RAB9A

Summary

RAB9A (RAB9A, member RAS oncogene family, HGNC:9792) is a protein-coding gene on chromosome Xp22.2, encoding Ras-related protein Rab-9A (P51151). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Enables G protein activity; GDP binding activity; and GTP binding activity. Involved in positive regulation of exocytosis; receptor-mediated endocytosis; and regulation of protein localization. Located in late endosome; lysosome; and phagocytic vesicle.

Source: NCBI Gene 9367 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 31 total
• Druggable target: yes — 130 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004251

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9792
Approved symbol	RAB9A
Name	RAB9A, member RAS oncogene family
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123595
Ensembl biotype	protein_coding
OMIM	300284
Entrez	9367

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000243325, ENST00000464506, ENST00000618931, ENST00000871509, ENST00000871510, ENST00000871511, ENST00000922880, ENST00000922881, ENST00000922882, ENST00000922883, ENST00000922884, ENST00000922885, ENST00000922886, ENST00000955232, ENST00000955233

RefSeq mRNA: 2 — MANE Select: NM_004251 NM_001195328, NM_004251

CCDS: CCDS14156

Canonical transcript exons

ENST00000464506 — 3 exons

Exon	Start	End
ENSE00001485582	13703814	13703902
ENSE00001822569	13708721	13710504
ENSE00001922339	13689128	13689288

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.8347 / max 560.6972, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195577	30.7014	1823
195578	2.1333	1051

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	97.88	gold quality
parotid gland	UBERON:0001831	95.67	gold quality
endometrium epithelium	UBERON:0004811	95.57	gold quality
adrenal tissue	UBERON:0018303	94.80	gold quality
palpebral conjunctiva	UBERON:0001812	94.77	gold quality
corpus callosum	UBERON:0002336	93.95	gold quality
right adrenal gland cortex	UBERON:0035827	93.94	gold quality
skin of hip	UBERON:0001554	93.92	gold quality
epithelium of nasopharynx	UBERON:0001951	93.76	gold quality
left adrenal gland	UBERON:0001234	93.72	gold quality
right adrenal gland	UBERON:0001233	93.56	gold quality
adrenal cortex	UBERON:0001235	93.53	gold quality
upper leg skin	UBERON:0004262	93.41	gold quality
adrenal gland	UBERON:0002369	93.34	gold quality
left adrenal gland cortex	UBERON:0035825	93.31	gold quality
pancreatic ductal cell	CL:0002079	93.12	gold quality
oral cavity	UBERON:0000167	93.00	gold quality
calcaneal tendon	UBERON:0003701	92.93	gold quality
heart right ventricle	UBERON:0002080	92.91	gold quality
pharyngeal mucosa	UBERON:0000355	92.88	gold quality
nasal cavity mucosa	UBERON:0001826	92.67	gold quality
islet of Langerhans	UBERON:0000006	92.65	gold quality
penis	UBERON:0000989	92.58	gold quality
nasal cavity epithelium	UBERON:0005384	92.56	gold quality
colonic mucosa	UBERON:0000317	92.52	gold quality
pericardium	UBERON:0002407	92.39	gold quality
synovial joint	UBERON:0002217	92.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.00	gold quality
spinal cord	UBERON:0002240	91.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	10.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARD

miRNA regulators (miRDB)

45 targeting RAB9A, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-5571-5P	99.49	66.99	1764

Literature-anchored findings (GeneRIF, showing 24)

• Data show that ectopic expression of human telomerase reverse transcriptase (hTeRT) in human cells leads to an upregulation of the small GTPase Rab9 and its effector p40. (PMID:12576506)
• The overall structure shows a characteristic nucleotide binding fold consisting of a six-stranded beta-sheet surrounded by five alpha-helices with a tightly bound GDP molecule in the active site. (PMID:15263003)
• cholesterol contributes directly to the sequestration of Rab9 on Niemann-Pick type C cell membranes, which in turn, disrupts mannose 6-phosphate receptor trafficking (PMID:16644737)
• Binding of the effector protein TIP47 is important for Rab9 localization. (PMID:16769818)
• Rab9 interacts with the intermediate filament vimentin. This interaction is altered by lipid accumulation in late endosomes, which results in inhibition of protein kinase C and hypophosphorylation of vimentin, leading to late endosome dysfunction. (PMID:18681838)
• VV p37 protein associates with host TIP47, Rab9 and CI-MPR. (PMID:19400954)
• Data indicate that human copper transporter 1 cleavage occurs in a late endosomal, Rab9-positive compartment prior to delivery of the transporter to the plasma membrane. (PMID:19684018)
• Data show that recombinant HPS1-HPS4 produced in insect cells can be efficiently isolated as a 1:1 heterodimer, and might function as a Rab9 effector in the biogenesis of lysosome-related organelles. (PMID:20048159)
• Results describe the involvement of two Rab GTPases, Rab9 and Rab11, in the trafficking of TRPC6. (PMID:20346379)
• RUTBC1 is a Tre2/Bub2/Cdc16 domain-containing protein that binds to Rab9A-GTP both in vitro and in cultured cells, but is not a GTPase-activating protein for Rab9A. (PMID:21808068)
• Rab9A and Rab23 GTPases play crucial roles in autophagy of Group A Streptococcus. (PMID:22452336)
• These data show that RUTBC2 can act as a Rab36 GAP in cells and suggest that RUTBC2 links Rab9A function to Rab36 function in the endosomal system. (PMID:22637480)
• Rab9a and Rab7b are mediators of the transit of the L2 capsid protien and the pseudogenome of human papillomavirus 16 from the late endosome to the golgi complex. (PMID:23345514)
• Rab9-complexed TIP47 plays an essential role for the proper release of hepatitis C viral particles. (PMID:24480419)
• Rab9A and its co-regulatory GTPases control STX13-mediated cargo delivery to maturing melanosomes. (PMID:26527546)
• RAB9 competes with the catalytic subunit PPP2CA in binding to PPP2R1A. This competitive association has an important role in controlling the PP2A catalytic activity. (PMID:27611305)
• protein kinase C modulates alpha1B-adrenergic receptor transfer to late endosomes and that Rab9 regulates this process and participates in G protein-mediated signaling turn-off. (PMID:28082304)
• Authors predicted the binding between RAB9A and miR-150-5p, and the direct interaction between RAB9A and miR-150-5p was confirmed by luciferase reporter and RNA immunoprecipitation assays. We also showed that RAB9A expression was regulated negatively by miR-150-5p, but was regulated positively by ZFAS1. (PMID:30889053)
• Knockdown of Rab9 Suppresses the Progression of Gastric Cancer Through Regulation of Akt Signaling Pathway. (PMID:32301398)
• RAB9A Plays an Oncogenic Role in Human Liver Cancer Cells. (PMID:32420351)
• Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532-3p/RAB9A signal under hypoxia. (PMID:33862456)
• Rab9 Mediates Pancreatic Autophagy Switch From Canonical to Noncanonical, Aggravating Experimental Pancreatitis. (PMID:34610499)
• Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. (PMID:37703297)
• CALCOCO2/NDP52 associates with RAB9 to initiate an antiviral response to hepatitis B virus infection through a lysosomal degradation pathway. (PMID:38752371)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab9a	ENSDARG00000045027
mus_musculus	Rab9	ENSMUSG00000079316
rattus_norvegicus	Rab9a	ENSRNOG00000030443

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), 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-9A — P51151 (reviewed: P51151)

All UniProt accessions (2): A0A1B0GUI0, P51151

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. RAB9A is involved in the transport of proteins between the endosomes and the trans-Golgi network (TGN). Specifically uses NDE1/NDEL1 as an effector to interact with the dynein motor complex in order to control retrograde trafficking of RAB9-associated late endosomes to the TGN. Involved in the recruitment of SGSM2 to melanosomes and is required for the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes.

Subunit / interactions. Interacts (preferentially in its GTP-bound form) with GCC2 (via its GRIP domain). Interacts (GTP-bound form) with SGSM1; the GDP-bound form has much lower affinity for SGSM1. Interacts with SGSM2. The GTP-bound form but not the GDP-bound form interacts with HPS4 and BLOC-3 complex (heterodimer of HPS1 and HPS4) but does not interact with HPS1 alone. Interacts (GTP-bound form) with NDE1; two RAB9A-GTP molecules lie on the opposite sides of the NDE1 homodimer; the interaction leads to RAB9A-dynein motor tethering. Interacts (GTP-bound form) with NDEL1.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane. Late endosome. Cytoplasmic vesicle. Phagosome membrane. Phagosome. Cytoplasmic vesicle membrane. Melanosome.

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 1, switch 2 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.

RefSeq proteins (2): NP_001182257, NP_004242* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041824	Rab9	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (63 total): binding site 28, mutagenesis site 10, helix 8, strand 6, modified residue 3, short sequence motif 2, lipid moiety-binding region 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1WMS	X-RAY DIFFRACTION	1.25
7E1T	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51151-F1	91.41	0.79

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 (28): 20; 21; 21; 21; 22; 22; 34; 38; 39; 39; 62; 65 …

Post-translational modifications (5): 2, 179, 187, 200, 201

Mutagenesis-validated functional residues (10):

Position	Phenotype
40	loss of interaction with hps4; when associated with l-66.
40	loss of interaction with nde1 and the dynein complex. loss of localization to intracellular membrane vesicles.
43	decreased interaction with nde1.
44	loss of interaction with nde1 and the dynein complex. loss of localization to intracellular membrane vesicles.
44	loss of interaction with hps4; when associated with l-66.
46	loss of interaction with nde1.
61	loss of interaction with nde1. no change in localization to intracellular membrane vesicles.
61	loss of interaction with hps4; when associated with l-66.
66	loss of interaction with hps4; when associated with l-40 or l-44 or l-61.
72	loss of interaction with nde1 and the dynein complex. loss of localization to intracellular membrane vesicles.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-9706019	RHOBTB3 ATPase cycle

MSigDB gene sets: 238 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, MORF_RAB5A, WHITEHURST_PACLITAXEL_SENSITIVITY, KAAB_FAILED_HEART_ATRIUM_DN, HOFMANN_CELL_LYMPHOMA_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MORF_PSMC2, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, MISSIAGLIA_REGULATED_BY_METHYLATION_UP

GO Biological Process (6): receptor-mediated endocytosis (GO:0006898), protein transport (GO:0015031), Rab protein signal transduction (GO:0032482), regulation of protein localization (GO:0032880), retrograde transport, endosome to Golgi (GO:0042147), positive regulation of exocytosis (GO:0045921)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (19): Golgi membrane (GO:0000139), lysosome (GO:0005764), late endosome (GO:0005770), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), transport vesicle (GO:0030133), phagocytic vesicle membrane (GO:0030670), trans-Golgi network membrane (GO:0032588), melanosome (GO:0042470), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Post-translational protein modification	1
Rab regulation of trafficking	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
endomembrane system	4
cytoplasmic vesicle	3
intracellular protein localization	2
guanyl ribonucleotide binding	2
organelle membrane	2
cellular anatomical structure	2
membrane	2
intracellular membrane-bounded organelle	2
endocytosis	1
transport	1
establishment of protein localization	1
small GTPase-mediated signal transduction	1
regulation of localization	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
exocytosis	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
lytic vacuole	1
endosome	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cell periphery	1
endocytic vesicle membrane	1
phagocytic vesicle	1
trans-Golgi network	1

Protein interactions and networks

STRING

1716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB9A	GCC2	Q8IWJ2	771
RAB9A	SGSM2	O43147	691
RAB9A	STX12	Q86Y82	636
RAB9A	TBC1D15	Q8TC07	598
RAB9A	PLIN3	O60664	582
RAB9A	DENND2A	Q9ULE3	574
RAB9A	RHOBTB3	O94955	562
RAB9A	TRAPPC2	P0DI81	559
RAB9A	YKT6	O15498	553
RAB9A	GPM6B	Q13491	491
RAB9A	VPS35	Q96QK1	487
RAB9A	RAB4A	P20338	474
RAB9A	EEA1	Q15075	472
RAB9A	VPS29	Q9UBQ0	470
RAB9A	SCAMP1	O15126	460

IntAct

204 interactions, top by confidence:

A	B	Type	Score
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
RAB9A	GDI1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NISCH	RAB9A	psi-mi:“MI:0915”(physical association)	0.690
RAB9A	CHM	psi-mi:“MI:2364”(proximity)	0.610
RAB9A	CHM	psi-mi:“MI:0914”(association)	0.610
	RAB9A	psi-mi:“MI:0407”(direct interaction)	0.590
RAB9A	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.570
RAB9A	sifA	psi-mi:“MI:0915”(physical association)	0.560
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
RCVRN	RAB9A	psi-mi:“MI:0914”(association)	0.530
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PI4K2A	GABARAP	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
HPS4	RAB9A	psi-mi:“MI:0915”(physical association)	0.480
	RAB9A	psi-mi:“MI:0407”(direct interaction)	0.440
RAB9A	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
RAB9A	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF12	RAB9A	psi-mi:“MI:0407”(direct interaction)	0.440
RAB9A	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
RAB9A	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (729): RAB9A (Affinity Capture-MS), RAB9A (Affinity Capture-MS), RAB9A (Affinity Capture-MS), RAB9A (Affinity Capture-MS), RAB9A (Affinity Capture-MS), RAB9A (Proximity Label-MS), RAB9A (Affinity Capture-MS), RAB9A (Affinity Capture-MS), RABEPK (Two-hybrid), RAB9A (Affinity Capture-MS), GDI1 (Affinity Capture-MS), CHML (Affinity Capture-MS), CHM (Affinity Capture-MS), RABGGTA (Affinity Capture-MS), GDI2 (Affinity Capture-MS)

ESM2 similar proteins: A5D7F5, C8VQY7, G4MYS1, H9BW96, I1RMF2, O04157, O24461, O76742, O94655, O97572, P09527, P18067, P24408, P31022, P36411, P36864, P51149, P51150, P51151, P91580, P93267, P97950, Q14088, Q39573, Q3T0F5, Q40787, Q41640, Q43463, Q54QR3, Q5M7D1, Q5R615, Q5R9Y4, Q5RDE5, Q5ZHV1, Q6IMK3, Q6IML7, Q6IMM1, Q7ZYF1, Q8CFP6, Q948K8

Diamond homologs: A2WSI7, A2Y7R5, A2YEQ6, H9BW96, O17915, O76742, O97572, P09527, P18067, P22127, P24408, P24409, P28748, P32835, P32836, P33519, P34139, P35288, P36411, P36864, P38542, P38543, P38544, P38545, P38546, P38547, P38548, P41914, P41915, P41916, P41917, P41918, P41919, P42558, P51149, P51150, P51151, P52301, P54765, P54766

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RAB9A	“up-regulates activity”	GCC2
RAB9A	“up-regulates activity”	RABEPK
RAB9A	“up-regulates activity”	PLIN3

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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
Ras activation upon Ca2+ influx through NMDA receptor	5	25.5×	1e-04
Unblocking of NMDA receptors, glutamate binding and activation	5	24.3×	1e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	24.3×	1e-04
Long-term potentiation	5	21.2×	2e-04
Assembly and cell surface presentation of NMDA receptors	8	18.1×	2e-06
Neurexins and neuroligins	10	17.6×	8e-08
Protein-protein interactions at synapses	6	14.2×	2e-04
RND3 GTPase cycle	6	13.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	12	45.0×	1e-14
protein localization to synapse	6	29.6×	6e-06
receptor clustering	7	28.2×	1e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	22.4×	5e-06
canonical NF-kappaB signal transduction	5	11.8×	4e-03
autophagosome maturation	5	11.3×	5e-03
protein-containing complex assembly	9	6.6×	8e-04
cell-cell adhesion	10	6.5×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

528 predictions. Top by Δscore:

Variant	Effect	Δscore
X:13708719:AG:A	acceptor_gain	1.0000
X:13708720:GG:G	acceptor_gain	1.0000
X:13689288:GGTG:G	donor_loss	0.9900
X:13689289:GTGAG:G	donor_loss	0.9900
X:13689290:T:A	donor_loss	0.9900
X:13708715:TTACA:T	acceptor_loss	0.9900
X:13708716:TACA:T	acceptor_loss	0.9900
X:13708719:A:AG	acceptor_gain	0.9900
X:13708719:A:T	acceptor_loss	0.9900
X:13708720:G:GG	acceptor_gain	0.9900
X:13708720:G:T	acceptor_loss	0.9900
X:13708720:GGGTT:G	acceptor_gain	0.9900
X:13689284:GCGAG:G	donor_gain	0.9800
X:13708719:AGG:A	acceptor_gain	0.9800
X:13708720:GGG:G	acceptor_gain	0.9800
X:13708717:ACAG:A	acceptor_gain	0.9700
X:13689289:G:GG	donor_gain	0.9600
X:13708713:TTTTA:T	acceptor_loss	0.9600
X:13689286:GAG:G	donor_gain	0.9500
X:13689267:T:TA	donor_gain	0.9400
X:13708714:TTTAC:T	acceptor_loss	0.9400
X:13708720:GGGT:G	acceptor_gain	0.9400
X:13689291:GA:G	donor_loss	0.9200
X:13709112:G:A	acceptor_gain	0.9200
X:13703729:CTGA:C	acceptor_gain	0.8800
X:13689210:C:A	donor_gain	0.8700
X:13690617:T:G	acceptor_gain	0.8600
X:13697868:G:GT	donor_gain	0.8600
X:13698856:T:TA	donor_gain	0.8500
X:13706215:A:T	donor_gain	0.8400

AlphaMissense

1332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:13708931:A:C	D62A	1.000
X:13708931:A:T	D62V	1.000
X:13708805:A:T	K20M	0.999
X:13708876:T:C	F44L	0.999
X:13708878:T:A	F44L	0.999
X:13708878:T:G	F44L	0.999
X:13708927:T:A	W61R	0.999
X:13708927:T:C	W61R	0.999
X:13708930:G:C	D62H	0.999
X:13708931:A:G	D62G	0.999
X:13708932:C:A	D62E	0.999
X:13708932:C:G	D62E	0.999
X:13708951:T:C	F69L	0.999
X:13708953:C:A	F69L	0.999
X:13708953:C:G	F69L	0.999
X:13708995:C:G	C83W	0.999
X:13708786:G:A	G14R	0.998
X:13708786:G:C	G14R	0.998
X:13708787:G:A	G14E	0.998
X:13708787:G:T	G14V	0.998
X:13708801:G:A	G19R	0.998
X:13708801:G:C	G19R	0.998
X:13708801:G:T	G19W	0.998
X:13708802:G:A	G19E	0.998
X:13708804:A:C	K20Q	0.998
X:13708806:G:C	K20N	0.998
X:13708806:G:T	K20N	0.998
X:13708840:T:C	F32L	0.998
X:13708842:T:A	F32L	0.998
X:13708842:T:G	F32L	0.998

dbSNP variants (sampled 300 via entrez): RS1000023752 (X:13702449 T>C), RS1000913603 (X:13699354 A>G), RS1000950103 (X:13702781 C>A), RS1001024363 (X:13699902 A>G), RS1001149265 (X:13688562 C>G), RS1001156127 (X:13694666 G>A), RS1001204007 (X:13696075 A>G), RS1001205067 (X:13703114 G>C), RS1001381139 (X:13703201 A>G), RS1001388441 (X:13689168 G>A,C,T), RS1001487941 (X:13696638 A>G), RS1001497563 (X:13689107 G>A,T), RS1002088887 (X:13700083 G>A), RS1002258812 (X:13689462 T>G), RS1002932931 (X:13693413 A>G)

Disease associations

OMIM: gene MIM:300284 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002404_417	Red cell distribution width	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293294 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

130 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 781,252 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1070	NABUMETONE	4	55,063
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1096	AMLEXANOX	4	4,195
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1177	PEMOLINE	4	12,716
CHEMBL1200791	OXYMETAZOLINE HYDROCHLORIDE	4	4,582
CHEMBL1200930	RABEPRAZOLE SODIUM	4	3,361
CHEMBL1215	PHENYLEPHRINE	4	37,782
CHEMBL1228	OXYPHENBUTAZONE ANHYDROUS	4	24,044
CHEMBL1233	CARISOPRODOL	4	37,387
CHEMBL1255654	TETRACAINE HYDROCHLORIDE	4	5,419
CHEMBL1274	NILUTAMIDE	4	64,154
CHEMBL1356238	PYRITHIONE	4	15,582
CHEMBL1375743	ZIPRASIDONE HYDROCHLORIDE	4	7,696
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL1448	NICLOSAMIDE	4
CHEMBL1454910	NITROXOLINE	4
CHEMBL1467	ALLOPURINOL	4
CHEMBL1484	NICARDIPINE	4
CHEMBL1489	AZACITIDINE	4
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4
CHEMBL157101	KETOCONAZOLE	4
CHEMBL15870	INDOPROFEN	4
CHEMBL17157	TERFENADINE	4
CHEMBL1751	DIGOXIN	4

