RAB7A
RAB7A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases
Basic information
Region (hg38): 3:128693669-128825942
Previous symbols: [ "RAB7", "CMT2B" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Charcot-Marie-Tooth disease type 2B (4 variants)
- Charcot-Marie-Tooth disease (3 variants)
- not provided (2 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. These statistics are base on transcript: . Only rare variants are included in the table.
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 | 31 | 32 | ||||
| missense | 40 | 46 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 4 | 0 | 41 | 33 | 1 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- loftool
- 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