RAB2A

Summary

RAB2A (RAB2A, member RAS oncogene family, HGNC:9763) is a protein-coding gene on chromosome 8q12.1-q12.2, encoding Ras-related protein Rab-2A (P61019). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

The protein encoded by this gene belongs to the Rab family, members of which are small molecular weight guanosine triphosphatases (GTPases) that contain highly conserved domains involved in GTP binding and hydrolysis. The Rabs are membrane-bound proteins, involved in vesicular fusion and trafficking. This protein is a resident of pre-Golgi intermediates, and is required for protein transport from the endoplasmic reticulum (ER) to the Golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5862 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 26 total
• Druggable target: yes
• MANE Select transcript: NM_002865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9763
Approved symbol	RAB2A
Name	RAB2A, member RAS oncogene family
Location	8q12.1-q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104388
Ensembl biotype	protein_coding
OMIM	179509
Entrez	5862

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000262646, ENST00000396696, ENST00000429861, ENST00000452437, ENST00000466595, ENST00000481569, ENST00000525529, ENST00000529579, ENST00000530071, ENST00000531098, ENST00000531289, ENST00000534260, ENST00000888046, ENST00000888047, ENST00000888048, ENST00000888049, ENST00000888050, ENST00000945840

RefSeq mRNA: 2 — MANE Select: NM_002865 NM_001242644, NM_002865

CCDS: CCDS56537, CCDS6175

Canonical transcript exons

ENST00000262646 — 8 exons

Exon	Start	End
ENSE00001866646	60620674	60623644
ENSE00002187756	60516987	60517253
ENSE00003504417	60558852	60558923
ENSE00003553015	60618580	60618648
ENSE00003569862	60572046	60572113
ENSE00003629515	60584723	60584815
ENSE00003645372	60584208	60584290
ENSE00003682495	60591858	60591969

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 118.5146 / max 1329.5877, expressed in 1827 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89014	69.5718	1824
89017	21.4301	1776
89013	15.7462	1807
89015	7.9275	1766
89016	2.2017	1162
89024	0.5601	175
89023	0.4277	194
89020	0.3347	136
89022	0.3060	89
89019	0.0087	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.96	gold quality
parotid gland	UBERON:0001831	98.90	gold quality
pons	UBERON:0000988	98.75	gold quality
heart right ventricle	UBERON:0002080	98.67	gold quality
postcentral gyrus	UBERON:0002581	98.64	gold quality
cortical plate	UBERON:0005343	98.56	gold quality
islet of Langerhans	UBERON:0000006	98.53	gold quality
parietal lobe	UBERON:0001872	98.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.50	gold quality
entorhinal cortex	UBERON:0002728	98.39	gold quality
superior frontal gyrus	UBERON:0002661	98.38	gold quality
stromal cell of endometrium	CL:0002255	98.37	gold quality
calcaneal tendon	UBERON:0003701	98.36	gold quality
buccal mucosa cell	CL:0002336	98.31	gold quality
tendon	UBERON:0000043	98.18	gold quality
orbitofrontal cortex	UBERON:0004167	98.16	gold quality
myocardium	UBERON:0002349	98.15	gold quality
corpus epididymis	UBERON:0004359	98.12	gold quality
cauda epididymis	UBERON:0004360	98.11	gold quality
lower lobe of lung	UBERON:0008949	98.11	gold quality
superior vestibular nucleus	UBERON:0007227	98.09	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.03	gold quality
vena cava	UBERON:0004087	97.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.96	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.93	gold quality
oral cavity	UBERON:0000167	97.91	gold quality
pharyngeal mucosa	UBERON:0000355	97.87	gold quality
colonic mucosa	UBERON:0000317	97.86	gold quality
CA1 field of hippocampus	UBERON:0003881	97.85	gold quality
caput epididymis	UBERON:0004358	97.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	5.81
E-MTAB-7606	no	1288.05
E-MTAB-6379	no	534.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

214 targeting RAB2A, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302C-5P	99.97	72.56	3642

