RAB7A

Summary

RAB7A (RAB7A, member RAS oncogene family, HGNC:9788) is a protein-coding gene on chromosome 3q21.3, encoding Ras-related protein Rab-7a (P51149). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. It is a selective cancer dependency (DepMap: 42.5% of cell lines).

RAB family members are small, RAS-related GTP-binding proteins that are important regulators of vesicular transport. Each RAB protein targets multiple proteins that act in exocytic / endocytic pathways. This gene encodes a RAB family member that regulates vesicle traffic in the late endosomes and also from late endosomes to lysosomes. This encoded protein is also involved in the cellular vacuolation of the VacA cytotoxin of Helicobacter pylori. Mutations at highly conserved amino acid residues in this gene have caused some forms of Charcot-Marie-Tooth (CMT) type 2 neuropathies.

Source: NCBI Gene 7879 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease type 2 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 184 total — 4 pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 42.5% of screened cell lines
• MANE Select transcript: NM_004637

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9788
Approved symbol	RAB7A
Name	RAB7A, member RAS oncogene family
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000075785
Ensembl biotype	protein_coding
OMIM	602298
Entrez	7879

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 42 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000265062, ENST00000464496, ENST00000482525, ENST00000483906, ENST00000485280, ENST00000490093, ENST00000491681, ENST00000493186, ENST00000674589, ENST00000674593, ENST00000674748, ENST00000675342, ENST00000675497, ENST00000675712, ENST00000675864, ENST00000676147, ENST00000676214, ENST00000676425, ENST00000901014, ENST00000901015, ENST00000901016, ENST00000901017, ENST00000901018, ENST00000901019, ENST00000901020, ENST00000901021, ENST00000901022, ENST00000901023, ENST00000901024, ENST00000901025, ENST00000901026, ENST00000901027, ENST00000901028, ENST00000901029, ENST00000931691, ENST00000931692, ENST00000931693, ENST00000931694, ENST00000931695, ENST00000931696, ENST00000966841, ENST00000966842, ENST00000966843, ENST00000966844, ENST00000966845, ENST00000966846, ENST00000966847

RefSeq mRNA: 1 — MANE Select: NM_004637 NM_004637

CCDS: CCDS3052

Canonical transcript exons

ENST00000265062 — 6 exons

Exon	Start	End
ENSE00000778026	128806372	128806590
ENSE00000903897	128797943	128798069
ENSE00001047626	128807543	128807671
ENSE00001236693	128726183	128726359
ENSE00001314364	128813327	128814798
ENSE00003489442	128795360	128795420

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 214.1602 / max 3957.7926, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38457	191.3821	1827
38456	18.7459	1810
38474	2.2948	1253
38468	1.1019	792
38469	0.4658	233
38459	0.1181	41
38467	0.0515	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.08	gold quality
right lung	UBERON:0002167	98.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.77	gold quality
monocyte	CL:0000576	98.69	gold quality
prefrontal cortex	UBERON:0000451	98.68	gold quality
gastrocnemius	UBERON:0001388	98.68	gold quality
mononuclear cell	CL:0000842	98.66	gold quality
leukocyte	CL:0000738	98.64	gold quality
right adrenal gland cortex	UBERON:0035827	98.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.58	gold quality
colonic epithelium	UBERON:0000397	98.57	gold quality
left adrenal gland	UBERON:0001234	98.57	gold quality
right adrenal gland	UBERON:0001233	98.56	gold quality
muscle of leg	UBERON:0001383	98.56	gold quality
skin of leg	UBERON:0001511	98.53	gold quality
amniotic fluid	UBERON:0000173	98.51	gold quality
left adrenal gland cortex	UBERON:0035825	98.49	gold quality
ectocervix	UBERON:0012249	98.46	gold quality
descending thoracic aorta	UBERON:0002345	98.45	gold quality
skin of abdomen	UBERON:0001416	98.44	gold quality
omental fat pad	UBERON:0010414	98.44	gold quality
peritoneum	UBERON:0002358	98.43	gold quality
upper lobe of left lung	UBERON:0008952	98.42	gold quality
right coronary artery	UBERON:0001625	98.40	gold quality
lower esophagus mucosa	UBERON:0035834	98.40	gold quality
amygdala	UBERON:0001876	98.38	gold quality
esophagus mucosa	UBERON:0002469	98.38	gold quality
islet of Langerhans	UBERON:0000006	98.37	gold quality
spinal cord	UBERON:0002240	98.37	gold quality
esophagus	UBERON:0001043	98.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	16.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting RAB7A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4493	99.90	66.48	977

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 42.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• an endocytotic catalyst, a tandem regulator of thyroid hormone production (PMID:12034881)
• may be involved in the process of atherogenesis (PMID:12054610)
• Mutations in this protein cause Charcot-Marie-Tooth type 2B neuropathy. (PMID:12545426)
• Not a new major locus for Japanese oculocutaneous albinisms. (PMID:12850305)
• increase in the concentration of copper in the medium (189 microM) rapidly induces a redistribution of the MNK protein from early sorting endosomes, positive for Rab5-myc protein, to late endosomes, containing the Rab7-myc protein (PMID:14644159)
• All patients presented with a symmetric motor and sensory neuropathy, which was more pronounced in the lower limbs. Further, distal muscle wasting and impaired deep tendon reflexes were found.and linkage to chromosome 19q13.3. (PMID:15099588)
• Rab7 interacts with the Rab binding platform of REP-1 via an extended interface involving the Switch 1 and 2 regions. (PMID:15186776)
• Results show a role for Rab7 in the final maturation of late autophagic vacuoles. (PMID:15340014)
• This study report a family with autosomal dominant ulcero-mutilating neuropathy and Sequencing the RAB7 gene showed a novel heterozygous A to C mutation, changing asparagine to threonine at codon 161. (PMID:15455439)
• ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 protein and translocates copper from the cytosol to the late endosomal lumen, participating in biliary copper excretion via lysosomes (PMID:15681833)
• The crystal structure of Rab7-GTP in complex with the Rab7 binding domain of RILP reveals that Rab7 interacts with RILP specifically via two distinct areas. (PMID:15933719)
• The data together indicate that RILP, as already demonstrated for several other Rab effector proteins, is capable of self-association, thus probably forming a homo-dimer. (PMID:15996637)
• ORP1L binds to Rab7, modifies its functional cycle, and can interfere with lysosome organization and endocytic membrane trafficking. (PMID:16176980)
• rab7 regulates the endocytic trafficking of the EGF.EGFR complex by regulating its lysosomal degradation (PMID:16282324)
• Hence, RILPsv provides an extra dimension to the control of vesicle fusion and transport by the small GTPase Rab7. (PMID:16631113)
• Rab7 controls microtubule-mediated transport of early and Rab27a the subsequent actin-dependent transport of mature melanosomes. (PMID:16965270)
• GTP-bound form of Rab7 promotes melanogenesis through the regulation of gp100 maturation in melanoma cells. (PMID:17625594)
• RIDalpha coordinates recruitment of these GTP-Rab7 effectors to compartments that would ordinarily be perceived as early endosomes, thereby promoting the degradation of selected cargo. (PMID:18039930)
• All tested CMT2B-associated Rab7 mutations are mechanistically similar, suggesting that activated forms of the Rab7 are responsible for CMT2B disease. (PMID:18272684)
• The biochemical and functional properties of the Rab7 K157N mutated protein were investigated. (PMID:18501189)
• cholesterol accumulation can have a detrimental effect on phagosome maturation by impairing the activation of Rab7 (PMID:18955491)
• Data suggest that translocation of ATP7B takes place independently of Rab7-regulated endosomal traffic, and that Murr1 plays a role in a later step of the copper excretion pathway but is not involved in the translocation of the Wilson disease protein. (PMID:18974300)
• Rab GTPase regulation of VEGFR2 trafficking and signaling in endothelial cells; Endothelial cell migration was increased by Rab5a depletion but decreased by Rab7a depletion (PMID:19372461)
• the central role of Rab7 in endosomal traffic and summarize the studies focusing on the participation of Rab7 in disease pathogenesis. (PMID:19392663)
• Results describe how ORP1L contacts VAP to control Rab7-RILP-p150 Glued and late endosome positioning. (PMID:19564404)
• These results suggest that the dissociation of Rab7 from M.tb phagosome is the important process in inhibition of phagolysosome biogenesis. (PMID:19580780)
• mechanisms of GAS-containing autophagosome-like vacuoles formation includes not only the common machinery of autophagy, but also Rab7 as an additional component, which is dispensable in canonical autophagosome formation. (PMID:19956673)
• Disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity. (PMID:20028791)
• although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence (PMID:20363736)
• Rab5 and Rab7, were associated with the pathway of autophagosome formation and the fate of intracellular group A streptococcus. (PMID:20472552)
• Mutations in LITAF, RAB7, LMNA, and MTMR2 genes are rare in Chinese Charcot-Marie-Tooth disease (CMT) patients. (PMID:20709679)
• Results indicate selective upregulation of Both rab5 and rab7 levels within basal forebrain, frontal cortex, and hippocampus in mild cognitive impairment and Alzheimer’s disease. (PMID:20847427)
• Rubicon serves as a previously unknown Rab7 effector to ensure the proper progression of the endocytic pathway. (PMID:20974968)
• Results suggest that Rab7 may play a role in secretory lysosome movement toward the centrosome by interacting with RILP to recruit the minus-end motor, dynein. (PMID:21438969)
• Upregulated expresssion of rab4, rab5, rab7, and rab27 correlates with antemortem measures of cognitive decline in individuals with mild cognitive impariment and Alzheimer disease. (PMID:21669283)
• results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release; results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle (PMID:22072966)
• the tail-domain of phafin1 provides lysosomal targeting signature and the ability to induce autophagy that is mediated by Rab7 signaling. (PMID:22115783)
• Inhibition of endosomal maturation-with siRNAs or dominant negative mutants targeting Rab5 and Rab7-inhibited infection and prevented release of Echovirus 7 RNA into the cell. (PMID:22496312)
• Data indicate that Rab7 siRNA knockdown causes increased E-cadherin. (PMID:22638108)
• This study found that significant evidence of association with RAB7 (VEGAS p = 0.018) in patient with Alzheimer disease. (PMID:22673115)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab7a	ENSDARG00000020497
danio_rerio	rab7b	ENSDARG00000021287
danio_rerio	RAB7A	ENSDARG00000087243
mus_musculus	Rab7	ENSMUSG00000079477
rattus_norvegicus	Rab7a	ENSRNOG00000012247
drosophila_melanogaster	Rab7	FBGN0015795

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), 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-7a — P51149 (reviewed: P51149)

All UniProt accessions (12): P51149, A0A158RFU6, A0A6Q8PF79, A0A6Q8PG52, A0A6Q8PGE6, A0A6Q8PH84, C9IZZ0, C9J4S4, C9J4V0, C9J592, C9J7D1, C9J8S3

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. In its active state, RAB7A binds to a variety of effector proteins playing a key role in the regulation of endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Also plays a central role in growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in the fusion of phagosomes with lysosomes. In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA. Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation. Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway. Required for the exosomal release of SDCBP, CD63 and syndecan. Required for vesicular trafficking and cell surface expression of ACE2. May play a role in PRPH neuronal intermediate filament assembly.

Subunit / interactions. The GTP-bound form interacts with RAC1. Interacts with NTRK1/TRKA. Interacts with C9orf72. Interacts with CHM, the substrate-binding subunit of the Rab geranylgeranyltransferase complex. Interacts with RILP. Interacts with PSMA7. Interacts with RNF115. Interacts with FYCO1. Interacts with the PIK3C3/VPS34-PIK3R4 complex. The GTP-bound form interacts with OSBPL1A. Interacts with CLN3. Does not interact with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and HPS4). Interacts with CLN5. Interacts with PLEKHM1 (via N- and C-terminus). Interacts with PRPH; the interaction is direct. Interacts with VPS13A. The GDP-bound form interacts with RIMOC1. Interacts with the MON1A-CCZ1B complex and this interaction is enhanced in the presence of RIMOC1. Interacts with VPS39 and VPS41. Interacts with RUFY4. Forms a ternary complex with LAMP2 and RUFY4; the interaction with LAMP2 is mediated by RUFY4 (via RUN and coiled coil domains).

Subcellular location. Cytoplasmic vesicle. Phagosome membrane. Late endosome membrane. Lysosome membrane. Melanosome membrane. Autophagosome membrane. Lipid droplet. Endosome membrane. Mitochondrion membrane.

Tissue specificity. Widely expressed; high expression found in skeletal muscle.

Post-translational modifications. Deubiquitination at Lys-191 and Lys-194 by USP32. Phosphorylated at Ser-72 by LRRK1; phosphorylation is dependent on protein kinase C (PKC) activation of LRRK1. Prenylated. Prenylation is required for association with cellular membranes.

Disease relevance. Charcot-Marie-Tooth disease, axonal, type 2B (CMT2B) [MIM:600882] A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry.

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 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 (1): NP_004628* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (63 total): binding site 20, helix 8, mutagenesis site 7, strand 7, sequence variant 5, sequence conflict 4, modified residue 3, short sequence motif 2, lipid moiety-binding region 2, cross-link 2, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
1T91	X-RAY DIFFRACTION	1.9
6IYB	X-RAY DIFFRACTION	2.09
7F6J	X-RAY DIFFRACTION	2.1
8ZQ3	X-RAY DIFFRACTION	2.43
8KB8	X-RAY DIFFRACTION	2.49
3LAW	X-RAY DIFFRACTION	2.8
6WCW	X-RAY DIFFRACTION	2.8
9LOL	ELECTRON MICROSCOPY	2.85
1YHN	X-RAY DIFFRACTION	3
9L0D	ELECTRON MICROSCOPY	3.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51149-F1	88.98	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 (20): 22; 23; 34; 35; 37; 40; 40; 63; 66; 125; 126; 128 …

Post-translational modifications (7): 2, 72, 207, 205, 207, 191, 194

Mutagenesis-validated functional residues (7):

Position	Phenotype
8	abolishes interaction with rilp and reduces its localization to late endosomal/lysosomal compartments.
10	abolishes interaction with rilp and localization to late endosomal/lysosomal compartments.
22	abolishes localization on late endosomes, lysosomes and phagosomes and reduces phagosomal fusions. abolishes association
67	does not abolish localization on late endosomes, lysosomes and phagosomes and does not reduce phagosomal fusions. no los
180	abolishes interaction with rilp and localization to late endosomal/lysosomal compartments.
182	does not abolish interaction with rilp and localization to late endosomal/lysosomal compartments. does not abolish inter
183	does not abolish interaction with rilp and localization to late endosomal/lysosomal compartments. does not abolish inter

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-6798695	Neutrophil degranulation
R-HSA-8854214	TBC/RABGAPs
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-9636383	Prevention of phagosomal-lysosomal fusion
R-HSA-9636569	Suppression of autophagy

MSigDB gene sets: 482 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GCANCTGNY_MYOD_Q6, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION

GO Biological Process (30): autophagosome assembly (GO:0000045), protein targeting to lysosome (GO:0006622), endocytosis (GO:0006897), epidermal growth factor catabolic process (GO:0007174), endosome to lysosome transport (GO:0008333), response to bacterium (GO:0009617), protein transport (GO:0015031), lipid catabolic process (GO:0016042), viral release from host cell (GO:0019076), protein to membrane docking (GO:0022615), synaptic vesicle recycling via endosome (GO:0036466), retrograde transport, endosome to Golgi (GO:0042147), early endosome to late endosome transport (GO:0045022), bone resorption (GO:0045453), positive regulation of protein catabolic process (GO:0045732), positive regulation of viral process (GO:0048524), establishment of vesicle localization (GO:0051650), protein localization to lysosome (GO:0061462), lipophagy (GO:0061724), phagosome maturation (GO:0090382), phagosome acidification (GO:0090383), phagosome-lysosome fusion (GO:0090385), neurotransmitter receptor transport, postsynaptic endosome to lysosome (GO:0098943), endosome to plasma membrane protein transport (GO:0099638), negative regulation of exosomal secretion (GO:1903542), positive regulation of exosomal secretion (GO:1903543), negative regulation of intralumenal vesicle formation (GO:1905366), lipid metabolic process (GO:0006629), autophagy (GO:0006914), vesicle-mediated transport in synapse (GO:0099003)

GO Molecular Function (9): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), small GTPase binding (GO:0031267), retromer complex binding (GO:1905394), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (29): autophagosome membrane (GO:0000421), mitochondrion (GO:0005739), lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), Golgi apparatus (GO:0005794), lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), secretory granule membrane (GO:0030667), phagocytic vesicle membrane (GO:0030670), synaptic vesicle membrane (GO:0030672), late endosome membrane (GO:0031902), mitochondrial membrane (GO:0031966), melanosome membrane (GO:0033162), phagophore assembly site membrane (GO:0034045), ciliary transition zone (GO:0035869), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), alveolar lamellar body (GO:0097208), presynaptic endosome (GO:0098830), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020), retromer complex (GO:0030904), cytoplasmic vesicle (GO:0031410), bounding membrane of organelle (GO:0098588)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
RHO GTPase cycle	10
Rab regulation of trafficking	2
Adaptive Immune System	1
Innate Immune System	1
Post-translational protein modification	1
Suppression of phagosomal maturation	1
Response of Mtb to phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
lysosomal transport	2
vesicle-mediated transport	2
protein catabolic process	2
intercellular transport	2
viral process	2
guanyl ribonucleotide binding	2
intracellular membrane-bounded organelle	2
endosome	2
cellular anatomical structure	2
membrane	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
protein targeting to vacuole	1
protein localization to lysosome	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
negative regulation of epidermal growth factor receptor signaling pathway	1
response to other organism	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
lipid metabolic process	1
catabolic process	1
viral life cycle	1
exit from host cell	1
membrane docking	1
synaptic vesicle recycling	1
intracellular transport	1
synaptic vesicle endosomal processing	1
endosomal transport	1
cytosolic transport	1

Protein interactions and networks

STRING

2784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB7A	RILP	Q96NA2	788
RAB7A	TBC1D15	Q8TC07	742
RAB7A	VPS26A	O75436	741
RAB7A	SNX3	O60493	695
RAB7A	TBC1D5	Q92609	695
RAB7A	LAMP1	P11279	688
RAB7A	VPS39	Q96JC1	664
RAB7A	FYCO1	Q9BQS8	655
RAB7A	VPS29	Q9UBQ0	642
RAB7A	EEA1	Q15075	636
RAB7A	VPS35	Q96QK1	631
RAB7A	PLEKHM1	Q9Y4G2	606
RAB7A	LAMP2	P13473	596
RAB7A	PSMB2	P31145	552
RAB7A	INF2	Q27J81	543

IntAct

243 interactions, top by confidence:

A	B	Type	Score
VPS39		psi-mi:“MI:0914”(association)	0.960
RILP	RAB7A	psi-mi:“MI:0407”(direct interaction)	0.930
RILP	RAB7A	psi-mi:“MI:0915”(physical association)	0.930
RAB7A	RILP	psi-mi:“MI:0915”(physical association)	0.930
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
PLEKHM1	RAB7A	psi-mi:“MI:0915”(physical association)	0.800
PLEKHM1	RAB7A	psi-mi:“MI:0403”(colocalization)	0.800
RAB7A	PLEKHM1	psi-mi:“MI:0915”(physical association)	0.800
RAB7A	PLEKHM1	psi-mi:“MI:0403”(colocalization)	0.800
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
OSBPL1A	RAB7A	psi-mi:“MI:0407”(direct interaction)	0.670
OSBPL1A	RAB7A	psi-mi:“MI:0915”(physical association)	0.670
OAZ1	AZIN1	psi-mi:“MI:0914”(association)	0.640
CFTR	RAB5A	psi-mi:“MI:0914”(association)	0.610

BioGRID (1199): RAB7A (Affinity Capture-MS), KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), RAB7A (Affinity Capture-MS), RAB7A (Affinity Capture-MS), RAB7A (Affinity Capture-MS), RAB7A (Affinity Capture-MS), SNX3 (Reconstituted Complex), VPS26A (Reconstituted Complex), VPS35 (Reconstituted Complex), VPS29 (Reconstituted Complex), VPS11 (Reconstituted Complex), VPS16 (Reconstituted Complex), VPS18 (Reconstituted Complex), VPS39 (Reconstituted Complex)

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

15 interactions.

A	Effect	B	Mechanism
PTEN	“up-regulates activity”	RAB7A	dephosphorylation
RAB7A	“down-regulates activity”	ALS2	binding
RAB7A	up-regulates	“Late macropinosomes”
RAB5A	“down-regulates activity”	RAB7A	binding
LRRK1	“up-regulates activity”	RAB7A	phosphorylation
RAB7A	“up-regulates activity”	RAC1	binding
RAB7A	“down-regulates activity”	NTRK1	binding
RAB7A	“up-regulates activity”	PIK3C3	“guanine nucleotide exchange factor”
RAB7A	“up-regulates activity”	PSMA7	binding
ATP6AP1	“up-regulates activity”	RAB7A	binding
“MON1-CCZ1 guanyl-nucleotide exchange factor complex, MON1B variant”	“up-regulates activity”	RAB7A	“guanine nucleotide exchange factor”
“MON1-CCZ1 guanyl-nucleotide exchange factor complex, MON1A variant”	“up-regulates activity”	RAB7A	“guanine nucleotide exchange factor”
“MON1-CCZ1B guanyl-nucleotide exchange factor complex, MON1A variant”	“up-regulates activity”	RAB7A	“guanine nucleotide exchange factor”
“MON1-CCZ1B guanyl-nucleotide exchange factor complex, MON1B variant”	“up-regulates activity”	RAB7A	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 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
MAP kinase activation	6	15.6×	5e-04
Interleukin-17 signaling	6	12.8×	1e-03
MyD88 cascade initiated on plasma membrane	7	12.0×	5e-04
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	7	11.2×	5e-04
MyD88 dependent cascade initiated on endosome	7	11.2×	5e-04
Toll Like Receptor 10 (TLR10) Cascade	6	10.9×	2e-03
Toll Like Receptor 5 (TLR5) Cascade	6	10.9×	2e-03
Toll Like Receptor 3 (TLR3) Cascade	6	9.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	11	5.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	69
Likely benign	69
Benign	24

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
637404	NM_004637.6(RAB7A):c.482A>T (p.Asn161Ile)	Pathogenic
7345	NM_004637.6(RAB7A):c.385C>T (p.Leu129Phe)	Pathogenic
7346	NM_004637.6(RAB7A):c.484G>A (p.Val162Met)	Pathogenic
846631	NM_004637.6(RAB7A):c.471G>T (p.Lys157Asn)	Pathogenic

SpliceAI

1578 predictions. Top by Δscore:

Variant	Effect	Δscore
3:128795358:A:AG	acceptor_gain	1.0000
3:128795359:G:GC	acceptor_gain	1.0000
3:128795359:GTTT:G	acceptor_gain	1.0000
3:128795417:CTGGG:C	donor_loss	1.0000
3:128795419:GGGTA:G	donor_loss	1.0000
3:128795420:GGTAA:G	donor_loss	1.0000
3:128795421:GT:G	donor_loss	1.0000
3:128795422:T:TC	donor_loss	1.0000
3:128797935:A:AG	acceptor_gain	1.0000
3:128797936:A:G	acceptor_gain	1.0000
3:128797938:TTCA:T	acceptor_loss	1.0000
3:128797940:CA:C	acceptor_loss	1.0000
3:128797941:A:AC	acceptor_loss	1.0000
3:128797941:A:AG	acceptor_gain	1.0000
3:128797942:G:C	acceptor_gain	1.0000
3:128797942:G:GT	acceptor_gain	1.0000
3:128797942:GA:G	acceptor_gain	1.0000
3:128797942:GAGT:G	acceptor_gain	1.0000
3:128797942:GAGTC:G	acceptor_gain	1.0000
3:128798034:G:GT	donor_gain	1.0000
3:128798065:TGCAG:T	donor_gain	1.0000
3:128798066:GCAG:G	donor_gain	1.0000
3:128798066:GCAGG:G	donor_gain	1.0000
3:128798067:CAGGT:C	donor_loss	1.0000
3:128798069:GGT:G	donor_loss	1.0000
3:128798070:G:GG	donor_gain	1.0000
3:128798071:T:G	donor_loss	1.0000
3:128806371:GATAT:G	acceptor_gain	1.0000
3:128806586:GACAA:G	donor_gain	1.0000
3:128806587:ACAAG:A	donor_loss	1.0000

AlphaMissense

1375 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:128795397:G:C	K10N	1.000
3:128795397:G:T	K10N	1.000
3:128795410:G:A	G15R	1.000
3:128795410:G:C	G15R	1.000
3:128795411:G:A	G15E	1.000
3:128795411:G:T	G15V	1.000
3:128797947:G:A	G20R	1.000
3:128797947:G:C	G20R	1.000
3:128797947:G:T	G20W	1.000
3:128797948:G:A	G20E	1.000
3:128797948:G:T	G20V	1.000
3:128797950:A:C	K21Q	1.000
3:128797951:A:T	K21M	1.000
3:128797952:G:C	K21N	1.000
3:128797952:G:T	K21N	1.000
3:128797954:C:T	T22I	1.000
3:128797986:T:C	F33L	1.000
3:128797988:C:A	F33L	1.000
3:128797988:C:G	F33L	1.000
3:128798008:C:T	T40I	1.000
3:128798011:T:A	I41K	1.000
3:128798013:G:A	G42R	1.000
3:128798013:G:C	G42R	1.000
3:128798014:G:A	G42E	1.000
3:128798017:C:A	A43D	1.000
3:128798022:T:C	F45L	1.000
3:128798023:T:C	F45S	1.000
3:128798024:T:A	F45L	1.000
3:128798024:T:G	F45L	1.000
3:128798026:T:C	L46P	1.000

dbSNP variants (sampled 300 via entrez): RS1000028450 (3:128743423 G>A), RS1000088173 (3:128805778 A>T), RS1000125580 (3:128782000 G>A,C,T), RS1000170121 (3:128801205 T>C,G), RS1000218905 (3:128759711 G>A), RS1000249721 (3:128795060 G>A), RS1000250039 (3:128770845 T>TA), RS1000258989 (3:128765269 C>T), RS1000313000 (3:128756010 A>G), RS1000321672 (3:128807774 T>C), RS1000328241 (3:128749337 A>G), RS1000341699 (3:128782887 C>G), RS1000348463 (3:128788227 T>C), RS1000367606 (3:128726720 A>G,T), RS1000418424 (3:128738645 C>T)

Disease associations

OMIM: gene MIM:602298 | disease phenotypes: MIM:600882, MIM:118220

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 2	Definitive	Autosomal dominant
Charcot-Marie-Tooth disease type 2B	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 2	Definitive	AD

Mondo (3): Charcot-Marie-Tooth disease type 2B (MONDO:0010949), Charcot-Marie-Tooth disease (MONDO:0015626), Charcot-Marie-Tooth disease type 2 (MONDO:0018993)

Orphanet (3): Autosomal dominant Charcot-Marie-Tooth disease type 2B (Orphanet:99936), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Hereditary sodium channelopathy-related small fibers neuropathy (Orphanet:306577)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000763	Sensory neuropathy
HP:0001218	Autoamputation
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001761	Pes cavus
HP:0001763	Pes planus
HP:0001765	Hammertoe
HP:0001810	Dystrophic toenail
HP:0001868	Autoamputation of foot
HP:0001886	Foot osteomyelitis
HP:0002380	Fasciculations
HP:0002460	Distal muscle weakness
HP:0003376	Steppage gait
HP:0003378	Axonal degeneration/regeneration
HP:0003380	Decreased number of peripheral myelinated nerve fibers
HP:0003384	Peripheral axonal atrophy
HP:0003431	Decreased motor nerve conduction velocity
HP:0003438	Absent Achilles reflex
HP:0003474	Somatic sensory dysfunction
HP:0003621	Juvenile onset
HP:0003693	Distal amyotrophy
HP:0006937	Impaired distal tactile sensation
HP:0007141	Sensorimotor neuropathy
HP:0008944	Distal lower limb amyotrophy
HP:0009027	Foot dorsiflexor weakness
HP:0009053	Distal lower limb muscle weakness
HP:0009830	Peripheral neuropathy
HP:0033383	Decreased compound muscle action potential amplitude

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007989_6	Facial morphology traits (63 three-dimensional facial segments)	1.000000e-17
GCST008157_1	Body fat mass	9.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
C537989	Charcot-Marie-Tooth disease, Type 2B (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105784 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4548	RAB7A		0.00	0

ChEMBL bioactivities

61 potent at pChembl≥5 of 61 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.66	EC50	22	nM	CHEMBL1328505
7.64	EC50	22.67	nM	CHEMBL1328505
7.62	EC50	24	nM	CHEMBL1328505
7.60	EC50	25	nM	CHEMBL4097338
7.59	Kd	25.83	nM	CHEMBL384759
7.48	EC50	33	nM	CHEMBL4098837
7.46	EC50	35	nM	CHEMBL4098837
7.46	EC50	35	nM	CHEMBL4080794
7.43	EC50	37.33	nM	CHEMBL1328505
7.43	EC50	37	nM	CHEMBL4080794
7.42	Kd	37.62	nM	CHEMBL384759
7.42	EC50	38	nM	CHEMBL1328505
7.40	EC50	40	nM	CHEMBL1328505
7.20	EC50	63	nM	CHEMBL4091094
7.18	EC50	66	nM	CHEMBL4091094
7.13	EC50	74	nM	CHEMBL4068483
7.11	Kd	78.14	nM	GUANOSINE TRIPHOSPHATE
7.11	EC50	77	nM	CHEMBL4069652
7.09	EC50	82	nM	CHEMBL4068483
7.04	Kd	92.12	nM	CHEMBL384759
7.02	EC50	95	nM	CHEMBL4069652
7.01	EC50	97	nM	CHEMBL4089622
6.96	Kd	109.2	nM	CHEMBL384759
6.96	EC50	110	nM	CHEMBL4065916
6.91	Kd	123.6	nM	GUANOSINE TRIPHOSPHATE
6.85	EC50	140	nM	CHEMBL4072366
6.85	EC50	140	nM	CHEMBL4099312
6.85	EC50	140	nM	CHEMBL4087327
6.85	EC50	140	nM	CHEMBL4089622
6.82	EC50	150	nM	CHEMBL4060979
6.77	EC50	170	nM	CHEMBL4072366
6.72	EC50	192	nM	CHEMBL4087327
6.66	EC50	220	nM	CHEMBL4070133
6.62	EC50	240	nM	CHEMBL4065916
6.57	EC50	270	nM	CHEMBL4072864
6.57	EC50	270	nM	CHEMBL4087327
6.54	EC50	290	nM	CHEMBL4097914
6.52	EC50	300	nM	CHEMBL4072864
6.50	EC50	320	nM	CHEMBL4097914
6.50	EC50	320	nM	CHEMBL4060979
6.44	EC50	360	nM	CHEMBL4064268
6.39	EC50	410	nM	CHEMBL4092004
6.37	EC50	430	nM	CHEMBL4095262
6.36	Kd	440.1	nM	CHEMBL5653589
6.36	ED50	440.1	nM	CHEMBL5653589
6.35	Kd	443.8	nM	GUANOSINE TRIPHOSPHATE
6.34	EC50	460	nM	CHEMBL4079309
6.33	EC50	470	nM	CHEMBL4070133
6.30	EC50	500	nM	CHEMBL4065916
6.28	EC50	520	nM	CHEMBL4092004

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149179: Binding affinity to human RAB7A incubated for 45 mins by Kinobead based pull down assay	kd	0.4401	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149179: Binding affinity to human RAB7A incubated for 45 mins by Kinobead based pull down assay	kd	6.5923	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
bisphenol A	increases expression, decreases methylation	3
Cisplatin	affects expression, decreases expression, affects cotreatment	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
sodium arsenite	increases expression, increases abundance	2
Lead	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, increases expression, affects cotreatment, affects localization	1
ochratoxin A	affects binding	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
monomethylarsonous acid	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
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1

ChEMBL screening assays

33 unique, capped per target: 33 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3992331	Binding	Binding affinity to Rab7 GTPase L129F mutant (unknown origin) assessed as equilibrium dissociation constant	Rab7 GTPase inhibitors and related methods of treatment

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2D4	Abcam HeLa RAB7A KO	Cancer cell line	Female
CVCL_D7ET	HeLa M RAB7A-KO	Cancer cell line	Female
CVCL_D7EU	HeLa M TBK1-KO + RAB7-KO	Cancer cell line	Female
CVCL_D7EW	HeLa M RAB7A-KO + mCherry-RAB7	Cancer cell line	Female
CVCL_D7EX	HeLa M RAB7A-KO + mCherry-RAB7-S72A	Cancer cell line	Female
CVCL_TI24	HAP1 RAB7A (-) 1	Cancer cell line	Male
CVCL_TI25	HAP1 RAB7A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00271635	PHASE2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	PHASE2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	PHASE2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	PHASE2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	PHASE2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	PHASE2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	PHASE2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	PHASE2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	PHASE2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT01289704	PHASE2/PHASE3	UNKNOWN	Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
NCT00541164	PHASE1/PHASE2	COMPLETED	Effects of Coenzyme Q10 on Charcot-Marie-Tooth Disease
NCT05361031	PHASE1/PHASE2	COMPLETED	The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)
NCT07223632	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient
NCT00149045	Not specified	COMPLETED	Follow up and Observation of Charcot Marie Tooth Disease in Families
NCT01193075	Not specified	RECRUITING	Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others
NCT01203085	Not specified	COMPLETED	Development of Charcot Marie Tooth Disease (CMT) Pediatric Scale for Children With CMT
NCT01455623	Not specified	COMPLETED	Development and Validation of a Disability Severity Index for CMT
NCT01918826	Not specified	UNKNOWN	Evaluation of the Analgesic Efficiency of the Transcutaneous Neurostimulation in the Charcot Syndrome Marie Tooth on the Pains of Lower Limbs
NCT02001038	Not specified	COMPLETED	Survey of Current Management of Orthopaedic Complications in CMT Patients
NCT02011204	Not specified	COMPLETED	Study of Electrical Impedance Myography (EIM) in ALS
NCT02194010	Not specified	COMPLETED	Disability Severity Scale (DSI) and Hereditary Motor and Sensory Neuropathy Overall Disability Scale (HMSN-R-ODS)
NCT02429947	Not specified	COMPLETED	An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients
NCT02532244	Not specified	COMPLETED	Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02788734	Not specified	COMPLETED	Patient Reported Outcomes Measures (PROM) in Carpal Tunnel Therapies in Patients With Inherited Neuropathies
NCT02979145	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Infant Scale (INC-6611)
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03460951	Not specified	COMPLETED	Diffusion Tensor Imaging in Chronic Inflammatory Demyelinating Polyneuropathy (PIDC)
NCT03715283	Not specified	COMPLETED	Change in MUNIX in Patients With CMT1A Undergoing a Home Ankle Strengthening Program Versus Standard of Care
NCT03782883	Not specified	COMPLETED	The Impact of Charcot-Marie-Tooth Disease in the Real World
NCT03810508	Not specified	TERMINATED	A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)
NCT03966287	Not specified	COMPLETED	Analysis of Pain and Quality of Life in Patients With Charcot-Marie-Tooth Neuropathy (CMT)
NCT04010188	Not specified	RECRUITING	A Registered Cohort Study on Charcot-Marie-Tooth Disease
NCT04283175	Not specified	COMPLETED	Validation Study of Posturology Platforms for Evaluating Postural Control of Hemiparetic and Neuro-muscular Patients
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument
NCT04786522	Not specified	COMPLETED	Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
NCT04967716	Not specified	UNKNOWN	Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases
NCT04980807	Not specified	COMPLETED	Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls