RAB1B

gene
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Summary

RAB1B (RAB1B, member RAS oncogene family, HGNC:18370) is a protein-coding gene on chromosome 11q13.2, encoding Ras-related protein Rab-1B (Q9H0U4). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. It is a selective cancer dependency (DepMap: 13.0% of cell lines).

Members of the RAB protein family, such as RAB1B, are low molecular mass monomeric GTPases localized on the cytoplasmic surfaces of distinct membrane-bound organelles. RAB1B functions in the early secretory pathway and is essential for vesicle transport between the endoplasmic reticulum (ER) and Golgi (Chen et al., 1997 [PubMed 9030196]; Alvarez et al., 2003 [PubMed 12802079]).

Source: NCBI Gene 81876 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 23 total
  • Cancer dependency (DepMap): dependent in 13.0% of screened cell lines
  • MANE Select transcript: NM_030981

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:18370
Approved symbolRAB1B
NameRAB1B, member RAS oncogene family
Location11q13.2
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000174903
Ensembl biotypeprotein_coding
OMIM612565
Entrez81876

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000311481, ENST00000527397, ENST00000884282, ENST00000884283, ENST00000884284

RefSeq mRNA: 1 — MANE Select: NM_030981 NM_030981

CCDS: CCDS31613

Canonical transcript exons

ENST00000311481 — 6 exons

ExonStartEnd
ENSE000011894196627604466277492
ENSE000011894316627236566272460
ENSE000011894386627215766272252
ENSE000011894436627179766271869
ENSE000021437446626863966268693
ENSE000027127116627580466275935

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 96.0443 / max 419.9149, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
11530580.02901821
11530415.15081796
1153060.8247426
1153030.039814

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of transverse colonUBERON:000499198.58gold quality
lower esophagus mucosaUBERON:003583498.39gold quality
lower esophagusUBERON:001347398.34gold quality
lower esophagus muscularis layerUBERON:003583398.34gold quality
esophagogastric junction muscularis propriaUBERON:003584198.32gold quality
apex of heartUBERON:000209898.26gold quality
skin of legUBERON:000151198.24gold quality
body of stomachUBERON:000116198.19gold quality
gastrocnemiusUBERON:000138898.16gold quality
transverse colonUBERON:000115798.15gold quality
right adrenal glandUBERON:000123398.14gold quality
right coronary arteryUBERON:000162598.10gold quality
right adrenal gland cortexUBERON:003582798.10gold quality
esophagusUBERON:000104398.07gold quality
skin of abdomenUBERON:000141698.06gold quality
left coronary arteryUBERON:000162698.06gold quality
popliteal arteryUBERON:000225098.06gold quality
tibial arteryUBERON:000761098.06gold quality
left adrenal glandUBERON:000123498.05gold quality
muscle layer of sigmoid colonUBERON:003580598.05gold quality
right lungUBERON:000216798.04gold quality
granulocyteCL:000009498.03gold quality
thoracic aortaUBERON:000151598.01gold quality
left adrenal gland cortexUBERON:003582598.01gold quality
mucosa of stomachUBERON:000119998.00gold quality
ascending aortaUBERON:000149697.99gold quality
metanephros cortexUBERON:001053397.99gold quality
aortaUBERON:000094797.98gold quality
minor salivary glandUBERON:000183097.98gold quality
descending thoracic aortaUBERON:000234597.98gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-MTAB-8894no118.62
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting RAB1B, 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-4692100.0067.322066
HSA-MIR-4481100.0066.421669
HSA-MIR-451499.9967.101870
HSA-MIR-548AW99.9972.573559
HSA-MIR-318599.9968.121959
HSA-MIR-103A-3P99.9869.141595
HSA-MIR-10799.9869.141595
HSA-MIR-477599.9875.006394
HSA-MIR-6825-5P99.9669.813431
HSA-MIR-1468-3P99.9672.743797
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-311999.9271.342390
HSA-MIR-7845-5P99.8864.88771
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-132199.8465.301811
HSA-MIR-473999.8465.251832
HSA-MIR-4756-5P99.8464.981809
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-6756-5P99.8267.972466
HSA-MIR-6842-5P99.8067.541587
HSA-MIR-7110-5P99.8067.841712
HSA-MIR-3150A-3P99.7664.441640
HSA-MIR-6763-5P99.7664.681767
HSA-MIR-6764-5P99.7567.892304
HSA-MIR-3913-3P99.7466.53938
HSA-MIR-149-3P99.7268.223963
HSA-MIR-6883-5P99.6968.053785
HSA-MIR-6766-5P99.6867.702325
HSA-MIR-509399.6769.262291
HSA-MIR-317599.6566.302031

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

  • These data support a model where Rab1b-GTP induces GBF1 recruitment at the ERES interface and at the Golgi complex where it is required for COPII/COPI exchange or COPI vesicle formation, respectively. (PMID:17429068)
  • findings show that SidM from Legionella pneumophila could act as both a GDP-GTP exchange factor and GDP-dissociation inhibitor-displacement factor (GDF) for Rab1 (PMID:17947549)
  • The authors demonstrate that Rab1b-activated GBF1 and ARF1 are involved in Ebolavirus virion formation, suggesting that both the COPII and COPI transport systems play a role in Ebolavirus VP40-mediated particle formation. (PMID:20164217)
  • Antibacterial autophagy occurs at omegasomes and reveal that the Rab1 GTPase plays a crucial role in mammalian autophagy. (PMID:20980813)
  • Rab1b is a key regulatory component of COPII dynamics and function. (PMID:21093099)
  • Rab1a/b and Rab43, are important for herpes simplex virus 1 virion assembly (PMID:21680502)
  • results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways (PMID:23188820)
  • The detailed molecular reaction mechanism of a complex between human Rab and RabGAP at the highest possible spatiotemporal resolution and in atomic detail, is described. (PMID:23236136)
  • The crystal structure of the Rab1b-LepB complex. (PMID:23288104)
  • Our results show, for the first time, that changes in Rab1b levels modulate gene transcription and strongly suggest that a Rab1b increase is required to elicit a secretory response. (PMID:23325787)
  • RAB1B acts as a metastasis suppressor in triple-negative breast cancer by regulating the TGF-beta/SMAD signaling pathway and RAB1B may serve as a biomarker of prognosis and response to anti-tumor therapeutics for patients with triple-negative breast cancer. (PMID:25970785)
  • RAB1B localization to the Golgi. (PMID:26977884)
  • Survival analysis indicates that patients with overexpression of Rab1B or MMP9 have significantly worse overall survival and progression-free survival, but better response to chemotherapy than those with low expression of proteins, and that Rab1B is an independent prognostic factor for colorectal cancer patients. (PMID:28316326)
  • In these Rab1B-depleted cells, ATG9A accumulated in intermediate membrane structures at autophagosome formation sites. These results indicate that Rab1B is involved in regulating the proper development of autophagosomes. (PMID:28522593)
  • Rab1b differentially controls the secretion of apolipoproteins and of HCV. (PMID:29020629)
  • ARF5 and Rab1b exhibit RNA-binding capacity, suggesting a role for domain 3 of the IRES in RNA localization into specific cellular compartments. (PMID:30655362)
  • RAB1b interacts with TRAF3 to promote antiviral innate immunity. (PMID:31375559)
  • Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1. (PMID:33469029)
  • LINC00173 facilitates tumor progression by stimulating RAB1B-mediated PA2G4 and SDF4 secretion in nasopharyngeal carcinoma. (PMID:36606322)
  • Circ_RBM23 knockdown suppresses chemoresistance, proliferation, migration and invasion of sorafenib-resistant HCC cells through miR-338-3p/RAB1B axis. (PMID:37075641)
  • Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b. (PMID:37076474)
  • MicroR-380-3p Reduces Sepsis-Induced Acute Kidney Injury via Regulating RAB1P to Restrain NF-kappaB Pathway. (PMID:38220171)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriorab1abENSDARG00000029663
danio_reriorab1aaENSDARG00000052263
mus_musculusRab1bENSMUSG00000024870
rattus_norvegicusRab1bENSRNOG00000050510
rattus_norvegicusRab1bENSRNOG00000070897

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955)

Protein

Protein identifiers

Ras-related protein Rab-1BQ9H0U4 (reviewed: Q9H0U4)

All UniProt accessions (2): Q9H0U4, E9PLD0

UniProt curated annotations — full annotation on UniProt →

Function. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Plays a role in the initial events of the autophagic vacuole development which take place at specialized regions of the endoplasmic reticulum. Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments. Required to modulate the compacted morphology of the Golgi. Promotes the recruitment of lipid phosphatase MTMR6 to the endoplasmic reticulum-Golgi intermediate compartment.

Subunit / interactions. Interacts with MICAL1 and MICAL2. Interacts (in GTP-bound form) with MICALCL, MICAL1 and MILCAL3. Interacts with GDI1; the interaction requires the GDP-bound state. Interacts with CHM/REP1; the interaction requires the GDP-bound form and is necessary for prenylation by GGTase II. Interacts with RabGAP TBC1D20. Interacts (in GDP-bound form) with lipid phosphatase MTMR6 (via GRAM domain); the interaction regulates MTMR6 recruitment to the endoplasmic reticulum-Golgi intermediate compartment. Interacts (in GDP-bound form) with lipid phosphatase MTMR7. (Microbial infection) Interacts with L.pneumophila AnkX. Interacts with L.pneumophila Lem3. Interacts with L.pneumophila SidD. Interacts with L.pneumophila DrrA.

Subcellular location. Cytoplasm. Membrane. Preautophagosomal structure membrane. Perinuclear region.

Post-translational modifications. Prenylated; by GGTase II, only after interaction of the substrate with Rab escort protein 1 (REP1). (Microbial infection) AMPylation at Tyr-77 by L.pneumophila DrrA occurs in the switch 2 region and leads to moderate inactivation of the GTPase activity. It appears to prolong the lifetime of the GTP state of RAB1B by restricting access of GTPase effectors to switch 2 and blocking effector-stimulated GTP hydrolysis, thereby rendering RAB1B constitutively active. It is later de-AMPylated by L.pneumophila SidD, releasing RAB1B from bacterial phagosomes. (Microbial infection) Phosphocholinated at Ser-76 by L.pneumophila AnkX, leading to displace GDP dissociation inhibitors (GDI). Both GDP-bound and GTP-bound forms can be phosphocholinated. Dephosphocholinated by L.pneumophila Lem3, restoring accessibility to L.pneumophila GTPase effector LepB. (Microbial infection) Glycosylated by S.typhimurium protein Ssek3: arginine GlcNAcylation prevents GTPase activity, thereby disrupting vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) including TBC1D20 which increases the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs).

Domain organisation. Switch I, switch II and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drives interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.

Miscellaneous. Rab-1B binds GTP and GDP and possesses low intrinsic GTPase activity.

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

RefSeq proteins (1): NP_112243* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001806Small_GTPaseFamily
IPR005225Small_GTP-bdDomain
IPR027417P-loop_NTPaseHomologous_superfamily
IPR050227RabFamily
IPR057289Rab1/Ypt1Family

Pfam: PF00071

Enzyme classification (BRENDA):

  • EC 3.6.5.2 — small monomeric GTPase (BRENDA: 49 organisms, 138 substrates, 55 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
GTP0

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (63 total): binding site 23, mutagenesis site 11, helix 8, strand 7, region of interest 4, modified residue 4, turn 3, lipid moiety-binding region 2, chain 1

Structure

Experimental structures (PDB)

9 structures.

PDBMethodResolution (Å)
3NKVX-RAY DIFFRACTION1.7
3JZAX-RAY DIFFRACTION1.8
8ALKX-RAY DIFFRACTION2.15
5SZHX-RAY DIFFRACTION2.3
5O74X-RAY DIFFRACTION2.5
4I1OX-RAY DIFFRACTION2.7
5SZKX-RAY DIFFRACTION2.8
6SKUX-RAY DIFFRACTION3.2
4HLQX-RAY DIFFRACTION3.3

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9H0U4-F186.400.71

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 (23): 22; 22; 23; 33; 34; 35; 36; 39; 40; 40; 63; 66

Post-translational modifications (6): 1, 76, 77, 201, 200, 201

Mutagenesis-validated functional residues (11):

