RAB1A

Summary

RAB1A (RAB1A, member RAS oncogene family, HGNC:9758) is a protein-coding gene on chromosome 2p14, encoding Ras-related protein Rab-1A (P62820). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms.

Source: NCBI Gene 5861 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 19 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_004161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9758
Approved symbol	RAB1A
Name	RAB1A, member RAS oncogene family
Location	2p14
Locus type	gene with protein product
Status	Approved
Aliases	YPT1
Ensembl gene	ENSG00000138069
Ensembl biotype	protein_coding
OMIM	179508
Entrez	5861

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000398529, ENST00000409751, ENST00000409784, ENST00000409892, ENST00000494188, ENST00000649427, ENST00000887624, ENST00000887625, ENST00000887626, ENST00000887627, ENST00000931493, ENST00000931494, ENST00000931495, ENST00000931496, ENST00000970485

RefSeq mRNA: 2 — MANE Select: NM_004161 NM_004161, NM_015543

CCDS: CCDS46305, CCDS46306

Canonical transcript exons

ENST00000409784 — 6 exons

Exon	Start	End
ENSE00000758598	65088939	65089070
ENSE00000758599	65090983	65091078
ENSE00000810194	65097971	65098066
ENSE00001824236	65129893	65130106
ENSE00003490603	65104734	65104806
ENSE00003850387	65086854	65088690

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 150.0251 / max 1285.2682, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28799	150.0072	1827
28800	0.0178	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.72	gold quality
upper leg skin	UBERON:0004262	99.60	gold quality
skin of hip	UBERON:0001554	99.59	gold quality
male germ cell	CL:0000015	99.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.54	gold quality
corpus epididymis	UBERON:0004359	99.49	gold quality
colonic mucosa	UBERON:0000317	99.46	gold quality
amniotic fluid	UBERON:0000173	99.43	gold quality
jejunal mucosa	UBERON:0000399	99.43	gold quality
caput epididymis	UBERON:0004358	99.39	gold quality
adult organism	UBERON:0007023	99.38	gold quality
tibia	UBERON:0000979	99.34	gold quality
oral cavity	UBERON:0000167	99.27	gold quality
palpebral conjunctiva	UBERON:0001812	99.27	gold quality
cartilage tissue	UBERON:0002418	99.26	gold quality
cauda epididymis	UBERON:0004360	99.26	gold quality
heart right ventricle	UBERON:0002080	99.22	gold quality
esophagus squamous epithelium	UBERON:0006920	99.18	gold quality
mammalian vulva	UBERON:0000997	99.15	gold quality
placenta	UBERON:0001987	99.14	gold quality
parietal pleura	UBERON:0002400	99.13	gold quality
pleura	UBERON:0000977	99.12	gold quality
pigmented layer of retina	UBERON:0001782	99.12	gold quality
visceral pleura	UBERON:0002401	99.12	gold quality
bronchial epithelial cell	CL:0002328	99.10	gold quality
pericardium	UBERON:0002407	99.08	gold quality
cardia of stomach	UBERON:0001162	99.07	gold quality
nephron tubule	UBERON:0001231	99.06	gold quality
pylorus	UBERON:0001166	99.01	gold quality
endometrium	UBERON:0001295	99.01	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	39.01
E-MTAB-6075	no	817.86
E-MTAB-6524	no	302.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

