RAB27B

Summary

RAB27B (RAB27B, member RAS oncogene family, HGNC:9767) is a protein-coding gene on chromosome 18q21.2, encoding Ras-related protein Rab-27B (O00194). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Enables guanyl ribonucleotide binding activity; myosin V binding activity; and protein domain specific binding activity. Involved in multivesicular body sorting pathway and positive regulation of exocytosis. Located in Golgi stack and cytoplasmic vesicle.

Source: NCBI Gene 5874 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 31 total — 1 pathogenic
• MANE Select transcript: NM_004163

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9767
Approved symbol	RAB27B
Name	RAB27B, member RAS oncogene family
Location	18q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000041353
Ensembl biotype	protein_coding
OMIM	603869
Entrez	5874

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000262094, ENST00000586570, ENST00000586594, ENST00000592334, ENST00000895850, ENST00000962461, ENST00000962462, ENST00000962463

RefSeq mRNA: 2 — MANE Select: NM_004163 NM_001375327, NM_004163

CCDS: CCDS11958

Canonical transcript exons

ENST00000262094 — 6 exons

Exon	Start	End
ENSE00000335186	54884333	54884436
ENSE00001103711	54889224	54895516
ENSE00001103716	54887995	54888118
ENSE00002917077	54828477	54828700
ENSE00003474279	54879369	54879454
ENSE00003475328	54877567	54877738

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.2066 / max 1420.1051, expressed in 1225 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170314	13.5528	1065
170305	2.9121	372
170316	0.9931	203
170313	0.3368	146
170315	0.2187	83
170306	0.1815	81
170312	0.0116	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	98.65	gold quality
gingival epithelium	UBERON:0001949	98.37	gold quality
gingiva	UBERON:0001828	98.21	gold quality
endothelial cell	CL:0000115	98.17	gold quality
upper leg skin	UBERON:0004262	97.85	gold quality
oral cavity	UBERON:0000167	97.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.13	gold quality
middle temporal gyrus	UBERON:0002771	96.92	gold quality
skin of hip	UBERON:0001554	96.53	gold quality
germinal epithelium of ovary	UBERON:0001304	96.27	gold quality
mammalian vulva	UBERON:0000997	95.99	gold quality
parotid gland	UBERON:0001831	95.48	gold quality
mammary duct	UBERON:0001765	94.90	gold quality
epithelium of nasopharynx	UBERON:0001951	94.50	gold quality
pharyngeal mucosa	UBERON:0000355	94.39	gold quality
entorhinal cortex	UBERON:0002728	94.16	gold quality
amniotic fluid	UBERON:0000173	93.30	gold quality
pylorus	UBERON:0001166	92.74	gold quality
penis	UBERON:0000989	92.51	gold quality
palpebral conjunctiva	UBERON:0001812	92.37	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.00	gold quality
epithelium of esophagus	UBERON:0001976	91.53	gold quality
superior frontal gyrus	UBERON:0002661	91.10	gold quality
sperm	CL:0000019	90.96	gold quality
visceral pleura	UBERON:0002401	90.94	gold quality
substantia nigra pars compacta	UBERON:0001965	90.70	gold quality
colonic mucosa	UBERON:0000317	90.41	gold quality
epithelium of mammary gland	UBERON:0003244	90.40	gold quality
parietal lobe	UBERON:0001872	90.09	gold quality
postcentral gyrus	UBERON:0002581	90.07	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	38.26
E-CURD-122	yes	21.25
E-HCAD-10	yes	16.63
E-ANND-3	yes	9.16
E-GEOD-130148	yes	7.84
E-GEOD-135922	yes	7.37
E-MTAB-5061	no	3.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RAB27A

miRNA regulators (miRDB)

304 targeting RAB27B, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
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-9-5P	100.00	72.28	2361
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084

Literature-anchored findings (GeneRIF, showing 38)

• Chromosomal mapping and gene structure of the RAB27B gene. (PMID:11178108)
• Rab27b is functionally redundant with Rab27a and the pathogenesis of Griscelli syndrome is determined by the relative expression of Rab27a and Rab27b in specialized cell types. (PMID:12122117)
• During primate spermiogenesis, dynein, myosin Va, MyRIP and Rab27b that compose microtubule-based and actin-based vesicle transport systems are actually present in the manchette and might possibly be involved in intramanchette transport. (PMID:18478159)
• Rab27B regulates invasive growth and metastasis in ER-positive breast cancer cell lines, and increased expression is associated with poor prognosis in humans. (PMID:20484105)
• Rab27b is associated with tubulovesicle membranes in the parietal cell and Rab27b may play a role in stimulation-associated membrane recruitment and gastric acid secretion. (PMID:20888820)
• were unable to find any mutation in the coding sequence of RAB27B in five patients suffering from different types of platelet delta-storage pool deficiency (PMID:21198862)
• in human breast cancer specimens, the presence of Rab27B protein proved to be associated with a low degree of differentiation and the presence of lymph node metastasis in ER-positive breast cancer (PMID:21304180)
• These results suggest that Rab27b negatively regulates the cell surface expression of c-kit via secretion of SCF and that ligation of SCF leads to the endolysosomal degradation system of c-kit. (PMID:22349512)
• findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype (PMID:23217148)
• inhibiting V-ATPase activity by interfering agents and drugs might be an effective strategy for blocking Rab27B-dependent proinvasive secretory vesicle trafficking in ERalpha-positive breast cancer patients (PMID:23390068)
• Experimental data are reviewed with a focus on the secretory Rab27 family of small GTPases and their implications in cancer progression. (PMID:23665896)
• Silencing of the exocytotic RAB family members RAB27A or RAB27B halted miR23b and miR921 secretion and reduced cellular invasion. (PMID:25261234)
• Rab27B nuclear expression is correlated with several clinicopathological features of GIST patients, and it may serve as an unfavorable prognostic marker. (PMID:25382899)
• Decreased invasion partly resulted from reduced expression and activation of MMP-9 after Rab27b knockdown. Downregulation of Rab27b also suppressed tumor growth in vivo. (PMID:26165699)
• Data indicate that the secretion of microRNA miR-143, depends on rab GTP-binding proteins Rab7a and Rab27b. (PMID:26348397)
• Data indicate that a significant correlation between rab GTP-binding protein (RAB27B) and p53 tumor suppressor protein (p53) expression was observed. (PMID:26418905)
• decreased expression of Rab27A and Rab27B, especially Rab27A, closely correlated with tumor progression and are valuable prognostic indicators in colorectal cancer patients. (PMID:26760980)
• These data indicate that Rab27B is involved at a different steps of zymogen granule maturation and secretion, which is distinct from that of Rab3D. (PMID:26845357)
• MiR-193a-3p and miR-193a-5p play important roles in osteosarcoma metastasis through down-regulation of the Rab27B and SRR genes and therefore may serve as useful biomarkers for the diagnosis of osteosarcoma (PMID:26913720)
• RAB27A, RAB27B and VPS36 are frequently underexpressed in advanced prostate cancer and are inversely correlated with prostate cancer outcome. There seems to be a close relationship in the expression of RAB27A, RAB27B and VPS36, with RAB27A and RAB27B being dependent on VPS36. (PMID:28197629)
• Findings indicate that rab GTP-binding proteins Rab27A and Rab27B play significant roles in cell invasion, proliferation, and apoptosis, as well as in chemotherapy resistance. (PMID:28902788)
• High Rab27B expression could be an unfavorable prognostic factor in patients with squamous cell carcinoma of the lung (PMID:30480360)
• Results indicate that Rab27b is highly expressed in lung adenocarcinoma (LUAD) and correlates with malignant attributes of LUAD suggesting that Rab27b may be identified as a potential indicator of metastasis and prognosis for LUAD. (PMID:30627227)
• Data show that member RAS oncogene family protein RAB27B (RAB27B) expression is required for the secretion of colorectal cancer stem cells (CRCSCs) exosomes, and exosomal miR-146a promotes stem-like properties and tumorigenicity by targeting endocytic adaptor protein Numb (Numb) in colorectal cancer (CRC) cells. (PMID:30980673)
• The GTPase Rab27b regulates the release, autophagic clearance, and toxicity of alpha-synuclein. (PMID:32350025)
• oncogenic effects through exosome independent function in renal cell carcinoma including sunitinib-resistant (PMID:32379831)
• Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux. (PMID:32390047)
• A hypoxia-induced Rab pathway regulates embryo implantation by controlled trafficking of secretory granules. (PMID:32513733)
• Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth. (PMID:32784729)
• Abnormal expression of Rab27B in prostatic epithelial cells of benign prostatic hyperplasia alters intercellular communication. (PMID:33285290)
• Human multipotent mesenchymal stromal cells cytokine priming promotes RAB27B-regulated secretion of small extracellular vesicles with immunomodulatory cargo. (PMID:33317598)
• NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression. (PMID:34686330)
• RAB27A and RAB27B Expression May Predict Lymph Node Metastasis and Survival in Patients With Gastric Cancer. (PMID:35985682)
• Rab27b, a Regulator of Exosome Secretion, Is Associated With Peritoneal Metastases in Gastric Cancer. (PMID:36581340)
• RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion. (PMID:37077938)
• RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia. (PMID:37317963)
• Rab27b promotes endometriosis by enhancing invasiveness of ESCs and promoting angiogenesis. (PMID:37641372)
• RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment. (PMID:38036630)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab27b	ENSDARG00000087762
mus_musculus	Rab27b	ENSMUSG00000024511
rattus_norvegicus	Rab27b	ENSRNOG00000012176

Paralogs (68): RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955), RAB41 (ENSG00000147127)

Protein

Protein identifiers

Ras-related protein Rab-27B — O00194 (reviewed: O00194)

Alternative names: C25KG

All UniProt accessions (3): O00194, K7EJ38, K7ES41

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. RAB27B regulates homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion. Plays a role in NTRK2/TRKB axonal anterograde transport by facilitating the association of NTRK2/TRKB with KLC1. May be involved in targeting uroplakins to urothelial apical membranes.

Subunit / interactions. Interacts with SYTL2, SYTL4, MYRIP and MLPH. Interacts with RPH3A and RPH3A. Interacts (GDP-bound form preferentially) with DENND10.

Subcellular location. Membrane. Late endosome.

Tissue specificity. Expressed primarily in testis.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) including DENND10, 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.

RefSeq proteins (2): NP_001362256, NP_004154* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041837	Rab27a/b	Family
IPR050305	Small_GTPase_Rab	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (47 total): binding site 19, strand 6, helix 6, region of interest 3, modified residue 2, lipid moiety-binding region 2, mutagenesis site 2, turn 2, initiator methionine 1, chain 1, disulfide bond 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2F7S	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00194-F1	85.41	0.61

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 (19): 22; 23; 23; 24; 36; 40; 41; 41; 74; 77; 133; 136 …

Post-translational modifications (4): 2, 218, 216, 218

Disulfide bonds (1): 123–188

Mutagenesis-validated functional residues (2):

Position	Phenotype
23	gdp-locked. increases interaction with dennd10. disrupts late endocytic pathway homeostasis.
78	gtp-locked. decreases interaction with dennd10.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 323 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_EXOCYTOSIS, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, CHANDRAN_METASTASIS_DN, GOBP_SYNAPTIC_VESICLE_RECYCLING

GO Biological Process (6): exocytosis (GO:0006887), positive regulation of exocytosis (GO:0045921), synaptic vesicle endocytosis (GO:0048488), multivesicular body sorting pathway (GO:0071985), anterograde axonal protein transport (GO:0099641), regulation of exocytosis (GO:0017157)

GO Molecular Function (9): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), protein domain specific binding (GO:0019904), myosin V binding (GO:0031489), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (17): late endosome (GO:0005770), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), trans-Golgi network transport vesicle (GO:0030140), secretory granule (GO:0030141), synaptic vesicle membrane (GO:0030672), platelet dense granule membrane (GO:0031088), multivesicular body membrane (GO:0032585), melanosome (GO:0042470), zymogen granule membrane (GO:0042589), extracellular exosome (GO:0070062), exocytic vesicle (GO:0070382), axon cytoplasm (GO:1904115), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Post-translational protein modification	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
vesicle-mediated transport	2
exocytosis	2
guanyl ribonucleotide binding	2
transport vesicle	2
secretory vesicle	2
secretory granule membrane	2
secretion by cell	1
vesicle fusion to plasma membrane	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
anterograde axonal transport	1
axo-dendritic protein transport	1
protein localization to presynapse	1
regulation of vesicle-mediated transport	1
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
myosin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
endosome	1
cytoplasm	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
Golgi-associated vesicle	1
clathrin-coated vesicle	1
synaptic vesicle	1

Protein interactions and networks

STRING

1002 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB27B	MYRIP	Q8NFW9	957
RAB27B	MLPH	Q9BV36	941
RAB27B	UNC13D	Q70J99	895
RAB27B	MYO5A	Q9Y4I1	882
RAB27B	SYTL1	Q8IYJ3	854
RAB27B	EXPH5	Q8NEV8	812
RAB27B	CD63	P08962	773
RAB27B	SYTL4	Q96C24	757
RAB27B	DPYSL2	Q16555	753
RAB27B	RPH3A	Q9Y2J0	726
RAB27B	SYTL2	Q9HCH5	720
RAB27B	MREG	Q8N565	690
RAB27B	TSG101	Q99816	649
RAB27B	B4E171	B4E171	624
RAB27B	TBC1D10A	Q9BXI6	614

IntAct

43 interactions, top by confidence:

A	B	Type	Score
SYTL5	RAB27B	psi-mi:“MI:0915”(physical association)	0.850
RAB27B	SYTL5	psi-mi:“MI:0915”(physical association)	0.850
SYTL5	RAB27B	psi-mi:“MI:0914”(association)	0.850
RAB27B	MLPH	psi-mi:“MI:0915”(physical association)	0.740
RAB27B	DHPS	psi-mi:“MI:0915”(physical association)	0.720
DHPS	RAB27B	psi-mi:“MI:0915”(physical association)	0.720
SYTL5	RAB27B	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	MYRIP	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	RPH3A	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	GORASP2	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	SYTL5	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	RPH3AL	psi-mi:“MI:0915”(physical association)	0.560
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.530
RAB27B	CAV1	psi-mi:“MI:0915”(physical association)	0.520
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
RAB27A	GTPBP1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
NRM	RAB27B	psi-mi:“MI:0914”(association)	0.350
RAB27B	MYH7B	psi-mi:“MI:0914”(association)	0.350
SLC22A2	RAB27B	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): RAB27B (Two-hybrid), SYTL5 (Two-hybrid), SYTL1 (Affinity Capture-MS), SYTL2 (Affinity Capture-MS), SYTL4 (Affinity Capture-MS), SYTL5 (Affinity Capture-MS), CCDC186 (Affinity Capture-MS), SYTL3 (Affinity Capture-MS), CHM (Affinity Capture-MS), BDH2 (Affinity Capture-MS), GBA (Affinity Capture-MS), SCARB2 (Affinity Capture-MS), CHML (Affinity Capture-MS), RAB27B (Affinity Capture-MS), RAB27B (Proximity Label-MS)

ESM2 similar proteins: A6QR46, C4YL11, O00194, O18334, O23657, O49841, O80501, P0CY30, P0CY31, P10949, P17608, P20340, P34213, P35279, P35289, P35293, P36017, P55745, P59190, P61294, P62823, P62824, P90726, Q05976, Q0IIG8, Q17R06, Q1KME6, Q1RMR4, Q22782, Q54DA7, Q55FK2, Q5R5H5, Q5RAV6, Q5ZLG1, Q6DHC1, Q8CG50, Q8HZJ5, Q8K386, Q8MXS1, Q96E17

Diamond homologs: A4FV54, C4YL11, F1PTE3, O00194, O24466, O42819, O95716, P07560, P0CY30, P0CY31, P10536, P10948, P10949, P11023, P17609, P20336, P20337, P20790, P20791, P22125, P22127, P22128, P23640, P24409, P25228, P28186, P28188, P31584, P33723, P34139, P34140, P35276, P35280, P35286, P36861, P40392, P41924, P51153, P51159, P55258

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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.

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein transport	5	17.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564568	GRCh37/hg19 18q12.2-21.31(chr18:35866313-55082983)x3	Pathogenic

SpliceAI

1453 predictions. Top by Δscore:

Variant	Effect	Δscore
18:54877563:A:AG	acceptor_gain	1.0000
18:54877564:C:G	acceptor_gain	1.0000
18:54877565:A:AG	acceptor_gain	1.0000
18:54877566:G:GA	acceptor_gain	1.0000
18:54877566:GACC:G	acceptor_gain	1.0000
18:54877734:GTGTG:G	donor_gain	1.0000
18:54877736:GTG:G	donor_gain	1.0000
18:54879365:TCA:T	acceptor_loss	1.0000
18:54879366:CA:C	acceptor_loss	1.0000
18:54879367:A:AG	acceptor_gain	1.0000
18:54879367:A:AT	acceptor_loss	1.0000
18:54879368:G:GG	acceptor_gain	1.0000
18:54879368:GGTTT:G	acceptor_gain	1.0000
18:54879450:GAGCG:G	donor_gain	1.0000
18:54879452:GCG:G	donor_gain	1.0000
18:54879455:G:GG	donor_gain	1.0000
18:54879461:G:GG	donor_gain	1.0000
18:54884435:GA:G	donor_gain	1.0000
18:54884437:G:GG	donor_gain	1.0000
18:54887992:A:AG	acceptor_gain	1.0000
18:54887993:A:AG	acceptor_gain	1.0000
18:54887994:G:GG	acceptor_gain	1.0000
18:54828547:GAGA:G	donor_gain	0.9900
18:54859370:T:G	donor_gain	0.9900
18:54877561:A:AG	acceptor_gain	0.9900
18:54877562:T:G	acceptor_gain	0.9900
18:54877562:TACAG:T	acceptor_loss	0.9900
18:54877565:A:AT	acceptor_loss	0.9900
18:54877565:AGACC:A	acceptor_gain	0.9900
18:54877566:G:GT	acceptor_loss	0.9900

AlphaMissense

1440 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:54877653:C:T	T23I	1.000
18:54877707:C:T	T41I	1.000
18:54877712:G:A	G43R	1.000
18:54877712:G:C	G43R	1.000
18:54877713:G:A	G43E	1.000
18:54879432:T:A	W73R	1.000
18:54879432:T:C	W73R	1.000
18:54879435:G:C	D74H	1.000
18:54879436:A:C	D74A	1.000
18:54879436:A:T	D74V	1.000
18:54879445:G:A	G77E	1.000
18:54884334:T:C	F81L	1.000
18:54884336:C:A	F81L	1.000
18:54884336:C:G	F81L	1.000
18:54888053:G:C	K134N	1.000
18:54888053:G:T	K134N	1.000
18:54877631:G:A	G16R	0.999
18:54877631:G:C	G16R	0.999
18:54877631:G:T	G16W	0.999
18:54877632:G:A	G16E	0.999
18:54877632:G:T	G16V	0.999
18:54877646:G:A	G21R	0.999
18:54877646:G:C	G21R	0.999
18:54877646:G:T	G21W	0.999
18:54877647:G:A	G21E	0.999
18:54877649:A:C	K22Q	0.999
18:54877650:A:T	K22M	0.999
18:54877651:G:C	K22N	0.999
18:54877651:G:T	K22N	0.999
18:54877685:T:C	F34L	0.999

dbSNP variants (sampled 300 via entrez): RS1000006013 (18:54799690 C>T), RS1000045432 (18:54888325 T>G), RS1000059189 (18:54888300 C>T), RS1000070547 (18:54825317 G>A), RS1000071527 (18:54759123 G>A,T), RS1000082116 (18:54739521 A>C,G), RS1000117813 (18:54810250 G>A,T), RS1000119524 (18:54834742 C>A,G), RS1000127443 (18:54839526 T>G), RS1000131290 (18:54895180 T>A), RS1000149989 (18:54724237 G>C), RS1000150095 (18:54760331 A>G), RS1000154125 (18:54763157 AAT>A), RS1000164637 (18:54793857 G>A), RS1000178629 (18:54754508 G>A,T)

Disease associations

OMIM: gene MIM:603869 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003177_38	Childhood body mass index	8.000000e-09
GCST004751_21	Serum uric acid levels in response to allopurinol in gout	2.000000e-06
GCST004751_8	Serum uric acid levels in response to allopurinol in gout	1.000000e-06
GCST004904_198	Body mass index	8.000000e-10
GCST005038_51	Allergic disease (asthma, hay fever or eczema)	6.000000e-09
GCST005839_20	Depression	3.000000e-08
GCST010988_3	Adult body size	1.000000e-13
GCST010989_283	Body size at age 10	2.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004761	uric acid measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	6
bisphenol A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
S-(1,2-dichlorovinyl)cysteine	decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Arsenic Trioxide	decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression	2
GSK-J4	increases expression	1
ginger extract	increases abundance, increases expression	1
securinine	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases expression, decreases reaction	1
butyraldehyde	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
2-palmitoylglycerol	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
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1

Clinical trials (associated diseases)

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