intrinsic rate of GTP hydrolysis.

Predicted to enable GTP binding activity and calcium channel regulator activity. Predicted to be active in plasma membrane.

Source: NCBI Gene 161253 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 52 total — 1 pathogenic
  • MANE Select transcript: NM_173527

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:20248
Approved symbolREM2
NameRRAD and GEM like GTPase 2
Location14q11.2
Locus typegene with protein product
StatusApproved
AliasesFLJ38964
Ensembl geneENSG00000139890
Ensembl biotypeprotein_coding
OMIM616955
Entrez161253

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000267396, ENST00000536884, ENST00000910695

RefSeq mRNA: 1 — MANE Select: NM_173527 NM_173527

CCDS: CCDS45082

Canonical transcript exons

ENST00000267396 — 5 exons

ExonStartEnd
ENSE000009406312288467422885015
ENSE000009406322288526622885339
ENSE000009406332288602422886231
ENSE000012554762288661422887678
ENSE000022800642288322222883390

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 83.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3314 / max 19.5195, expressed in 165 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
1388650.3314165

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
bloodUBERON:000017883.95gold quality
granulocyteCL:000009481.95gold quality
spermCL:000001975.20gold quality
oviduct epitheliumUBERON:000480474.41gold quality
right uterine tubeUBERON:000130274.34gold quality
nucleus accumbensUBERON:000188273.39gold quality
olfactory segment of nasal mucosaUBERON:000538671.72gold quality
pituitary glandUBERON:000000771.15gold quality
spleenUBERON:000210670.75gold quality
adenohypophysisUBERON:000219670.28gold quality
ganglionic eminenceUBERON:000402370.03gold quality
islet of LangerhansUBERON:000000669.11gold quality
caudate nucleusUBERON:000187368.94gold quality
right lungUBERON:000216768.88gold quality
putamenUBERON:000187467.86gold quality
left uterine tubeUBERON:000130366.13gold quality
skin of legUBERON:000151165.14gold quality
cerebellar cortexUBERON:000212965.13gold quality
cerebellar hemisphereUBERON:000224565.09gold quality
right hemisphere of cerebellumUBERON:001489064.97gold quality
bone marrow cellCL:000209264.89silver quality
fallopian tubeUBERON:000388964.86gold quality
bone marrowUBERON:000237164.34gold quality
cerebellumUBERON:000203764.10gold quality
left testisUBERON:000453363.99gold quality
mucosa of stomachUBERON:000119963.81gold quality
skin of abdomenUBERON:000141663.60gold quality
cortical plateUBERON:000534363.27gold quality
right testisUBERON:000453462.95gold quality
nasal cavity mucosaUBERON:000182662.93gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-GEOD-93593yes7.58
E-ANND-3no2.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting REM2, 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-548AN99.9770.912817
HSA-MIR-365899.9673.874379
HSA-MIR-4753-3P99.9071.033786
HSA-MIR-1343-3P99.8966.781815
HSA-MIR-6783-3P99.8967.922059
HSA-MIR-6875-3P99.8270.262983
HSA-MIR-29B-2-5P99.6768.981726
HSA-MIR-568399.3668.592083
HSA-MIR-319698.9663.91326
HSA-MIR-392698.9569.261438
HSA-MIR-471098.6165.961048
HSA-MIR-318098.4664.68348
HSA-MIR-3180-3P98.4664.68348
HSA-MIR-6816-5P98.4664.35364
HSA-MIR-10526-3P97.8664.971342
HSA-MIR-429497.8665.721110
HSA-MIR-443297.8067.87705
HSA-MIR-6782-3P97.6067.75931
HSA-MIR-1288-3P96.8666.95536
HSA-MIR-4740-5P96.2567.96726
HSA-MIR-451595.7065.73716
HSA-MIR-807195.6964.93484
HSA-MIR-3200-3P95.4164.23396
HSA-MIR-448895.3862.00443
HSA-MIR-4697-5P95.3861.72457
HSA-MIR-1237-5P95.3862.21451

Literature-anchored findings (GeneRIF, showing 9)

  • inhibition of L-type Ca2+ channels by Rem2 signaling may represent a new and potentially important mechanism for regulating Ca2+-triggered exocytosis in hormone-secreting cells, including insulin secretion in pancreatic beta-cells (PMID:15728182)
  • data unravel a possible molecular mechanism for Rem2-induced angiogenesis and suggests Rem2 as a potential novel target for treating pathological angiogenesis (PMID:18056257)
  • Rem2 mediates the fibroblastic growth factor 2 (FGF2) signaling pathway to maintain proliferation of hESCsby suppressing the transcriptional activity of p53 and cyclin D(1) (PMID:20231315)
  • our results suggest that Rem2 regulates dendritic branching and synapse development (PMID:21485012)
  • molecular mechanisms by which Rem2 knockdown affected synaptogenesis and Ca(2) homeostasis in cultured rat hippocampal neurons (PMID:21980534)
  • Rem2 has a role in neuronal plasticity hrough co-trafficking with CaMKIIa (PMID:22815963)
  • conclude that endogenous Rem2 is a positive regulator of functional, excitatory synapse development and a negative regulator of dendritic complexity (PMID:23991227)
  • 2 novel gene variants in REM2 and KCNK17 that provide a physiologically plausible explanation for variable expressivity in a large subset of patients in a multigenerational long QT syndrome type 2 family (PMID:29431731)
  • report that substitution of two key amino acid residues in the Rem2 N terminus (Arg-79 and Arg-80) completely abolishes its ability to inhibit CaMKII (PMID:30072381)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriorem2ENSDARG00000074064
mus_musculusRem2ENSMUSG00000022176
rattus_norvegicusRem2ENSRNOG00000011646

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), RERG (ENSG00000134533), 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

GTP-binding protein REM 2 — Q8IYK8 (reviewed: Q8IYK8)

Alternative names: Rad and Gem-like GTP-binding protein 2

All UniProt accessions (1): Q8IYK8

UniProt curated annotations — full annotation on UniProt →

Function. Binds GTP saturably and exhibits a low intrinsic rate of GTP hydrolysis.

Subcellular location. Cell membrane.

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

Isoforms (2)

UniProt IDNamesCanonical?
Q8IYK8-11yes
Q8IYK8-22

RefSeq proteins (1): NP_775798* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001806Small_GTPaseFamily
IPR025662Sigma_54_int_dom_ATP-bd_1Binding_site
IPR027417P-loop_NTPaseHomologous_superfamily
IPR051641RGK_GTP-binding_regFamily

Pfam: PF00071

Enzyme classification (BRENDA):

  • EC 3.4.23.15 — renin (BRENDA: 14 organisms, 40 substrates, 381 inhibitors, 19 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ANGIOTENSINOGEN0.0003–0.00358
4-(4-DIMETHYLAMINOPHENYLAZO)BENZOIC ACID-IHPFHLV0.00361
ACETYL-ASP-ARG-VAL-TYR-ILE-HIS-PRO-PHE-HIS-LEU-L0.121
ARG-GLU(5-[(2-AMINOETHYL)AMINO]-NAPHTHALENE-1-SU0.00641
ARG-GLU(EDANS)-ILE-HIS-PRO-PHE-HIS-LEU-VAL-ILE-H0.01941
RECOMBINANT OVINE ANGIOTENSINOGEN FROM CHO CELLS0.00011
RECOMBINANT OVINE ANGIOTENSINOGEN FROM ESCHERICH0.00011

UniProt features (32 total): helix 8, strand 6, compositionally biased region 4, turn 3, binding site 3, region of interest 2, modified residue 2, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
3CBQX-RAY DIFFRACTION1.82

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8IYK8-F168.190.36

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): 121–128; 229–232; 260–261

Post-translational modifications (2): 27, 295

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): AREB6_03, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, TGACCTY_ERR1_Q2, EFC_Q6, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, CTAGGAA_MIR384, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, AML_Q6, NF1_Q6_01, TGGNNNNNNKCCAR_UNKNOWN, LEF1_Q6, MODULE_48, MODULE_95, GATGKMRGCG_UNKNOWN

GO Biological Process (0):

GO Molecular Function (5): GTPase activity (GO:0003924), calcium channel regulator activity (GO:0005246), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
ribonucleoside triphosphate phosphatase activity1
calcium channel activity1
ion channel regulator activity1
guanyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
nucleoside phosphate binding1
heterocyclic compound binding1
binding1
membrane1
cell periphery1
cellular anatomical structure1

Protein interactions and networks

STRING

1724 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
REM2REM1O75628509
REM2CACNA1BQ00975481
REM2CACNA1CQ13936478
REM2KIF9Q9HAQ2462
REM2CAV2P51636456
REM2CACNA1DQ01668396
REM2PRAMEF18Q5VWM3392
REM2CACNA1AP78510374
REM2CACNA1SQ13698359
REM2CALM1P02593354
REM2CAV1Q03135354
REM2CA10Q9NS85353
REM2RHOP08100349
REM2CA11O75493348
REM2CALML4Q96GE6338

IntAct

8 interactions, top by confidence:

ABTypeScore
CYSRT1REM2psi-mi:“MI:0915”(physical association)0.560
KRTAP1-1REM2psi-mi:“MI:0915”(physical association)0.560
REM2TINF2psi-mi:“MI:0915”(physical association)0.370
REM2CYSRT1psi-mi:“MI:0915”(physical association)0.000
REM2KRTAP1-1psi-mi:“MI:0915”(physical association)0.000

BioGRID (3): KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), REM2 (Two-hybrid)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

Diamond homologs: A2A825, B7ZTR0, Q66JN8, Q6GNL4, Q8IYK8, Q9BU20, Q9WTY2, A1DZY4, A5A6J7, A6NIZ1, A8NU18, C4YKT4, D3Z8L7, G4MZY8, G4N1S3, O35929, O42785, O75628, O88667, O93856, P01119, P03967, P08645, P08647, P0CQ42, P0CQ43, P0CY32, P10114, P10301, P10833, P11233, P11234, P13856, P15064, P18613, P22124, P22126, P22278, P22279, P22280

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance41
Likely benign3
Benign1

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
155681GRCh38/hg38 14q11.2-21.3(chr14:20043513-48642042)x3Pathogenic

SpliceAI

786 predictions. Top by Δscore:

VariantEffectΔscore
14:22885254:A:AGacceptor_gain1.0000
14:22885255:T:Gacceptor_gain1.0000
14:22885257:TCCCA:Tacceptor_loss1.0000
14:22885258:CCCA:Cacceptor_loss1.0000
14:22885259:CCAGC:Cacceptor_loss1.0000
14:22885260:CAGC:Cacceptor_loss1.0000
14:22885261:A:AGacceptor_gain1.0000
14:22885261:A:Tacceptor_loss1.0000
14:22885261:AGCAG:Aacceptor_gain1.0000
14:22885262:G:GAacceptor_gain1.0000
14:22885262:GC:Gacceptor_gain1.0000
14:22885262:GCA:Gacceptor_gain1.0000
14:22885262:GCAGA:Gacceptor_gain1.0000
14:22885264:AGAG:Aacceptor_gain1.0000
14:22885265:GAGG:Gacceptor_gain1.0000
14:22885339:GG:Gdonor_loss1.0000
14:22885340:GTG:Gdonor_loss1.0000
14:22886020:GCAGG:Gacceptor_loss1.0000
14:22886021:CA:Cacceptor_loss1.0000
14:22886022:AG:Aacceptor_gain1.0000
14:22886022:AGG:Aacceptor_gain1.0000
14:22886022:AGGG:Aacceptor_gain1.0000
14:22886022:AGGGG:Aacceptor_gain1.0000
14:22886023:GG:Gacceptor_gain1.0000
14:22886023:GGG:Gacceptor_gain1.0000
14:22886023:GGGG:Gacceptor_gain1.0000
14:22886023:GGGGG:Gacceptor_gain1.0000
14:22883388:CAGG:Cdonor_loss0.9900
14:22883389:AGGT:Adonor_loss0.9900
14:22883391:GTGA:Gdonor_loss0.9900

AlphaMissense

2186 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
14:22886087:T:CF195L1.000
14:22886089:C:AF195L1.000
14:22886089:C:GF195L1.000
14:22886184:T:AV227D1.000
14:22886191:C:AN229K1.000
14:22886191:C:GN229K1.000
14:22886192:A:GK230E1.000
14:22886194:G:CK230N1.000
14:22886194:G:TK230N1.000
14:22884931:G:AG121R0.999
14:22884931:G:CG121R0.999
14:22884931:G:TG121W0.999
14:22884932:G:AG121E0.999
14:22884932:G:TG121V0.999
14:22884946:G:CG126R0.999
14:22884947:G:AG126D0.999
14:22884947:G:TG126V0.999
14:22884949:A:GK127E0.999
14:22884951:G:CK127N0.999
14:22884951:G:TK127N0.999
14:22885320:T:AV167D0.999
14:22886085:T:AV194D0.999
14:22886088:T:CF195S0.999
14:22886090:T:CS196P0.999
14:22886094:T:AV197D0.999
14:22886108:A:CS202R0.999
14:22886110:T:AS202R0.999
14:22886110:T:GS202R0.999
14:22886178:T:AI225N0.999
14:22886178:T:CI225T0.999

dbSNP variants (sampled 300 via entrez): RS1000301415 (14:22887831 A>G), RS1000373201 (14:22884458 G>A), RS1000526895 (14:22883027 G>T), RS1000741557 (14:22886315 T>C), RS1001308106 (14:22881252 G>A,C), RS1001815877 (14:22882202 G>C), RS1001984754 (14:22883267 C>A,T), RS1002101220 (14:22881903 C>G,T), RS1002374143 (14:22887495 G>A), RS1002426249 (14:22887953 G>A), RS1002555834 (14:22883431 G>A), RS1002944364 (14:22882390 A>G), RS1003314167 (14:22884288 T>C), RS1004327347 (14:22883929 T>A), RS1004547941 (14:22885128 A>G)

Disease associations

OMIM: gene MIM:616955 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST010483_2Cardiovascular death, myocardial infarction or stroke in response to clopidogrel treatment5.000000e-06

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0006919cardiovascular event measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

ChemicalActions (top 5)PubMed papers
Tobacco Smoke Pollutiondecreases expression, increases expression2
aristolochic acid Iincreases expression1
sotorasibdecreases expression, affects cotreatment1
triphenyl phosphateaffects expression1
2-methyl-4-isothiazolin-3-oneincreases expression1
15-acetyldeoxynivalenolincreases expression1
di-n-butylphosphoric acidaffects expression1
jinfukangdecreases expression, affects cotreatment1
trametinibaffects cotreatment, decreases expression1
NVP-BKM120affects cotreatment, decreases expression1
Norethindrone Acetateincreases expression, affects cotreatment1
Air Pollutantsaffects expression, increases abundance1
Benzo(a)pyrenedecreases methylation, affects methylation1
Cadmiumdecreases expression, increases abundance1
Cisplatinaffects cotreatment, decreases expression1
Estradiolaffects cotreatment, increases expression1
Methotrexatedecreases expression1
Ozoneincreases abundance, affects expression1
Silverincreases expression1
Smokedecreases expression1
Valproic Aciddecreases expression1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideincreases expression1
Cadmium Chloridedecreases expression, increases abundance1
Okadaic Aciddecreases expression1

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): stroke disorder

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
v1.1.2
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