184 targeting RAB1A, 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-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• Results indicate that Rab1 and Rab43 are key Rabs required for the biogenesis and maintenance of a functional Golgi structure, and suggest that other Rabs acting at the Golgi complex are likely to be functionally redundant. (PMID:17684057)
• TBC1D20 was found to be the first known GAP for Rab1, which is implicated in the regulation of anterograde traffic between the endoplasmic reticulum and the Golgi complex (PMID:17901050)
• depletion of GM130 by RNA interference slows the rate of ER to Golgi trafficking in vivo; interactions of GM130 with syntaxin 5 and Rab1 are regulated by mitotic phosphorylation (PMID:18167358)
• Results suggest a model where protein trafficking and neuronal differentiation are directly linked by the interaction of Rab1 and its regulator GTRAP3-18. (PMID:18363836)
• Rab 1 S25N mutants efficiently blocked the plasma membrane trafficking of the Kir3.1/Kir3.4 complex however they did not block the Gbeta1gamma2/Kir3.1 interaction. (PMID:19135528)
• Rab1 GTPase and dimerization modulate export traffic from the emndoplasmic reticulum to the cell surface of newly synthesized angiotensin II type 2 receptor. (PMID:19357319)
• Studies determined the crystal structures of Legionella pneumophila SidM alone (residues 317-647) and SidM (residues 193-550) in complex with nucleotide-free WT Rab1. (PMID:20176951)
• Results suggest a novel function for Rab1a in the regulation of cell migration through controlling integrin beta1 recycling and localization to lipid rafts via a specific downstream effector pathway. (PMID:20639577)
• Antibacterial autophagy occurs at omegasomes and reveal that the Rab1 GTPase plays a crucial role in mammalian autophagy. (PMID:20980813)
• Rab1a/b and Rab43, are important for herpes simplex virus 1 virion assembly (PMID:21680502)
• When bound to Rab1, LidA interfered with the covalent modification of Rab1 by phosphocholination or AMPylation, and it also blocked de-AMPylation of Rab1 by SidD and dephosphocholination by Lem3. (PMID:22228731)
• The NS5A interaction with TBC1D20 and Rab1 is essential for the viral life cycle. (PMID:22491470)
• the potential interaction of Rab1 and its effect on export from the endoplasmic reticulum (PMID:22628317)
• analysis of APPL1 and APPL2 proteins and their interaction with Rab (PMID:23055524)
• evidence for a remarkable adaptation of SidD to its host cell target Rab1 which explains how this effector confers specificity to the reaction it catalyses. (PMID:23696742)
• Findings show that Ypt1/Rab1 infindings show that Ypt1/Rab1 interacts with Atg1/Ulk1 in yeast and mammalian cells. (PMID:23716696)
• A major biological consequence of upregulation of miR-221 is reprogramming of androgen receptor signaling via downregulation of HECTD2 and RAB1A. (PMID:23770851)
• Rab1a and Rab5a preferentially bind to binary lipid compositions with higher stored curvature elastic energy. (PMID:23815289)
• The transition state mimetic structure of the Legionella pneumophila GAP LepB in complex with Rab1, is reported. (PMID:23821544)
• Rab1A can rescue the Golgi fragmentation caused by the overabundance of alpha-synuclein in nigral dopaminergic neurons, improving the ability of the surviving neurons to control motor function in hemiparkinsonian animals. (PMID:23939344)
• These data indicate that Rab1a is an important regulator of early endosome sorting for multiple cargo species. (PMID:24407591)
• Rab1A knockdown induced cell death by inhibition of autophagosome formation. (PMID:24801886)
• hyperactive amino acid signaling through Rab1A overexpression drives oncogenesis and renders cancer cells prone to mTORC1-targeted therapy. (PMID:25446900)
• Vaccinia virus can be added to the growing list of viruses which require RAB1A for optimal replication, highlighting this protein as a broadly proviral host factor. (PMID:25462347)
• Rab1A regulates anterograde melanosome transport by recruiting kinesin-1 to melanosomes through interaction with SKIP (PMID:25649263)
• Overexpression of RAB1A is associated with hepatocellular carcinoma. (PMID:26023735)
• Results demonstrate that ALS-mutant forms of TDP-43, FUS, and SOD1 all perturb protein transport in the early secretory pathway between ER and Golgi compartments, and imply that restoring Rab1-mediated ER-Golgi transport is a novel ALS therapeutic target (PMID:26298469)
• Rab1A-dependent activation of mTORC1 has as role in amino acid signaling promotes growth and metastasis of hepatocellular carcinomas (PMID:26308575)
• The ability of Rab1 to regulate WHAMM and the Arp2/3 complex represents a distinct strategy for membrane remodeling in which a Rab G-protein recruits the actin nucleation machinery but dampens its activity. (PMID:26823012)
• Rab1A isoform 3 shows enhanced basal activity and is not controlled by accessory proteins (PMID:26953259)
• As a Rab1a effector, C9orf72 controls initiation of autophagy by regulating the Rab1a-dependent trafficking of the ULK1 autophagy initiation complex to the phagophore. (PMID:27334615)
• For RAB1A, a high accuracy for the discrimination of human hepatocellular carcinoma and nontumorous liver tissue was observed. (PMID:27467182)
• Rab1 is regulated by the host in a similar fashion, and that the innate immunity kinase TAK1 and Legionella effectors compete to regulate Rab1 by switch II modifications during infection. (PMID:27482120)
• In clinical samples, the expression of Rab1A or DHX33 was reversely correlated with miR-634. Re-expression of Rab1A or DHX33 abrogated the miR-634-mediated inhibition of cell proliferation and migration. Collectively, our data suggest a tumor suppressor role of miR-634 in hepatocellular carcinoma. (PMID:27693040)
• Rab1A may be involved in the pathogenesis of human lung cancer in an mTOR- and MAPK-independent manner. (PMID:27902464)
• New Rab1 binding sites have been discovered using an ensemble of clustering methods. (PMID:28120477)
• Upregulation of RAB1A is associated with triple-negative breast cancer. (PMID:28184936)
• Leucine-rich repeat kinase 2 (LRRK2) can interact with several Rab proteins, and such ractions may serve to recruit LRRK2 to distinct subcellular organelles to phosphorylate select substrate proteins involved in membrane trafficking events. (PMID:28202668)
• our data indicate that miR-1202 suppresses proliferation and induces endoplasmic reticulum stress and apoptosis through targeting and inhibiting Rab1A in glioma cells. These results suggest miR-1202 as a potential therapeutic target for the treatment of glioma patients. (PMID:28443461)
• he present study demonstrated that DANCR/miR-634/RAB1A axis plays crucial roles in the progression of glioma, and DANCR might potentially serve as a therapeutic target for the treatment of glioma patients. (PMID:29301870)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rab1a	ENSMUSG00000020149
rattus_norvegicus	Rab1a	ENSRNOG00000004992
drosophila_melanogaster	Rab1	FBGN0285937