PositionPhenotype
67no effect on gdi1 binding. reduces prenylation in vitro, but not in vivo. no effect on interaction with rep1/chm; 100-fo
73abolishes interaction with rep1/chm. no prenylation. much lower gdp/gtp ratio.
76abolishes phosphocholination by legionella ankx.
77abolishes ampylation by legionella drra.
78abolishes interaction with rep1/chm and gdi1. no prenylation. much lower gdp/gtp ratio. no membrane association.
81abolishes interaction with rep1/chm. no prenylation. lowers gdp/gtp ratio by half.
103no effect on prenylation.
110no effect on prenylation.
121prevent formation of autophagosomes.
137no effect on prenylation.
144no effect on prenylation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

IDPathway
R-HSA-162658Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-204005COPII-mediated vesicle transport
R-HSA-6807878COPI-mediated anterograde transport
R-HSA-6811434COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-8873719RAB geranylgeranylation
R-HSA-8876198RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 212 (showing top): GCACCTT_MIR18A_MIR18B, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, WWTAAGGC_UNKNOWN, TGCGCANK_UNKNOWN, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_ENDOTHELIAL_INTESTINAL_BARRIER, LFA1_Q6, AAGCCAT_MIR135A_MIR135B, GCAAGGA_MIR502, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (9): autophagosome assembly (GO:0000045), intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), virion assembly (GO:0019068), positive regulation of glycoprotein metabolic process (GO:1903020), regulation of autophagosome assembly (GO:2000785), autophagy (GO:0006914), protein transport (GO:0015031)

GO Molecular Function (6): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (13): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endomembrane system (GO:0012505), transport vesicle (GO:0030133), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), phagophore assembly site membrane (GO:0034045), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

CategoryPathways
ER to Golgi Anterograde Transport2
Mitotic Prophase1
Golgi-to-ER retrograde transport1
Post-translational protein modification1
Rab regulation of trafficking1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cytoplasm5
cellular anatomical structure5
intracellular protein localization2
intracellular transport2
bounding membrane of organelle2
endomembrane system2
intracellular membrane-bounded organelle2
Atg12 activating enzyme activity1
protein-phosphatidylethanolamide deconjugating activity1
Atg12 conjugating enzyme activity1
Atg12 ligase activity1
organelle assembly1
Atg1/ULK1 kinase complex assembly1
autophagosome organization1
protein transport1
intercellular transport1
Golgi vesicle transport1
organelle organization1
endomembrane system organization1
viral process1
viral life cycle1
glycoprotein metabolic process1
positive regulation of protein metabolic process1
regulation of glycoprotein metabolic process1
autophagosome assembly1
regulation of vacuole organization1
regulation of organelle assembly1
catabolic process1
transmembrane transport1
process utilizing autophagic mechanism1
transport1
establishment of protein localization1
ribonucleoside triphosphate phosphatase activity1
GTPase activity1
molecular function regulator activity1
guanyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
nucleoside phosphate binding1
heterocyclic compound binding1
binding1

Protein interactions and networks

STRING

2303 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RAB1BTBC1D20Q96BZ9916
RAB1BGOLGA2Q08379892
RAB1BPITPNC1Q9UKF7880
RAB1BRUSC2Q8N2Y8866
RAB1BLMAN1P49257851
RAB1BRABIFP47224676
RAB1BCOPB1P53618663
RAB1BLRPAP1P30533595
RAB1BUSO1O60763572
RAB1BMICAL3Q7RTP6568
RAB1BGOLGA5Q8TBA6560
RAB1BTRAPPC8Q9Y2L5542
RAB1BMTMR6Q9Y217537
RAB1BMICAL1Q8TDZ2515
RAB1BGBF1Q92538507

IntAct

127 interactions, top by confidence:

ABTypeScore
GDI1RAB4Apsi-mi:“MI:0914”(association)0.820
RABIFRAB1Bpsi-mi:“MI:0915”(physical association)0.800
LRRK2psi-mi:“MI:0217”(phosphorylation reaction)0.790
RABIFRAB3Apsi-mi:“MI:0914”(association)0.780
CFTRESYT2psi-mi:“MI:2364”(proximity)0.710
RAB1BOCRLpsi-mi:“MI:0407”(direct interaction)0.670
OCRLRAB1Bpsi-mi:“MI:0407”(direct interaction)0.670
RAB8BGDI1psi-mi:“MI:0914”(association)0.640
RAB1Bpsi-mi:“MI:0407”(direct interaction)0.620
LRRK2psi-mi:“MI:0217”(phosphorylation reaction)0.620
LRRK2RAB1Bpsi-mi:“MI:0217”(phosphorylation reaction)0.590
RAB1BRUSC2psi-mi:“MI:0915”(physical association)0.570
RUSC2RAB1Bpsi-mi:“MI:0915”(physical association)0.570
GOLGA2RAB1Bpsi-mi:“MI:0915”(physical association)0.550
PITPNC1RAB1Bpsi-mi:“MI:0915”(physical association)0.540
PITPNC1RAB1Bpsi-mi:“MI:0403”(colocalization)0.540
MAPTKIF2Apsi-mi:“MI:0914”(association)0.530
RAB1ACHMpsi-mi:“MI:0914”(association)0.530
RAB1BCHMpsi-mi:“MI:0914”(association)0.530
RABIFRAB13psi-mi:“MI:0914”(association)0.530

BioGRID (653): RAB1B (Affinity Capture-MS), GDI1 (Affinity Capture-MS), GDI2 (Affinity Capture-MS), RAB1A (Affinity Capture-MS), RAB8B (Affinity Capture-MS), CHML (Affinity Capture-MS), CHM (Affinity Capture-MS), BZW2 (Affinity Capture-MS), RABGGTA (Affinity Capture-MS), RAB33B (Affinity Capture-MS), RAP1GDS1 (Affinity Capture-MS), RAB1B (Affinity Capture-MS), RAB1B (Affinity Capture-MS), ATP1A1 (Co-fractionation), ATP1A3 (Co-fractionation)

ESM2 similar proteins: E2RQ15, O01803, O23561, P05714, P10536, P16976, P20338, P28185, P28188, P31584, P36410, P36861, P40392, P51146, P56371, P57735, P61017, P61018, P61106, P61107, Q05737, Q06AU7, Q2HJH2, Q2TBH7, Q39571, Q40191, Q40520, Q40522, Q40523, Q40723, Q4R8X3, Q52NJ6, Q53B90, Q58DW6, Q5R8Z8, Q5RE13, Q5ZKU5, Q68EK7, Q8CG50, Q91V41

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
RAB geranylgeranylation917.5×6e-07
RAB GEFs exchange GTP for GDP on RABs1013.9×6e-07
Translocation of SLC2A4 (GLUT4) to the plasma membrane610.4×3e-03
ER-Phagosome pathway710.2×1e-03

GO biological processes:

GO termPartnersFoldFDR
exocytosis811.2×6e-04
vesicle-mediated transport87.1×3e-03
endocytosis87.0×3e-03
protein transport135.3×6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance17
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1007 predictions. Top by Δscore:

VariantEffectΔscore
11:66268689:GAATA:Gdonor_gain1.0000
11:66268690:AATA:Adonor_gain1.0000
11:66268691:ATA:Adonor_gain1.0000
11:66268691:ATAGT:Adonor_loss1.0000
11:66268692:TA:Tdonor_gain1.0000
11:66268692:TAGT:Tdonor_loss1.0000
11:66268693:AGT:Adonor_loss1.0000
11:66268694:G:GGdonor_gain1.0000
11:66268695:T:Adonor_loss1.0000
11:66268698:G:GGdonor_gain1.0000
11:66268744:GGGCT:Gdonor_gain1.0000
11:66268745:GGCTG:Gdonor_gain1.0000
11:66271793:CCA:Cacceptor_loss1.0000
11:66271794:CAG:Cacceptor_loss1.0000
11:66271795:A:AGacceptor_gain1.0000
11:66271795:AGT:Aacceptor_gain1.0000
11:66271796:G:GAacceptor_gain1.0000
11:66271796:GT:Gacceptor_gain1.0000
11:66271796:GTG:Gacceptor_gain1.0000
11:66271796:GTGA:Gacceptor_gain1.0000
11:66271796:GTGAC:Gacceptor_gain1.0000
11:66271867:GCT:Gdonor_gain1.0000
11:66271870:G:GGdonor_gain1.0000
11:66271874:G:GGdonor_gain1.0000
11:66272137:ATT:Aacceptor_gain1.0000
11:66272137:ATTG:Aacceptor_gain1.0000
11:66272139:T:Aacceptor_gain1.0000
11:66272146:T:TAacceptor_gain1.0000
11:66272149:A:AGacceptor_gain1.0000
11:66272150:C:Gacceptor_gain1.0000