Literature-anchored findings (GeneRIF, showing 18)

• Rab2 interacts directly with atypical protein kinase C iota/lambda and inhibits aPKCiota/lambda-dependent GADPH phosphorylation (PMID:14570876)
• These data demonstrate that Rab2 and Rab6 differentially influence anterograde transport and signaling of GPCRs. (PMID:17716866)
• ICA69 as a novel Rab2 effector and its role in regulating the early transport of insulin secretory granule proteins (PMID:18187231)
• The results of this study provided that RAB2A and SLC38A1, were associated with the density of calbindin-positive neurons and the number of perineuronal oligodendrocytes in psychiatric disorders. (PMID:20308991)
• The authors identified a specific interaction between the human small GTPase Rab2 and a Brucella spp. protein named RicA. (PMID:21501366)
• first X-ray crystal structure of RicA to 2.7 A resolution and have quantified the affinity of RicA binding to human Rab2 in its GDP-bound and nucleotide-free forms (PMID:24251537)
• As a result of the translocations, RAB2A-PLAG1, the constitutively active promoter of the partner gene drives the ectopic expression of PLAG1. (PMID:24700772)
• Pin1/Rab2A/Erk drives BCSC expansion and tumorigenicity, suggesting potential drug targets. (PMID:25818297)
• The immunohistochemistry-based validation using tissue microarray slides in oral squamous cell carcinoma revealed overexpression of the RAB2A and PRDX1 gene in 80 and 68 % of the tested clinical cases, respectively. (PMID:26159854)
• RAB2A variance has effect on the structure and function of the PFC and related cognitive functions. (PMID:26249043)
• This study demonstrated that RAB2A mutation showing the highest statistical significance in Autism and Schizophrenia. (PMID:26938441)
• our data reveal that RAB2A is new critical membrane trafficking players in the regulation of mesenchymal properties of normal and tumorigenic cells and a critical determinant of an invasive, proteolytic mode of BC progression. (PMID:27255086)
• S100A7 affects cell motility and invasion by regulating the RAB2A-associated MAPK signaling cascades. (PMID:27767088)
• Identify Rab2 as a key factor for autophagic and endocytic cargo delivery to and degradation in lysosomes. (PMID:28483915)
• Bioinformatics were used to determine the target gene of miR192 and Rasrelated protein Rab2A (RAB2A) was identified as a downstream target of miR192. Following the determination of the role of the miR192RAB2A pathway in colon cancer, small molecules that may regulate miR192 were screened and the results demonstrated that simvastatin is an activator of miR192. (PMID:30628692)
• RAB2 regulates the formation of autophagosome and autolysosome in mammalian cells. (PMID:30957628)
• RAB2A promotes cervical cancer progression as revealed by comprehensive analysis of HPV integration and proteome in longitudinal cervical samples. (PMID:35343109)
• Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19. (PMID:37932299)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab2a	ENSDARG00000020261
mus_musculus	Rab2a	ENSMUSG00000047187
rattus_norvegicus	Rab2a	ENSRNOG00000005963
drosophila_melanogaster	Rab2	FBGN0014009
caenorhabditis_elegans	unc-108	WBGENE00006833

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), 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), RAB41 (ENSG00000147127)

Protein

Protein identifiers

Ras-related protein Rab-2A — P61019 (reviewed: P61019)

All UniProt accessions (6): P61019, A0A1D5RMT4, E9PKL7, H0YD31, H0YDL5, H7C125

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 active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology. RAB2A regulates autophagy by promoting autophagosome-lysosome fusion via recruitment of the HOPS endosomal tethering complex; this process involves autophagosomal RAB2A and lysosomal RAB39A recruitment of HOPS subcomplexes VPS39-VPS11 and VPS41-VPS16-VPS18-VPS33A, respectively, which assemble into a functional complex to mediate membrane tethering and SNAREs-driven membrane fusion. Required for protein transport from the endoplasmic reticulum to the Golgi complex. Regulates the compacted morphology of the Golgi. Together with RAB2B, redundantly required for efficient autophagic flux.