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

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Potency	1	nM	CHEMBL1339678
9.00	Potency	1	nM	CHEMBL1352801
8.89	Potency	1.3	nM	CHEMBL1339143
8.89	Potency	1.3	nM	CHEMBL1402010
8.49	Potency	3.2	nM	CHEMBL3194248
8.49	Potency	3.2	nM	CHEMBL1492399
8.49	Potency	3.2	nM	CHEMBL1519965
8.49	Potency	3.2	nM	CHEMBL1320414
8.20	Potency	6.3	nM	CHEMBL1303280
8.20	Potency	6.3	nM	CHEMBL1526049
8.10	Potency	7.9	nM	CHEMBL3145312
8.00	Potency	10	nM	CHEMBL1579338
8.00	Potency	10	nM	CHEMBL1326315
8.00	Potency	10	nM	CHEMBL1352521
7.90	Potency	12.6	nM	CHEMBL1584650
7.80	Potency	15.8	nM	CHEMBL1602086
7.80	Potency	15.8	nM	CHEMBL1606641
7.70	Potency	20	nM	CHEMBL1594991
7.60	Potency	25.1	nM	CHEMBL1564713
7.60	Potency	25.1	nM	CHEMBL1349442
7.60	Potency	25.1	nM	CHEMBL1506796
7.55	Potency	28.2	nM	CHEMBL1405122
7.55	Potency	28.2	nM	CHEMBL3194739
7.50	Potency	31.6	nM	CHEMBL1556128
7.50	Potency	31.6	nM	CHEMBL1612044
7.50	Potency	31.6	nM	CHEMBL1305475
7.50	Potency	31.6	nM	CHEMBL1385865
7.50	Potency	31.6	nM	CHEMBL3190397
7.45	Potency	35.5	nM	CHEMBL3193405
7.45	Potency	35.5	nM	CHEMBL1479301
7.40	Potency	39.8	nM	CHEMBL1496375
7.40	Potency	39.8	nM	CHEMBL1486109
7.40	Potency	39.8	nM	CHEMBL1549310
7.30	Potency	50.1	nM	CHEMBL1513046
7.15	Potency	70.8	nM	CHEMBL267630
7.15	Potency	70.8	nM	CHEMBL1325943
7.10	Potency	79.4	nM	CHEMBL1597245
7.10	Potency	79.4	nM	CHEMBL1315904
7.10	Potency	79.4	nM	CHEMBL3189541
7.10	Potency	79.4	nM	CHEMBL3191171
7.10	Potency	79.4	nM	CHEMBL3210983
7.10	Potency	79.4	nM	NICLOSAMIDE
7.10	Potency	79.4	nM	CHEMBL1562232
7.10	Potency	79.4	nM	CHEMBL1484632
7.10	Potency	79.4	nM	CHEMBL3189242
7.10	Potency	79.4	nM	CHEMBL1453996
7.10	Potency	79.4	nM	CHEMBL1595632
7.10	Potency	79.4	nM	CHEMBL1502133
7.10	Potency	79.4	nM	CHEMBL1521172
7.10	Potency	79.4	nM	CHEMBL1559529

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	increases expression	1
nickel chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	affects binding	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	increases expression	1
Zoledronic Acid	increases expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Diethylhexyl Phthalate	decreases expression, increases expression	1
Diethylstilbestrol	increases expression	1
Homocysteine	affects expression, affects cotreatment	1
Ivermectin	decreases expression	1
Ketoconazole	increases expression	1
Methionine	affects cotreatment, affects expression	1
Phenobarbital	affects expression	1

ChEMBL screening assays

7 unique, capped per target: 7 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613838	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Rab9 Promoter Activators. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2D6	Abcam HeLa RAB9A KO	Cancer cell line	Female
CVCL_TI30	HAP1 RAB9A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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