AlphaMissense

1317 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:66271825:G:CG15R1.000
11:66271825:G:TG15C1.000
11:66271826:G:AG15D1.000
11:66271826:G:TG15V1.000
11:66271840:G:CG20R1.000
11:66271840:G:TG20C1.000
11:66271841:G:AG20D1.000
11:66271841:G:TG20V1.000
11:66271843:A:CK21Q1.000
11:66271844:A:TK21M1.000
11:66271845:G:CK21N1.000
11:66271845:G:TK21N1.000
11:66271847:C:TS22L1.000
11:66271856:T:CL25P1.000
11:66271859:T:CL26P1.000
11:66272184:A:CS39R1.000
11:66272186:C:AS39R1.000
11:66272186:C:GS39R1.000
11:66272188:C:TT40I1.000
11:66272191:T:AI41N1.000
11:66272193:G:AG42R1.000
11:66272193:G:CG42R1.000
11:66272193:G:TG42W1.000
11:66272194:G:AG42E1.000
11:66272194:G:TG42V1.000
11:66272199:G:CD44H1.000
11:66272200:A:GD44G1.000
11:66272200:A:TD44V1.000
11:66272202:T:CF45L1.000
11:66272203:T:CF45S1.000

dbSNP variants (sampled 300 via entrez): RS1000191800 (11:66271613 A>G), RS1000302602 (11:66273055 G>A), RS1000423122 (11:66267715 T>C,G), RS1000529268 (11:66273167 C>T), RS1000628682 (11:66271383 G>T), RS1001003665 (11:66271626 A>G), RS1001305418 (11:66277729 G>A,T), RS1001448336 (11:66267563 A>G), RS1001599826 (11:66268004 C>A), RS1001690799 (11:66272521 T>G), RS1001829341 (11:66267750 A>C), RS1001863620 (11:66272563 G>A), RS1002029262 (11:66267781 G>A), RS1002096887 (11:66274062 C>T), RS1002398632 (11:66271954 G>A,T)

Disease associations

OMIM: gene MIM:612565 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

StudyTraitp-value
GCST001241_12Bipolar disorder2.000000e-07
GCST008103_21Bipolar disorder2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
sodium arsenitedecreases expression, increases abundance, increases expression4
Tobacco Smoke Pollutionaffects expression, increases expression2
triphenyl phosphateaffects expression1
bisphenol Aincreases expression1
sodium arsenatedecreases expression1
pyrogallol 1,3-dimethyl etheraffects cotreatment, affects localization, increases expression1
arseniteincreases abundance, increases expression1
cobaltous chloridedecreases expression1
perfluorooctanoic aciddecreases expression1
ochratoxin Aaffects binding1
cupric oxidedecreases expression1
ochratoxin Baffects binding1
di-n-butylphosphoric acidaffects expression1
monomethylarsonous acidincreases expression1
nutlin 3affects cotreatment, increases secretion1
ICG 001decreases expression1
bisphenol Bincreases expression1
MT19c compounddecreases expression1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-olincreases expression1
bisphenol AFincreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic aciddecreases expression1
Rosiglitazoneincreases expression1
Temozolomidedecreases expression1
Sunitinibdecreases expression1
Azacitidineincreases expression1
Benzo(a)pyrenedecreases expression1
Caffeinedecreases phosphorylation1
Dactinomycinincreases secretion, affects cotreatment1
Bucladesineaffects cotreatment, increases expression1
Diurondecreases expression1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B3FLAbcam HEK293T RAB1B KOTransformed cell lineFemale
CVCL_TH99HAP1 RAB1B (-) 1Cancer cell lineMale
CVCL_TI00HAP1 RAB1B (-) 2Cancer cell lineMale

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.