Subunit / interactions. Interacts with PRKCI. Interacts with TRIP11. Interacts (in GTP-bound form) with GARIN1B. Interacts (GTP-bound) with HOPS complex component VPS39; interaction contributes to obtaining a functional HOPS complex that promotes autophagosome-lysosome membrane fusion driven by STX17-SNAP29-VAMP8. In contrast with mouse ortholog, not able to interact with VPS41.

Subcellular location. Endoplasmic reticulum-Golgi intermediate compartment membrane. Melanosome. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Autophagosome membrane.

Post-translational modifications. Prenylated. Prenylation is required for association with cellular membranes.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors (GDIs) which inhibit the dissociation of the nucleotide from the GTPase.

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.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P61019-1	1	yes
P61019-2	2

RefSeq proteins (2): NP_001229573, NP_002856* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050209	Rab_GTPases_membrane_traffic	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 (51 total): binding site 26, helix 7, strand 6, short sequence motif 2, lipid moiety-binding region 2, turn 2, initiator methionine 1, chain 1, region of interest 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1Z0A	X-RAY DIFFRACTION	2.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61019-F1	89.51	0.72

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 (26): 19; 19; 20; 20; 20; 21; 21; 38; 38; 61; 64; 119 …

Post-translational modifications (3): 2, 211, 212

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-162658	Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 277 (showing top): RNGTGGGC_UNKNOWN, RRAGTTGT_UNKNOWN, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, HOFMANN_CELL_LYMPHOMA_UP, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GOBP_MEMBRANE_FUSION, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KYNG_DNA_DAMAGE_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, USF_C, TTGCWCAAY_CEBPB_02

GO Biological Process (6): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), macroautophagy (GO:0016236), autophagosome-lysosome fusion (GO:0061909)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (15): Golgi membrane (GO:0000139), autophagosome membrane (GO:0000421), acrosomal vesicle (GO:0001669), nucleus (GO:0005634), lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), melanosome (GO:0042470), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Mitotic Prophase	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
transport	2
guanyl ribonucleotide binding	2
bounding membrane of organelle	2
endomembrane system	2
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
autophagosome assembly	1
autophagy	1
vesicle fusion	1
macroautophagy	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
vacuolar membrane	1
autophagosome	1
secretory granule	1
lysosome	1
lytic vacuole membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum-Golgi intermediate compartment	1
pigment granule	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

210 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
RAB2A	GOLGA2	psi-mi:“MI:0915”(physical association)	0.830
GOLGA2	RAB2A	psi-mi:“MI:0915”(physical association)	0.830
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
RAB2A	FAM114A1	psi-mi:“MI:0915”(physical association)	0.780
BLZF1	RAB2A	psi-mi:“MI:0915”(physical association)	0.780
RAB2A	GARIN6	psi-mi:“MI:0915”(physical association)	0.780
RAB2A	STAMBPL1	psi-mi:“MI:0915”(physical association)	0.780
GARIN6	RAB2A	psi-mi:“MI:0915”(physical association)	0.780
STAMBPL1	RAB2A	psi-mi:“MI:0915”(physical association)	0.780
RAB2A	BLZF1	psi-mi:“MI:0915”(physical association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RAB2A	ICA1	psi-mi:“MI:0915”(physical association)	0.670
ICA1	RAB2A	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (700): RAB2A (Two-hybrid), RAB2A (Two-hybrid), BLZF1 (Two-hybrid), STAMBPL1 (Two-hybrid), FAM114A1 (Two-hybrid), FAM71C (Two-hybrid), RAB2A (Affinity Capture-MS), RAB2A (Affinity Capture-MS), RAB2A (Affinity Capture-MS), RAB2A (Affinity Capture-MS), RAB2A (Affinity Capture-MS), RAB2A (Affinity Capture-MS), RAB2A (Affinity Capture-MS), FAM71C (Two-hybrid), RAB2A (Two-hybrid)

ESM2 similar proteins: O01803, O04486, O18333, O23561, O49513, P05712, P17610, P25766, P36409, P36863, P40393, P49103, P49104, P53994, P59279, P61019, P61105, P61106, P61107, P92963, Q01111, Q01971, Q05975, Q1PEX3, Q38922, Q39434, Q39570, Q39572, Q40193, Q40194, Q40195, Q40521, Q40523, Q40723, Q4R4X6, Q52NJ6, Q5R6B6, Q5R8Z8, Q5ZKU5, Q8WUD1

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

2 interactions.