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), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955), RAB41 (ENSG00000147127)

Protein

Protein identifiers

Ras-related protein Rab-1A — P62820 (reviewed: P62820)

Alternative names: YPT1-related protein

All UniProt accessions (4): P62820, B7Z8M7, E7END7, Q5U0I6

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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB1A regulates vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment and on to the cell surface, and plays a role in IL-8 and growth hormone secretion. Required to modulate the compacted morphology of the Golgi. Regulates the level of CASR present at the cell membrane. Plays a role in cell adhesion and cell migration, via its role in protein trafficking. Plays a role in autophagosome assembly and cellular defense reactions against pathogenic bacteria. Plays a role in microtubule-dependent protein transport by early endosomes and in anterograde melanosome transport.

Subunit / interactions. May interact with YIPF5. Interacts with C9orf72; the interaction mediates recruitment of RAB1A to the ATG1/ULK1 kinase complex. Interacts with GDI1; this promotes dissociation from membranes. (Microbial infection) Interacts with L.pneumophila AnkX. (Microbial infection) Interacts with L.pneumophila Lem3. (Microbial infection) Interacts with L.pneumophila LidA. (Microbial infection) Interacts with L.pneumophila DrrA; this disrupts the interaction between RAB1A and GDI1 and promotes the exchange of RAB1A-bound GDP with GTP. (Microbial infection) Interacts with E.coli EspG and S.flexneri VirA; this impairs ER to Golgi trafficking and protein secretion. (Microbial infection) Interacts with L.pneumophila and L.drancourtii LepB; this enhances RAB1A GTPase activity. (Microbial infection) Identified in a complex composed of RAB1A, ARF6 and E.coli EspG.

Subcellular location. Golgi apparatus. Endoplasmic reticulum. Early endosome. Cytoplasm. Cytosol. Membrane. Melanosome.

Post-translational modifications. Phosphorylated by CDK1 kinase during mitosis. (Microbial infection) Phosphocholinated at Ser-79 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. Ubiquitinated via ‘Lys-11’-linked ubiquitination on Lys-49 and Lys-61; impairing the recruitment of guanosine diphosphate (GDP) dissociation inhibitor 1/GDI1.

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) which increase 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 drive interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P62820-1	1	yes
P62820-2	2
P62820-3	3

RefSeq proteins (2): NP_004152, NP_056358 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050227	Rab	Family
IPR057289	Rab1/Ypt1	Family

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.

Substrate	Km (mM)	Measurements
GTP	—	0

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (59 total): binding site 17, helix 8, mutagenesis site 7, strand 7, glycosylation site 4, region of interest 3, modified residue 3, lipid moiety-binding region 2, cross-link 2, splice variant 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
2WWX	X-RAY DIFFRACTION	1.5
7EQ2	X-RAY DIFFRACTION	1.55
3SFV	X-RAY DIFFRACTION	1.73
3TKL	X-RAY DIFFRACTION	2.18
2FOL	X-RAY DIFFRACTION	2.63
9MHF	ELECTRON MICROSCOPY	2.73
4JVS	X-RAY DIFFRACTION	2.78
4FMC	X-RAY DIFFRACTION	2.8
3L0I	X-RAY DIFFRACTION	2.85
4FMD	X-RAY DIFFRACTION	3.05
4FMB	X-RAY DIFFRACTION	3.2
4IRU	X-RAY DIFFRACTION	3.2
9MHG	ELECTRON MICROSCOPY	3.2
4FME	X-RAY DIFFRACTION	4.1
9MHH	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62820-F1	85.78	0.70

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 (17): 25; 26; 38; 43; 43; 66; 69; 124; 125; 127; 155; 156 …

Post-translational modifications (7): 2, 79, 194, 204, 205, 49, 61

Glycosylation sites (4): 72, 74, 82, 111

Mutagenesis-validated functional residues (7):

Position	Phenotype
49	promotes tlrs trafficking and tlrs-mediated signaling; when associated with a-61.
61	promotes tlrs trafficking and tlrs-mediated signaling; when associated with a-49.
72–74	abolished arginine glcnacylation; when associated with a-82 and a-111.
74	abolished arginine glcnacylation; when associated with a-82 and a-111.
82	abolished arginine glcnacylation; when associated with a-74 and a-111. abolished arginine glcnacylation; when associated
111	abolished arginine glcnacylation; when associated with a-74 and a-82. abolished arginine glcnacylation; when associated
124	dominant negative mutant. strongly reduces the levels of casr present at the cell-surface.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

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

MSigDB gene sets: 390 (showing top): GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_VACUOLE_ORGANIZATION, MORF_RAB5A, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, DORN_ADENOVIRUS_INFECTION_12HR_UP, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_ENDOTHELIAL_INTESTINAL_BARRIER, GOBP_VESICLE_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP

GO Biological Process (18): autophagosome assembly (GO:0000045), intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), endocytosis (GO:0006897), autophagy (GO:0006914), Golgi organization (GO:0007030), vesicle-mediated transport (GO:0016192), cell migration (GO:0016477), virion assembly (GO:0019068), growth hormone secretion (GO:0030252), melanosome transport (GO:0032402), positive regulation of interleukin-8 production (GO:0032757), substrate adhesion-dependent cell spreading (GO:0034446), defense response to bacterium (GO:0042742), vesicle transport along microtubule (GO:0047496), COPII-coated vesicle cargo loading (GO:0090110), positive regulation of glycoprotein metabolic process (GO:1903020), protein transport (GO:0015031)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), cadherin binding (GO:0045296), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): Golgi membrane (GO:0000139), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endomembrane system (GO:0012505), transport vesicle membrane (GO:0030658), melanosome (GO:0042470), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Mitotic Prophase	1
Golgi-to-ER retrograde transport	1
Post-translational protein modification	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
intracellular transport	3
endomembrane system	3
intracellular protein localization	2
transport	2
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
protein transport	1
intercellular transport	1
Golgi vesicle transport	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
endomembrane system organization	1
cellular process	1
cell motility	1
viral process	1
viral life cycle	1
peptide hormone secretion	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
cell-substrate adhesion	1
defense response	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

194 interactions, top by confidence:

A	B	Type	Score
rep	ISG15	psi-mi:“MI:0914”(association)	0.910
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
RAB1A	GDI1	psi-mi:“MI:0915”(physical association)	0.800
RABIF	RAB3A	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
OCRL	RAB1A	psi-mi:“MI:0915”(physical association)	0.690
RAB1A	OCRL	psi-mi:“MI:0915”(physical association)	0.690
OCRL	RAB1A	psi-mi:“MI:0407”(direct interaction)	0.690
RABIF	RAB1A	psi-mi:“MI:0915”(physical association)	0.670
RAB1A	RABIF	psi-mi:“MI:0915”(physical association)	0.670
RAB1A	drrA	psi-mi:“MI:0407”(direct interaction)	0.670
drrA	RAB1A	psi-mi:“MI:0407”(direct interaction)	0.670
drrA	RAB1A	psi-mi:“MI:0915”(physical association)	0.670
	RAB1A	psi-mi:“MI:0915”(physical association)	0.610
	RAB1A	psi-mi:“MI:0883”(gtpase reaction)	0.610

