RAB7A

Chr 3AD

RAB7A, member RAS oncogene family

Also known as: CMT2B, PRO2706, RAB7

NCBI Gene: 7879ENSG00000075785UniProt: P51149

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. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 2BMIM #600882
AD
229
ClinVar variants
17
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RAB7A
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease type 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 92 VUS of 229 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.969
Z-score 3.04
OE 0.00 (0.00–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.28Z-score
OE missense 0.40 (0.32–0.51)
46 obs / 114.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.40 (0.32–0.51)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 0 / 10.8Missense obs/exp: 46 / 114.7Syn Z: 0.30

ClinVar Variant Classifications

229 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS92
Likely Benign86
Benign24
Conflicting10
16
Pathogenic
1
Likely Pathogenic
92
VUS
86
Likely Benign
24
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
12
0
16
Likely Pathogenic
0
0
1
0
1
VUS
4
44
44
0
92
Likely Benign
0
1
51
34
86
Benign
0
0
23
1
24
Conflicting
—10
Total44913135229

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RAB7A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, type 2B

MIM #600882

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — RAB7A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
USP4 depletion-driven RAB7A ubiquitylation impairs autophagosome-lysosome fusion and aggravates periodontitis.
Kang S et al.·Autophagy
2025
EGFR tyrosine kinase activity and Rab GTPases coordinate EGFR trafficking to regulate macrophage activation in sepsis.
Zhang X et al.·Cell Death Dis
2022
Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.
Matsuda J et al.·Autophagy
2020
TSPAN1 promotes autophagy flux and mediates cooperation between WNT-CTNNB1 signaling and autophagy via the MIR454-FAM83A-TSPAN1 axis in pancreatic cancer.
Zhou C et al.·Autophagy
2021
Lactate accumulation drives hepatocellular carcinoma metastasis through facilitating tumor-derived exosome biogenesis by Rab7A lactylation.
Jiang C et al.·Cancer Lett
2025
Targeting autophagy in HCC treatment: exploiting the CD147 internalization pathway.
Qian M et al.·Cell Commun Signal
2024
Investigating the impact of Ras-related protein RAB7A on colon adenocarcinoma behavior and its clinical significance.
Shan Z et al.·Biofactors
2025
High RAS-related protein Rab-7a (RAB7A) expression is a poor prognostic factor in pancreatic adenocarcinoma.
Liu Q et al.·Sci Rep
2022
CLN3 regulates endosomal function by modulating Rab7A-effector interactions.
Yasa S et al.·J Cell Sci
2020
RAB7A GTPase Is Involved in Mitophagosome Formation and Autophagosome-Lysosome Fusion in N2a Cells Treated with the Prion Protein Fragment 106-126.
Li Z et al.·Mol Neurobiol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Exosomal microRNA-448 suppresses the malignant behaviors of liver cancer cells by targeting RAB7A and inhibiting glycolysis.
Chen Y et al.·Oncol Lett
2026🔓 Open Access
Songorine inhibits mitophagy in chronic heart failure via the TBC1D15/Fis1/Rab7A pathway.
Liu W et al.·Br J Pharmacol
2025
Abnormal fat distribution in two patients with RAB7A-associated Charcot-Marie-Tooth type 2B: a case report.
Kodal LS et al.·BMC Neurol
2025🔓 Open AccessCohort
Rab7a is required to degrade select blood-brain barrier junctional proteins after ischemic stroke.
Cottarelli A et al.·Acta Neuropathol Commun
2025🔓 Open Access
The hereditary spastic paraplegia type 21 (SPG21) protein is a RAB7A effector that promotes noncanonical mTORC1-catalyzed TFEB phosphorylation and cytoplasmic retention.
Kunselman JM et al.·Mol Biol Cell
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools