RAB7A

RAB7A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Basic information

Region (hg38): 3:128693668-128825942

Previous symbols: [ "RAB7", "CMT2B" ]

Links

ENSG00000075785 ∙ NCBI:7879 ∙ OMIM:602298 ∙ HGNC:9788 ∙ Uniprot:P51149 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease type 2B (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 2B (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease type 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, axonal, type 2B	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	7573046; 9219740; 11094113; 12545426; 17060578; 22302274

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB7A gene.

• Charcot-Marie-Tooth disease type 2B (134 variants)
• not provided (42 variants)
• Inborn genetic diseases (14 variants)
• Charcot-Marie-Tooth disease (13 variants)
• not specified (9 variants)
• Charcot-Marie-Tooth disease type 2 (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB7A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				25	1	26
missense	4		32	3		39
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	8	1	12
non coding			31	34	19	84
Total	4	0	63	62	20

Variants in RAB7A

This is a list of pathogenic ClinVar variants found in the RAB7A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-128726153-C-T		Charcot-Marie-Tooth disease type 2B	Benign (Jan 13, 2018)
3-128726153-C-CGGCGGT		Charcot-Marie-Tooth disease type 2	Conflicting classifications of pathogenicity (Sep 01, 2022)
3-128726164-G-T		Charcot-Marie-Tooth disease type 2B	Uncertain significance (Jan 13, 2018)
3-128726214-G-A		Charcot-Marie-Tooth disease type 2B	Uncertain significance (Jan 12, 2018)
3-128726222-G-C		Charcot-Marie-Tooth disease type 2B	Uncertain significance (Jan 13, 2018)
3-128726253-C-T		Charcot-Marie-Tooth disease type 2B	Benign (Jan 13, 2018)
3-128726271-C-G		Charcot-Marie-Tooth disease type 2B	Benign/Likely benign (Nov 18, 2020)
3-128726297-TCTC-T		Charcot-Marie-Tooth disease type 2	Conflicting classifications of pathogenicity (Sep 01, 2022)
3-128726307-G-A		Charcot-Marie-Tooth disease type 2B	Uncertain significance (Jan 12, 2018)
3-128726339-G-T		not specified • Charcot-Marie-Tooth disease type 2B	Benign (Jan 13, 2018)
3-128726350-A-G		Charcot-Marie-Tooth disease type 2B • not specified • RAB7A-related disorder	Conflicting classifications of pathogenicity (Jul 26, 2022)
3-128726387-G-T			Likely benign (Oct 27, 2021)
3-128726579-G-T			Likely benign (Jan 20, 2021)
3-128795080-A-G			Benign (Jun 19, 2018)
3-128795218-T-G			Benign (Jun 19, 2018)
3-128795348-T-C		not specified	Likely benign (Dec 31, 2015)
3-128795362-T-C		not specified	Likely benign (May 27, 2016)
3-128795373-C-G		Charcot-Marie-Tooth disease type 2B	Likely benign (Jun 19, 2022)
3-128795385-A-G		Charcot-Marie-Tooth disease type 2B	Likely benign (Jul 30, 2020)
3-128795388-G-A		Charcot-Marie-Tooth disease type 2B • Charcot-Marie-Tooth disease • Inborn genetic diseases • RAB7A-related disorder	Likely benign (Dec 05, 2023)
3-128795427-T-C		Charcot-Marie-Tooth disease type 2B	Likely benign (Aug 08, 2020)
3-128795429-C-G		Charcot-Marie-Tooth disease type 2B	Likely benign (Jun 20, 2023)
3-128795434-G-T		Charcot-Marie-Tooth disease type 2B	Likely benign (Dec 18, 2023)
3-128795495-G-A			Likely benign (Aug 03, 2018)
3-128795653-T-C			Likely benign (Jun 16, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB7A	protein_coding	protein_coding	ENST00000265062	5	88675

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.969	0.0306	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	46	115	0.401	0.00000675	1375
Missense in Polyphen		1	35.511	0.02816		440
Synonymous	0.296	41	43.5	0.943	0.00000254	378
Loss of Function	3.04	0	10.8	0.00	5.53e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator in 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. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as 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. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). 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 (PubMed:11179213, PubMed:12944476, PubMed:14617358, PubMed:20028791, PubMed:21255211). 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 (By similarity). Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000250|UniProtKB:P51150, ECO:0000269|PubMed:11179213, ECO:0000269|PubMed:12944476, ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:20028791, ECO:0000269|PubMed:22660413}.
• Pathway: Salmonella infection - Homo sapiens (human);Endocytosis - Homo sapiens (human);Phagosome - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Neutrophil degranulation;Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Rab regulation of trafficking;Posttranslational regulation of adherens junction stability and dissassembly;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation;IL8- and CXCR2-mediated signaling events;IL12-mediated signaling events (Consensus)

Intolerance Scores

• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.503
• hipred: Y
• hipred_score: 0.783
• ghis: 0.623

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.945

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rab7
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; embryo phenotype; immune system phenotype; cellular phenotype

Gene ontology

• Biological process: autophagosome assembly;protein targeting to lysosome;intracellular protein transport;endocytosis;epidermal growth factor catabolic process;endosome to lysosome transport;protein transport;lipid catabolic process;viral release from host cell;antigen processing and presentation of exogenous peptide antigen via MHC class II;protein to membrane docking;Rab protein signal transduction;retrograde transport, endosome to Golgi;neutrophil degranulation;early endosome to late endosome transport;positive regulation of protein catabolic process;positive regulation of viral process;lipophagy;phagosome maturation;phagosome acidification;phagosome-lysosome fusion;multi-organism intracellular transport;negative regulation of exosomal secretion;positive regulation of exosomal secretion;negative regulation of intralumenal vesicle formation
• Cellular component: autophagosome membrane;lysosome;lysosomal membrane;late endosome;vacuolar membrane;Golgi apparatus;lipid droplet;cytosol;plasma membrane;endosome membrane;secretory granule membrane;phagocytic vesicle membrane;retromer complex;late endosome membrane;extrinsic component of lysosome membrane;melanosome membrane;phagophore assembly site membrane;phagocytic vesicle;extracellular exosome
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding;retromer complex binding