BioGRID (714): RUSC2 (Two-hybrid), RUSC2 (Reconstituted Complex), RAB1A (Affinity Capture-MS), RAB1A (Affinity Capture-MS), RAB1A (Reconstituted Complex), RAB1A (Affinity Capture-Western), RAB1A (Affinity Capture-MS), RABAC1 (Two-hybrid), RAB1A (Affinity Capture-RNA), ATP1A1 (Co-fractionation), ATP1A2 (Co-fractionation), ATP1A3 (Co-fractionation), ATP1B1 (Co-fractionation), ATP5H (Co-fractionation), BCAP31 (Co-fractionation)

ESM2 similar proteins: A4FV54, F1PTE3, O24466, O42819, P01123, P11620, P17609, P20790, P20791, P22127, P22128, P24409, P31584, P33723, P34139, P34140, P35280, P35281, P35286, P36410, P51153, P55258, P61006, P61007, P61026, P61027, P61028, P62820, P62821, P62822, P70550, Q05974, Q2HJI8, Q39571, Q4R5P1, Q52NJ2, Q54NU2, Q58DS5, Q5F470, Q5KTJ6

Diamond homologs: A4D1S5, A4FV54, F1PTE3, O04486, O24466, O76173, P01123, P10536, P11620, P16976, P17609, P20790, P20791, P22125, P22128, P28186, P28188, P31584, P33723, P34139, P34140, P35280, P35286, P35294, P36410, P36863, P40392, P51153, P51156, P53994, P55258, P59279, P61006, P61007, P61019, P61028, P61105, P62820, P62821, P62822

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
RAB1A	“up-regulates activity”	C9orf72	binding
RAB1A	“up-regulates activity”	ULK1/Atg13/Fip200	binding
CDK1	“down-regulates activity”	RAB1A	phosphorylation
RAB1A	“up-regulates activity”	mTORC1	binding
C9orf72	“up-regulates activity”	RAB1A	binding
RAB1A	“up-regulates activity”	ULK1	relocalization
“TRAPP III complex, TRAPPC2 variant”	“up-regulates activity”	RAB1A	“gtpase-activating protein”
“TRAPP III complex, TRAPPC2B variant”	“up-regulates activity”	RAB1A	“gtpase-activating protein”
RAB1A	“up-regulates activity”	GOLGA2	relocalization
RAB1A	“up-regulates activity”	USO1	binding
MAP3K7	“up-regulates activity”	RAB1A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 173 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:

Pathway	Partners	Fold	FDR
TBC/RABGAPs	7	15.8×	7e-05
RAB geranylgeranylation	8	12.0×	7e-05
NCAM signaling for neurite out-growth	5	11.8×	3e-03
RAB GEFs exchange GTP for GDP on RABs	10	10.8×	2e-05
Regulation of RAS by GAPs	6	10.1×	2e-03
PTEN Regulation	5	9.9×	4e-03
Regulation of PTEN gene transcription	5	7.8×	8e-03
COPII-mediated vesicle transport	5	7.1×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
regulation of long-term neuronal synaptic plasticity	5	34.4×	3e-04
Ras protein signal transduction	8	11.4×	3e-04
positive regulation of fibroblast proliferation	5	10.3×	9e-03
regulation of autophagy	6	10.0×	4e-03
macroautophagy	6	10.0×	4e-03
Golgi organization	8	7.4×	3e-03
exocytosis	7	7.4×	5e-03
endocytosis	10	6.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	10
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3673607	NM_004161.5(RAB1A):c.523C>T (p.Arg175Ter)	Likely pathogenic

SpliceAI

1919 predictions. Top by Δscore:

Variant	Effect	Δscore
2:65074277:TGCA:T	acceptor_loss	1.0000
2:65074280:A:AG	acceptor_gain	1.0000
2:65074280:AGA:A	acceptor_loss	1.0000
2:65074281:G:A	acceptor_loss	1.0000
2:65074281:G:GC	acceptor_gain	1.0000
2:65074281:GA:G	acceptor_gain	1.0000
2:65074281:GAC:G	acceptor_gain	1.0000
2:65074281:GACA:G	acceptor_gain	1.0000
2:65074281:GACAT:G	acceptor_gain	1.0000
2:65074377:TCTC:T	donor_gain	1.0000
2:65077854:T:TA	acceptor_gain	1.0000
2:65077858:A:AG	acceptor_gain	1.0000
2:65077858:AC:A	acceptor_gain	1.0000
2:65077859:C:CA	acceptor_gain	1.0000
2:65077859:C:G	acceptor_gain	1.0000
2:65088688:TTC:T	acceptor_gain	1.0000
2:65088934:CATA:C	donor_loss	1.0000
2:65088935:ATACC:A	donor_loss	1.0000
2:65088936:TACC:T	donor_loss	1.0000
2:65088937:A:C	donor_loss	1.0000
2:65089068:CTC:C	acceptor_gain	1.0000
2:65091075:CCCA:C	acceptor_gain	1.0000
2:65091076:CCA:C	acceptor_gain	1.0000
2:65091076:CCAC:C	acceptor_gain	1.0000
2:65091077:CA:C	acceptor_gain	1.0000
2:65091077:CAC:C	acceptor_gain	1.0000
2:65091079:C:CC	acceptor_gain	1.0000
2:65091082:T:TC	acceptor_gain	1.0000
2:65097964:CACTT:C	donor_loss	1.0000
2:65097965:ACTT:A	donor_loss	1.0000

AlphaMissense

1351 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:65088617:A:G	F165S	1.000
2:65088647:G:T	A155D	1.000
2:65088649:A:C	S154R	1.000
2:65088649:A:T	S154R	1.000
2:65088650:C:A	S154I	1.000
2:65088651:T:G	S154R	1.000
2:65088683:G:T	A143D	1.000
2:65088984:T:A	K125N	1.000
2:65088984:T:G	K125N	1.000
2:65088985:T:A	K125I	1.000
2:65088986:T:C	K125E	1.000
2:65088987:G:C	N124K	1.000
2:65088987:G:T	N124K	1.000
2:65088991:C:A	G123V	1.000
2:65088991:C:T	G123E	1.000
2:65088992:C:A	G123W	1.000
2:65088992:C:G	G123R	1.000
2:65088992:C:T	G123R	1.000
2:65088997:A:G	L121S	1.000
2:65089042:A:G	L106P	1.000
2:65089044:C:A	W105C	1.000
2:65089044:C:G	W105C	1.000
2:65089046:A:G	W105R	1.000
2:65089046:A:T	W105R	1.000
2:65089066:G:A	S98F	1.000
2:65091005:A:T	V89D	1.000
2:65091014:C:T	G86D	1.000
2:65091015:C:G	G86R	1.000
2:65091020:G:T	A84D	1.000
2:65091025:T:A	R82S	1.000

dbSNP variants (sampled 300 via entrez): RS1000058652 (2:65098994 G>A), RS1000095435 (2:65096044 T>C), RS1000140612 (2:65090855 G>A), RS1000149326 (2:65095928 C>A), RS1000259310 (2:65102026 C>T), RS1000282689 (2:65090059 A>C,G), RS1000314326 (2:65093217 T>A,G), RS1000340558 (2:65093473 T>C,G), RS1000357902 (2:65099772 A>C,G), RS1000412366 (2:65107605 A>C), RS1000488941 (2:65115912 T>C,G), RS1000639279 (2:65087299 A>G), RS1000643226 (2:65100485 C>A), RS1000712527 (2:65101813 G>A), RS1000771599 (2:65115718 A>G)

Disease associations

OMIM: gene MIM:179508 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant
complex neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010173_91	Triglyceride levels	1.000000e-10
GCST90002386_249	High light scatter reticulocyte percentage of red cells	2.000000e-09
GCST90002405_127	Reticulocyte count	8.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879826 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.73	Kd	1879	nM	CHEMBL5653589
5.73	ED50	1879	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149170: Binding affinity to human RAB1A incubated for 45 mins by Kinobead based pull down assay	kd	1.8786	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	increases mutagenesis, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression, decreases expression	2
Nanotubes, Carbon	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
ochratoxin A	affects binding	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
nickel acetate	affects expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Bile Acids and Salts	increases expression	1
Cadmium	increases palmitoylation, decreases reaction, increases abundance	1
Caffeine	affects phosphorylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3879681	Binding	Binding affinity to HEK293T cells-derived His-tagged Rab1A expressed in Escherichia coli BL21(DE3) assessed as stoichiometric complex formation at 10 uM after 5 mins by electrospray ionization native mass spectrometry	Affinity-Based Selectivity Profiling of an In-Class Selective Competitive Inhibitor of Acyl Protein Thioesterase 2. — ACS Med Chem Lett

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B3FK	Abcam HEK293T RAB1A KO	Transformed cell line	Female
CVCL_B5KT	HAP1 RAB1A (-) 2	Cancer cell line	Male
CVCL_XS09	HAP1 RAB1A (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice