RAB7B

Summary

RAB7B (RAB7B, member RAS oncogene family, HGNC:30513) is a protein-coding gene on chromosome 1q32.1, encoding Ras-related protein Rab-7b (Q96AH8). Controls vesicular trafficking from endosomes to the trans-Golgi network (TGN).

Predicted to enable GTP binding activity and GTPase activity. Involved in late endosome to Golgi transport; positive regulation of megakaryocyte differentiation; and regulation of gene expression. Located in cytoplasmic vesicle; lysosome; and trans-Golgi network.

Source: NCBI Gene 338382 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001164522

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30513
Approved symbol	RAB7B
Name	RAB7B, member RAS oncogene family
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC9726, MGC16212
Ensembl gene	ENSG00000276600
Ensembl biotype	protein_coding
Entrez	338382

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000617070, ENST00000617991, ENST00000622969, ENST00000623597, ENST00000623893, ENST00000867182, ENST00000867183, ENST00000948130

RefSeq mRNA: 3 — MANE Select: NM_001164522 NM_001164522, NM_001304839, NM_177403

CCDS: CCDS73011, CCDS76258

Canonical transcript exons

ENST00000617070 — 6 exons

Exon	Start	End
ENSE00003727377	205985540	205985665
ENSE00003736495	205994083	205994151
ENSE00003739744	205993420	205993546
ENSE00003752220	205992480	205992695
ENSE00003755330	205976740	205978928
ENSE00003758196	206003253	206003395

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 90.66.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0695 / max 251.6558, expressed in 844 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201908	1.9106	301
201909	1.2938	477
201907	0.9589	163
201910	0.7872	470
201904	0.0553	25
201906	0.0362	15
201911	0.0275	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	90.66	gold quality
skin of abdomen	UBERON:0001416	87.98	gold quality
gingival epithelium	UBERON:0001949	87.64	gold quality
gingiva	UBERON:0001828	86.68	gold quality
zone of skin	UBERON:0000014	86.25	gold quality
skin of leg	UBERON:0001511	86.23	gold quality
upper leg skin	UBERON:0004262	85.79	gold quality
esophagus mucosa	UBERON:0002469	85.46	gold quality
gall bladder	UBERON:0002110	84.89	gold quality
lower esophagus mucosa	UBERON:0035834	83.84	gold quality
skin of hip	UBERON:0001554	83.00	gold quality
epithelial cell of pancreas	CL:0000083	81.51	gold quality
right coronary artery	UBERON:0001625	81.12	gold quality
vagina	UBERON:0000996	80.94	gold quality
mammalian vulva	UBERON:0000997	80.79	gold quality
smooth muscle tissue	UBERON:0001135	78.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.59	gold quality
penis	UBERON:0000989	78.10	gold quality
pancreatic ductal cell	CL:0002079	77.17	silver quality
parietal pleura	UBERON:0002400	76.84	gold quality
left uterine tube	UBERON:0001303	76.72	gold quality
descending thoracic aorta	UBERON:0002345	76.54	gold quality
omental fat pad	UBERON:0010414	76.45	gold quality
peritoneum	UBERON:0002358	76.36	gold quality
left lobe of thyroid gland	UBERON:0001120	76.05	gold quality
spinal cord	UBERON:0002240	75.80	gold quality
left coronary artery	UBERON:0001626	75.79	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.75	gold quality
amniotic fluid	UBERON:0000173	75.63	gold quality
ectocervix	UBERON:0012249	75.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	10.55
E-CURD-112	yes	10.21
E-MTAB-6678	yes	8.63
E-ANND-3	yes	5.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting RAB7B, 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-3120-5P	100.00	65.56	965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-7157-3P	98.95	68.70	1582

Literature-anchored findings (GeneRIF, showing 10)

• Rab7b is required for normal lysosome function, and, in particular, it is an essential factor for retrograde transport from endosomes to the trans-Golgi network. (PMID:20375062)
• Rab7b may play important roles in megakaryopoiesis by activating NF-kappaB and promoting IL-6 production. (PMID:20953574)
• Rab7b is required for sortilin transport from endosomes to the TGN. (PMID:22708738)
• 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)
• Authors determined the effects of T. suis soluble products (SPs) on Toll-like receptor-4 (TLR4)- In addition, T. suis SPs induce Rab7b, a negative regulator of TLR4 signalling (PMID:25996526)
• study demonstrates that Rab7b regulates LC3 processing by modulating Atg4B activity; taken together, findings reveal Rab7b as a novel negative regulator of autophagy through its interaction with Atg4B (PMID:28835545)
• TBC1D5 is a GAP for Rab7b in the control of endosomal transport to the trans-Golgi. (PMID:30111580)
• Rab7b participation on the TLR4 (Toll-like receptor) endocytic pathway in Shiga toxin-associated Hemolytic Uremic Syndrome (HUS). (PMID:31153054)
• Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton. (PMID:34494097)
• Listeria InlB Expedites Vacuole Escape and Intracellular Proliferation by Promoting Rab7 Recruitment via Vps34. (PMID:36656016)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rab7b	ENSMUSG00000052688
rattus_norvegicus	Rab7b	ENSRNOG00000039754

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955)

Protein

Protein identifiers

Ras-related protein Rab-7b — Q96AH8 (reviewed: Q96AH8)

All UniProt accessions (3): A0A096LP44, A0A096LPF0, Q96AH8

UniProt curated annotations — full annotation on UniProt →

Function. Controls vesicular trafficking from endosomes to the trans-Golgi network (TGN). Acts as a negative regulator of TLR9 signaling and can suppress TLR9-triggered TNFA, IL6, and IFNB production in macrophages by promoting TLR9 lysosomal degradation. Also negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Promotes megakaryocytic differentiation by increasing NF-kappa-B-dependent IL6 production and subsequently enhancing the association of STAT3 with GATA1. Not involved in the regulation of the EGF- and EGFR degradation pathway.

Subcellular location. Late endosome. Lysosome. Golgi apparatus. trans-Golgi network. Cytoplasmic vesicle. Phagosome. Phagosome membrane.

Tissue specificity. Expressed in heart, placenta, lung, skeletal muscle and peripheral blood leukocyte.

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 (3): NP_001157994, NP_001291768, NP_796377 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00071

UniProt features (11 total): binding site 5, short sequence motif 2, lipid moiety-binding region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AH8-F1	88.96	0.68

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 (5): 15–22; 34–40; 63–67; 124–127; 154–155

Post-translational modifications (3): 199, 186, 198

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 178 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_TOLL_LIKE_RECEPTOR_9_SIGNALING_PATHWAY, GOBP_VESICLE_ORGANIZATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_4_SIGNALING_PATHWAY, GOBP_VACUOLAR_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PHAGOLYSOSOME_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (11): endosome to lysosome transport (GO:0008333), protein transport (GO:0015031), positive regulation of interleukin-6 production (GO:0032755), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), negative regulation of toll-like receptor 9 signaling pathway (GO:0034164), late endosome to Golgi transport (GO:0034499), positive regulation of megakaryocyte differentiation (GO:0045654), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), cellular response to type II interferon (GO:0071346), phagosome-lysosome fusion (GO:0090385), regulation of immune system process (GO:0002682)

GO Molecular Function (5): G protein activity (GO:0003925), GTP binding (GO:0005525), nucleotide binding (GO:0000166), GTPase activity (GO:0003924), protein binding (GO:0005515)

GO Cellular Component (11): lysosome (GO:0005764), late endosome (GO:0005770), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), phagocytic vesicle membrane (GO:0030670), late endosome membrane (GO:0031902), phagocytic vesicle (GO:0045335), endosome (GO:0005768), membrane (GO:0016020), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Rab regulation of trafficking	2
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
endomembrane system	2
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
positive regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
toll-like receptor 9 signaling pathway	1
regulation of toll-like receptor 9 signaling pathway	1
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
megakaryocyte differentiation	1
positive regulation of myeloid cell differentiation	1
regulation of megakaryocyte differentiation	1
response to type II interferon	1
cellular response to cytokine stimulus	1
phagolysosome assembly	1
vesicle fusion	1
immune system process	1
regulation of biological process	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ribonucleoside triphosphate phosphatase activity	1
binding	1
lytic vacuole	1
endosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1112 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB7B	ARF1	P10947	591
RAB7B	SORT1	Q99523	546
RAB7B	VPS35	Q96QK1	523
RAB7B	VPS29	Q9UBQ0	520
RAB7B	TBC1D5	Q92609	497
RAB7B	VPS26A	O75436	489
RAB7B	SNX22	Q96L94	466
RAB7B	ERMARD	Q5T6L9	447
RAB7B	U2AF1	Q01081	439
RAB7B	DHRSX	Q8N5I4	433
RAB7B	VPS11	Q9H270	422
RAB7B	VPS33A	Q96AX1	421
RAB7B	VPS33B	Q9H267	415
RAB7B	CDKN2A	P42771	414
RAB7B	RILP	Q96NA2	411

IntAct

8 interactions, top by confidence:

A	B	Type	Score
APPBP2	RAB7B	psi-mi:“MI:0915”(physical association)	0.560
RAB7B	ATE1	psi-mi:“MI:0914”(association)	0.530
RAB7B	CHM	psi-mi:“MI:0914”(association)	0.530
RAP1B	RAB7B	psi-mi:“MI:0915”(physical association)	0.370
RAB7B	APPBP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): CHM (Affinity Capture-MS), CHML (Affinity Capture-MS), RABGGTA (Affinity Capture-MS), RABGGTB (Affinity Capture-MS), ATE1 (Affinity Capture-MS), RAB7B (Affinity Capture-Western), RAB7B (Affinity Capture-Western), RAB7B (Affinity Capture-Western), RAB7B (Two-hybrid), RAB7B (Affinity Capture-MS), SDHB (Affinity Capture-MS), CHM (Affinity Capture-MS), CHML (Affinity Capture-MS), RABGGTB (Affinity Capture-MS), RABGGTA (Affinity Capture-MS)

ESM2 similar proteins: E9Q9D5, E9R5S0, O42277, O94363, O95057, P01122, P11234, P22123, P22124, P24406, P36860, P48148, P48555, P49139, P61585, P61586, P61589, P62833, P62834, P62835, P62836, P79800, P87027, Q07983, Q08DE8, Q22038, Q4R379, Q5PR73, Q5R4B8, Q5R573, Q5R6S2, Q5REY6, Q5ZJW6, Q640R7, Q6DGL2, Q6IP71, Q6NUX8, Q7ZXH7, Q8VEA8, Q91Z61

Diamond homologs: C8VQY7, F1PTE3, G4MYS1, H9BW96, I1RMF2, O04157, O24461, O24466, O76173, O76742, O94655, O97572, P09527, P10536, P10949, P16976, P18067, P20791, P22125, P22128, P24408, P25228, P28186, P28187, P31022, P31584, P32939, P34140, P35286, P36411, P36586, P36861, P36864, P41924, P51149, P51150, P51151, P51153, P61020, P61021

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046651 (1:205987562 C>A), RS1000077648 (1:205987360 T>C), RS1000208746 (1:205982700 G>T), RS1000244978 (1:205992566 C>A), RS1000404032 (1:205976981 G>T), RS1000433707 (1:205976688 C>T), RS1000659264 (1:205983610 T>C), RS1000725847 (1:205982345 C>T), RS1000733444 (1:205978346 C>T), RS1000764932 (1:205978050 G>A,C), RS1000914423 (1:206004465 A>G), RS1000949641 (1:205983846 C>A,T), RS1000954364 (1:205998539 C>T), RS1001196756 (1:205988108 A>G), RS1001346110 (1:205983285 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
sodium arsenite	decreases expression, increases expression	5
Cadmium Chloride	decreases expression, increases abundance	3
bisphenol A	affects cotreatment, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
hydroquinone	decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Aldehydes	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cannabidiol	affects expression, affects response to substance	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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