RAB25

Summary

RAB25 (RAB25, member RAS oncogene family, HGNC:18238) is a protein-coding gene on chromosome 1q22, encoding Ras-related protein Rab-25 (P57735). 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 is a member of the RAS superfamily of small GTPases. The encoded protein is involved in membrane trafficking and cell survival. This gene has been found to be a tumor suppressor and an oncogene, depending on the context. Two variants, one protein-coding and the other not, have been found for this gene.

Source: NCBI Gene 57111 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_020387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18238
Approved symbol	RAB25
Name	RAB25, member RAS oncogene family
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	CATX-8
Ensembl gene	ENSG00000132698
Ensembl biotype	protein_coding
OMIM	612942
Entrez	57111

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000361084, ENST00000463614, ENST00000473336, ENST00000487325, ENST00000497968, ENST00000876131, ENST00000921089, ENST00000921090

RefSeq mRNA: 1 — MANE Select: NM_020387 NM_020387

CCDS: CCDS41413

Canonical transcript exons

ENST00000361084 — 5 exons

Exon	Start	End
ENSE00000855863	156065911	156066106
ENSE00001842111	156061160	156061443
ENSE00003507895	156068270	156068463
ENSE00003510202	156069671	156069751
ENSE00003604681	156070160	156070504

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 99.42.

FANTOM5 (CAGE): breadth broad, TPM avg 27.9444 / max 477.5487, expressed in 511 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5656	25.8696	506
5657	2.0748	396

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.42	gold quality
mucosa of transverse colon	UBERON:0004991	99.00	gold quality
esophagus mucosa	UBERON:0002469	98.88	gold quality
esophagus squamous epithelium	UBERON:0006920	98.55	gold quality
skin of abdomen	UBERON:0001416	98.45	gold quality
skin of leg	UBERON:0001511	98.15	gold quality
gingiva	UBERON:0001828	98.08	gold quality
pharyngeal mucosa	UBERON:0000355	98.05	gold quality
gingival epithelium	UBERON:0001949	97.87	gold quality
epithelium of esophagus	UBERON:0001976	97.87	gold quality
upper leg skin	UBERON:0004262	97.84	gold quality
zone of skin	UBERON:0000014	97.60	gold quality
oral cavity	UBERON:0000167	97.50	gold quality
rectum	UBERON:0001052	97.23	gold quality
penis	UBERON:0000989	97.21	gold quality
mammalian vulva	UBERON:0000997	97.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.97	gold quality
palpebral conjunctiva	UBERON:0001812	96.92	gold quality
squamous epithelium	UBERON:0006914	96.36	gold quality
mouth mucosa	UBERON:0003729	96.30	gold quality
body of pancreas	UBERON:0001150	96.17	gold quality
tongue squamous epithelium	UBERON:0006919	96.02	gold quality
minor salivary gland	UBERON:0001830	95.98	gold quality
upper arm skin	UBERON:0004263	95.94	gold quality
colonic mucosa	UBERON:0000317	95.07	gold quality
ileal mucosa	UBERON:0000331	95.02	gold quality
right uterine tube	UBERON:0001302	94.76	gold quality
left lobe of thyroid gland	UBERON:0001120	94.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.72	gold quality
saliva-secreting gland	UBERON:0001044	94.71	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	264.57
E-MTAB-8205	yes	150.74
E-CURD-11	yes	95.84
E-CURD-114	yes	70.01
E-MTAB-8410	yes	51.19
E-MTAB-10287	yes	48.78
E-HCAD-10	yes	24.24
E-GEOD-125970	yes	16.07
E-MTAB-9388	yes	11.19
E-MTAB-8271	yes	8.25
E-MTAB-3929	no	233.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, GRHL2, ZEB1

miRNA regulators (miRDB)

21 targeting RAB25, 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-4673	100.00	66.64	1490
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-4761-3P	96.27	66.26	524
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-8071	95.69	64.93	484
HSA-MIR-1256	95.44	66.33	784

Literature-anchored findings (GeneRIF, showing 36)

• Rab25 signalling pathway plays a role in the regulation of cell proliferation and apoptosis in ovarian cancer cells, which indicates that the Rab25 gene plays a definite role in the development and aggressiveness of human ovarian cancer. (PMID:17393986)
• Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix. (PMID:17925226)
• Loss of Rab25 is associated with triple-negative breast cancer. (PMID:19795443)
• Rab25 may function as a tumor suppressor in intestinal epithelial cells through regulation of protein trafficking to the cell surface. (PMID:20197623)
• The present study delineates the fundamental elements of a core promoter structure that will be helpful for future studies regarding the regulation of RAB25 gene. (PMID:21075212)
• Rab25 effectively differentiates Mullerian carcinomas from malignant mesothelioma (PMID:22249560)
• Rab25 induced the accumulation of glycogen in epithelial cancer cells, a process not previously identified. (RAB25) (PMID:22253197)
• Rab25 acts predominantly in the small-scale fast recycling within the tips of the cell. Our results further support the idea of Rab25 as a promoter of tumor development (PMID:22613965)
• higher level of Rab25 was associated with lymphatic metastasis, specifically in ER and PR-positive breast cancer. (PMID:22644676)
• Studies using lentiviral-based overexpression and suppression systems lent support of Rab25 to function as an important tumor suppressor with both anti-invasive and -angiogenic abilities, through a deregulated FAK-Raf-MEK1/2-ERK signaling pathway. (PMID:22991305)
• data showed Rab25 was highly expressed in all subtypes of epithelial ovarian cancers, and two subtypes of germ cell tumors, but not in sex cord stromal tumors; Rab25 expression was not correlated with peritoneal metastasis of ovarian cancer (PMID:23030522)
• RAB25 has been implicated in various cancers, with reports presenting it as both an oncogene and a tumour-suppressor gene. [Review] (PMID:23176489)
• These findings suggest that Rab25 plays an important role in tumor migration and metastasis, and that understanding its function may lead to the development of new strategies to prevent metastasis in oral cancer patients. (PMID:23340300)
• Rab25 controls intestinal cell polarity through the regulation of gene expression (PMID:23345591)
• Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3beta/Snail signaling. (PMID:23722651)
• the crystal structure of Rab25 in complex with the C-terminal region of FIP2, which consists of a central dimeric FIP2 coiled-coil that mediates a heterotetrameric Rab25-(FIP2)2-Rab25 complex. (PMID:24056041)
• High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma. (PMID:24403269)
• These results showed that high levels of Rab25 expression were significantly correlated with renal cell carcinoma invasion classification (P < 0.01), lymph-node metastasis (P < 0.001), and pathological stage (P < 0.01). (PMID:25686498)
• Rab25 expression is a potential prognostic index for advanced NSCLC patients and its inhibition may improve chemosensitization in NSCLC treatment. (PMID:26535714)
• Data show that both rab G-Protein RAB25 and RNA-binding protein ESRP1 were suppressed by transcription factor ZEB1, which was in turn regulated via epigenetic mechanisms. (PMID:26646320)
• Rab25 was upregulated in hepatocellular carcinoma tissues and cells compared with normal liver tissues and cell lines. Rab25 overexpression correlated with advanced tumor stage and nodal metastasis.Rab25 depletion blocked cell growth rate, inhibited colony formation, downregulated AKT phosphorylation, inhibited the Wnt signaling pathway and its target genes, and negatively regulated the invading ability of HCC cells. (PMID:26692100)
• Our results suggest that Rab25 tumourigenic potential and chemoresistance relies on HIF1 activity in aggressive and metastatic ovarian cancer (PMID:26967059)
• Rab25 is amplified and enhances aggressiveness in luminal B cancers while in claudin-low tumors, Rab25 is lost indicating possible anti-tumor functions (PMID:27259233)
• Promoter methylation results in downregulation of RAB25 expression in oropharyngeal squamous cell carcinoma. Decreased Rsb25 expression is associated with lymph node metastasis. (PMID:27379752)
• Rab25 may act as a tumor promoter. (PMID:28281975)
• Data show that Rab25 is responsible for RIN1-induced EGFR signaling and tumor malignancy in clear cell renal cell carcinoma cell. (PMID:28612496)
• The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. (PMID:28922401)
• Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma (PMID:29079774)
• Rab25 modulates cancer cell invasion through coordinated regulation of beta1-integrin to activation of EGFR and expression of VEGF-A to increase the level of Snail protein and subsequent Fascin expression. (PMID:29371698)
• Results indicated that miR-577 suppressed EMT by inhibiting Rab25 expression in breast cancer (BC). MiR-577 and Rab25 are considered potential targets of BC treatment. (PMID:29524309)
• ZEB2 directly binds to E-box sequences in the RAB25 promoter.ZEB2 stably represses RAB25 expression through epigenetic regulation by SIRT1 during epithelial-to-mesenchymal transition. (PMID:30445998)
• Rab25 overexpression induced erlotinib resistance, whereas Rab25 knockdown reversed this refractoriness in vitro and in vivo. Moreover, Rab25 interacts with beta1 integrin and promotes its trafficking to the cytoplasmic membrane. (PMID:30848009)
• Loss of Rab25 promotes the development and neoplastic transition of skin squamous cell carcinoma through dysregulation of integrin trafficking. (PMID:31144312)
• Long non-coding RNA LINC00173 serves as sponge for miR-338-3p to promote prostate cancer progression via regulating Rab25. (PMID:33015770)
• Expression of Rab25 is down-regulated in the foreskin of children with hypospadias. (PMID:37246119)
• Loss of RAB25 Cooperates with Oncogenes in the Transformation of Human Mammary Epithelial Cells (HMECs) to Give Rise to Claudin-Low Tumors. (PMID:38803515)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab25b	ENSDARG00000052954
danio_rerio	rab25a	ENSDARG00000058800
mus_musculus	Rab25	ENSMUSG00000008601
rattus_norvegicus	Rab25	ENSRNOG00000023640

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), 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-25 — P57735 (reviewed: P57735)

Alternative names: CATX-8

All UniProt accessions (1): P57735

UniProt curated annotations — full annotation on UniProt →

Function. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB25 regulates epithelial cell differentiation, proliferation and survival, thereby playing key roles in tumorigenesis. Promotes invasive migration of cells in which it functions to localize and maintain integrin alpha-V/beta-1 at the tips of extending pseudopodia. Involved in the regulation of epithelial morphogenesis through the control of CLDN4 expression and localization at tight junctions. May selectively regulate the apical recycling pathway. Together with MYO5B regulates transcytosis.

Subunit / interactions. Interacts (GTP-bound form) with RAB11FIP1, RAB11FIP2, RAB11FIP3 and RAB11FIP4. Interacts (via the hypervariable C-terminal region) with ITGB1 (via the cytoplasmic region); the interaction is GTP-dependent. Interacts with ITGAV. Associates with the integrin alpha-V/beta-1 heterodimer. Interacts with VPS33B.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Cell projection. Pseudopodium membrane.

Tissue specificity. Expression is restricted to epithelial cells. Expressed in ovarian epithelium (NOE) and breast tissue. Expressed in ovarian cancer; expression is increased relative to NOE cells. Expression in ovarian cancer is stage dependent, with stage III and stage IV showing higher levels than early stage cancers. Expressed in breast cancer; expression is increased relative to normal breast tissue.

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) which prevent Rab-GDP dissociation.

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 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.

RefSeq proteins (1): NP_065120* (*=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

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (40 total): binding site 18, helix 7, strand 6, short sequence motif 2, lipid moiety-binding region 2, chain 1, propeptide 1, modified residue 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3TSO	X-RAY DIFFRACTION	1.8
2OIL	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57735-F1	87.54	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 (18): 38; 39; 43; 44; 44; 67; 70; 125; 126; 128; 156; 157 …

Post-translational modifications (3): 210, 209, 210

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 148 (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, ATF_B, GOBP_EPITHELIUM_DEVELOPMENT, GAANYNYGACNY_UNKNOWN, GOBP_EPITHELIAL_CELL_DEVELOPMENT, JAEGER_METASTASIS_DN, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GGGTGGRR_PAX4_03, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, RODRIGUES_NTN1_TARGETS_DN, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, CREB_Q4

GO Biological Process (7): epithelial cell morphogenesis (GO:0003382), exocytosis (GO:0006887), positive regulation of cell population proliferation (GO:0008284), positive regulation of epithelial cell migration (GO:0010634), protein transport (GO:0015031), pseudopodium organization (GO:0031268), regulation of vesicle-mediated transport (GO:0060627)

GO Molecular Function (7): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), myosin V binding (GO:0031489), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), pseudopodium (GO:0031143), pseudopodium membrane (GO:0031260), cytoplasmic vesicle (GO:0031410), recycling endosome (GO:0055037), extracellular exosome (GO:0070062), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle-mediated transport	2
cytoplasm	2
cellular anatomical structure	2
cell morphogenesis	1
epithelial cell development	1
secretion by cell	1
vesicle fusion to plasma membrane	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
plasma membrane bounded cell projection organization	1
regulation of cellular process	1
regulation of transport	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
myosin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
pseudopodium	1
cell projection membrane	1
intracellular vesicle	1
endosome	1
extracellular vesicle	1

Protein interactions and networks

STRING

2829 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB25	RAB11FIP1	Q6WKZ4	974
RAB25	RAB11FIP2	Q7L804	948
RAB25	MYO5B	Q9ULV0	931
RAB25	RAB11FIP5	Q9BXF6	917
RAB25	RAB11FIP3	O75154	857
RAB25	RAB11FIP4	Q86YS3	833
RAB25	EXOC7	Q9UPT5	652
RAB25	ITGA5	P08648	650
RAB25	ARF6	P26438	615
RAB25	CLIC3	O95833	582
RAB25	ARF5	P26437	545
RAB25	OPTN	Q96CV9	537
RAB25	SNAI1	O95863	498
RAB25	RDX	P35241	490
RAB25	CHML	P26374	475

IntAct

55 interactions, top by confidence:

A	B	Type	Score
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
RAB25	RAB11FIP2	psi-mi:“MI:0915”(physical association)	0.560
RAB25	MYO5B	psi-mi:“MI:0915”(physical association)	0.560
RAB25	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
RAB25	BRAF	psi-mi:“MI:0915”(physical association)	0.550
RAB25	BRAF	psi-mi:“MI:2364”(proximity)	0.550
BRAF	RAB25	psi-mi:“MI:0915”(physical association)	0.550
RAB11A	SH3BP5	psi-mi:“MI:0914”(association)	0.530
HUS1B	RAD1	psi-mi:“MI:0914”(association)	0.530
	RAB25	psi-mi:“MI:0915”(physical association)	0.520
RAB25		psi-mi:“MI:0915”(physical association)	0.520
PDE4DIP	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (280): RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-RNA), RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), AP2S1 (Affinity Capture-MS), RAB25 (Affinity Capture-Western), RAB25 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), RAB25 (Proximity Label-MS), RAB25 (Two-hybrid)

ESM2 similar proteins: E2RQ15, O01803, O23561, P05714, P10948, P19892, P20337, P20338, P25766, P28185, P28187, P31583, P36412, P46629, P51146, P56371, P57735, P61017, P61018, P61020, Q0WQN4, Q2TBH7, Q32NQ0, Q3ZC27, Q40191, Q40520, Q40522, Q40523, Q40723, Q53B90, Q58DW6, Q5KTJ7, Q5RBG1, Q63941, Q63942, Q68EK7, Q6PHI9, Q86YS6, Q8CG50, Q91ZR1

Diamond homologs: A5D7F5, A8HN58, E2RQ15, M0RC99, O01803, O04486, O14966, O35509, O35963, O49513, O80501, P01123, P17608, P18066, P19892, P20339, P22129, P25766, P28185, P29687, P31583, P34143, P35278, P36862, P40393, P46629, P46638, P51146, P51147, P51148, P57735, P61017, P61018, P61020, P61021, P61271, P62490, P62491, P62492, P62493

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

579 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156065909:A:AG	acceptor_gain	1.0000
1:156065909:AGT:A	acceptor_gain	1.0000
1:156065910:G:GC	acceptor_gain	1.0000
1:156065910:GT:G	acceptor_gain	1.0000
1:156065910:GTG:G	acceptor_gain	1.0000
1:156066105:GC:G	donor_gain	1.0000
1:156068258:A:AG	acceptor_gain	1.0000
1:156068259:T:G	acceptor_gain	1.0000
1:156068264:A:AG	acceptor_gain	1.0000
1:156068265:C:G	acceptor_gain	1.0000
1:156068265:CCCA:C	acceptor_loss	1.0000
1:156068268:A:AG	acceptor_gain	1.0000
1:156068268:AG:A	acceptor_gain	1.0000
1:156068269:G:A	acceptor_loss	1.0000
1:156068269:G:GA	acceptor_gain	1.0000
1:156068269:GG:G	acceptor_gain	1.0000
1:156068269:GGT:G	acceptor_gain	1.0000
1:156068269:GGTA:G	acceptor_gain	1.0000
1:156068269:GGTAC:G	acceptor_gain	1.0000
1:156068430:G:GT	donor_gain	1.0000
1:156068430:G:T	donor_gain	1.0000
1:156068445:G:GT	donor_gain	1.0000
1:156068460:GCTG:G	donor_gain	1.0000
1:156068461:CTGG:C	donor_loss	1.0000
1:156068463:GGTGA:G	donor_loss	1.0000
1:156068464:G:C	donor_loss	1.0000
1:156068464:G:GG	donor_gain	1.0000
1:156068465:T:A	donor_loss	1.0000
1:156069665:T:TA	acceptor_gain	1.0000
1:156069666:G:A	acceptor_gain	1.0000

AlphaMissense

1374 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156065944:C:T	T26I	1.000
1:156066012:T:C	F49L	1.000
1:156066014:C:A	F49L	1.000
1:156066014:C:G	F49L	1.000
1:156066063:T:A	W66R	1.000
1:156066063:T:C	W66R	1.000
1:156066067:A:C	D67A	1.000
1:156066067:A:T	D67V	1.000
1:156068407:A:T	K126I	1.000
1:156068408:A:C	K126N	1.000
1:156068408:A:T	K126N	1.000
1:156065923:G:T	G19V	0.999
1:156065938:G:A	G24E	0.999
1:156065940:A:C	K25Q	0.999
1:156065941:A:T	K25M	0.999
1:156065942:G:C	K25N	0.999
1:156065942:G:T	K25N	0.999
1:156065959:G:C	R31P	0.999
1:156065976:T:C	F37L	0.999
1:156065978:C:A	F37L	0.999
1:156065978:C:G	F37L	0.999
1:156066003:G:A	G46R	0.999
1:156066003:G:C	G46R	0.999
1:156066004:G:A	G46E	0.999
1:156066013:T:C	F49S	0.999
1:156066065:G:C	W66C	0.999
1:156066065:G:T	W66C	0.999
1:156066066:G:C	D67H	0.999
1:156066067:A:G	D67G	0.999
1:156066068:C:A	D67E	0.999

dbSNP variants (sampled 300 via entrez): RS1000194146 (1:156065920 T>C), RS1000194662 (1:156066252 G>C,T), RS1000225706 (1:156066657 G>A), RS1000635740 (1:156059162 G>A,C), RS1001200511 (1:156064923 A>C), RS1001236039 (1:156065318 C>T), RS1001625444 (1:156066598 A>G), RS1002010925 (1:156070942 T>TA), RS1002092114 (1:156060253 A>G), RS1002567599 (1:156059940 T>A), RS1003017100 (1:156069454 C>G), RS1003241959 (1:156061984 C>G), RS1003271765 (1:156068731 T>C,G), RS1003302689 (1:156068202 G>A,C,T), RS1003997520 (1:156066908 C>T)

Disease associations

OMIM: gene MIM:612942 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010241_324	Apolipoprotein A1 levels	2.000000e-08
GCST010242_124	HDL cholesterol levels	2.000000e-08
GCST010991_2	Parkinson’s disease	4.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	7
trichostatin A	affects cotreatment, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
methylmercuric chloride	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium arsenite	increases expression	1
cupric chloride	decreases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	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	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases response to substance	1
Glyphosate	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	increases expression, affects cotreatment, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Mustard Gas	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Rotenone	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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