A	Effect	B	Mechanism
RAB2A	“up-regulates activity”	TRIP11	binding
RAB2A	“down-regulates activity”	PRKCI	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
PD-L1(CD274) glycosylation and translocation to plasma membrane	7	34.0×	1e-07
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	7	22.0×	2e-06
Maturation of spike protein	8	19.9×	7e-07
Maturation of DENV proteins	8	15.8×	3e-06
Defective CFTR causes cystic fibrosis	7	14.4×	3e-05
Hh mutants are degraded by ERAD	6	13.6×	2e-04
ER-Phagosome pathway	11	13.3×	1e-07
Regulation of RUNX3 expression and activity	6	13.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
obsolete protein N-linked glycosylation via asparagine	7	31.0×	2e-06
vesicle fusion	5	19.8×	8e-04
protein N-linked glycosylation	8	13.9×	6e-05
endoplasmic reticulum to Golgi vesicle-mediated transport	9	8.1×	4e-04
Golgi organization	9	7.9×	4e-04
protein transport	15	4.3×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1406 predictions. Top by Δscore:

Variant	Effect	Δscore
8:60517250:ACAG:A	donor_loss	1.0000
8:60517252:AGG:A	donor_loss	1.0000
8:60517254:GTG:G	donor_loss	1.0000
8:60572041:TTTA:T	acceptor_loss	1.0000
8:60572044:A:AC	acceptor_loss	1.0000
8:60572045:G:GT	acceptor_loss	1.0000
8:60572045:GGT:G	acceptor_gain	1.0000
8:60572110:TACGG:T	donor_loss	1.0000
8:60572111:ACGGT:A	donor_loss	1.0000
8:60572114:GT:G	donor_loss	1.0000
8:60572115:T:A	donor_loss	1.0000
8:60572116:AA:A	donor_loss	1.0000
8:60584717:GTTTA:G	acceptor_loss	1.0000
8:60584718:TTTAG:T	acceptor_loss	1.0000
8:60584722:G:GA	acceptor_loss	1.0000
8:60584722:GGA:G	acceptor_gain	1.0000
8:60584722:GGAGA:G	acceptor_gain	1.0000
8:60584811:AAAAG:A	donor_loss	1.0000
8:60584812:AAAG:A	donor_loss	1.0000
8:60584813:AAG:A	donor_loss	1.0000
8:60584814:AG:A	donor_loss	1.0000
8:60584815:GG:G	donor_loss	1.0000
8:60584816:G:C	donor_loss	1.0000
8:60584817:T:A	donor_loss	1.0000
8:60591851:T:G	acceptor_gain	1.0000
8:60591856:A:AG	acceptor_gain	1.0000
8:60591856:AGT:A	acceptor_gain	1.0000
8:60591857:G:GT	acceptor_gain	1.0000
8:60591857:GT:G	acceptor_gain	1.0000
8:60591857:GTG:G	acceptor_gain	1.0000

AlphaMissense

1399 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:60517244:G:C	G13R	1.000
8:60517244:G:T	G13C	1.000
8:60517245:G:A	G13D	1.000
8:60517245:G:T	G13V	1.000
8:60558857:G:C	G18R	1.000
8:60558857:G:T	G18C	1.000
8:60558858:G:A	G18D	1.000
8:60558858:G:T	G18V	1.000
8:60558860:A:C	K19Q	1.000
8:60558861:A:T	K19I	1.000
8:60558862:A:C	K19N	1.000
8:60558862:A:T	K19N	1.000
8:60558864:C:T	S20L	1.000
8:60558896:T:C	F31L	1.000
8:60558898:T:A	F31L	1.000
8:60558898:T:G	F31L	1.000
8:60558918:C:T	T38I	1.000
8:60558923:G:C	G40R	1.000
8:60572046:G:A	G40D	1.000
8:60572054:T:C	F43L	1.000
8:60572056:C:A	F43L	1.000
8:60572056:C:G	F43L	1.000
8:60572097:T:C	L57P	1.000
8:60572103:T:A	I59K	1.000
8:60572103:T:G	I59R	1.000
8:60572105:T:A	W60R	1.000
8:60572105:T:C	W60R	1.000
8:60572107:G:C	W60C	1.000
8:60572107:G:T	W60C	1.000
8:60572108:G:C	D61H	1.000

dbSNP variants (sampled 300 via entrez): RS1000005827 (8:60572713 G>A), RS1000035478 (8:60573021 C>T), RS1000076383 (8:60518411 C>T), RS1000091175 (8:60552106 C>T), RS1000107468 (8:60559881 CAG>C), RS1000124919 (8:60522523 T>A), RS1000166554 (8:60599527 T>G), RS1000184882 (8:60545736 G>C), RS1000196445 (8:60589956 T>C), RS1000258660 (8:60546133 A>T), RS1000261065 (8:60590073 C>T), RS1000305818 (8:60578416 G>A,T), RS1000329768 (8:60539715 G>A), RS1000346447 (8:60607327 G>A), RS1000350917 (8:60583752 T>G)

Disease associations

OMIM: gene MIM:179509 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): CHARGE syndrome (MONDO:0008965)

Orphanet (1): CHARGE syndrome (Orphanet:138)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST008058_272	Estimated glomerular filtration rate	6.000000e-08
GCST009131_15	Systemic sclerosis	4.000000e-08
GCST009145_4	Total cholesterol levels	8.000000e-08
GCST010204_142	Low density lipoprotein cholesterol levels	2.000000e-11
GCST010571_42	Autoimmune thyroid disease	5.000000e-10
GCST90002398_403	Neutrophil count	6.000000e-21
GCST90011899_42	Aspartate aminotransferase levels	9.000000e-16

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004833	neutrophil count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058747	CHARGE Syndrome	C09.218.458.341.186.500.250; C10.597.751.418.341.186.500.250; C10.597.751.941.162.625.250; C11.270.147.500; C11.966.075.375.250; C16.131.077.299.250; C16.320.165; C23.888.592.763.393.341.186.500.500; C23.888.592.763.941.162.625.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105893 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.70	EC50	20	nM	CHEMBL1328505

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases reaction, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
3,4-dihydroxyphenylethanol	increases expression	1
bisphenol A	increases expression	1
titanium dioxide	increases phosphorylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
ochratoxin A	affects binding	1
ochratoxin B	affects binding	1
di-n-butylphosphoric acid	affects expression	1
GW 7604	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
LDN 193189	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, affects reaction, decreases expression, increases reaction	1
Fulvestrant	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aspirin	increases expression	1
Benzo(a)pyrene	decreases expression	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
CHEMBL3992367	Binding	Displacement of BODIPY-GTP from nucleotide binding site of wild-type GST-tagged Rab2 GTPase (unknown origin) after 2 hrs by flow cytometry	Rab7 GTPase inhibitors and related methods of treatment

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B3FM	Abcam HEK293T RAB2A KO	Transformed cell line	Female
CVCL_TI08	HAP1 RAB2A (-) 1	Cancer cell line	Male
CVCL_TI09	HAP1 RAB2A (-) 2	Cancer cell line	Male
CVCL_TI10	HAP1 RAB2A (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT05764980	Not specified	UNKNOWN	Neurovisual Function in CHARGE Syndrome
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT07320482	Not specified	COMPLETED	A Strategic Approach to Safe and Effective Cochlear Implantation in Patients With CHARGE Syndrome