RAB7A

Chr 3

RAB7A, member RAS oncogene family

Also known as: CMT2B, PRO2706, RAB7

NCBI Gene: 7879 ENSG00000075785 UniProt: P51149

The RAB7A protein is a small GTPase that regulates vesicular trafficking in late endosomes and endosome-to-lysosome transport, playing essential roles in neurotrophin signaling and axonal transport. Mutations cause Charcot-Marie-Tooth disease type 2B, an autosomal dominant peripheral neuropathy. This gene is highly constrained against loss-of-function variation, reflecting its critical cellular functions.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCharcot-Marie-Tooth disease, axonal, type 2B

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Charcot-Marie-Tooth disease type 2 · AD · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in RAB7A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

162 rare PASS variants

Rare truncating (LoF)

1 in 5,900

16 rare PASS variants

Rare synonymous (reference)

1 in 310

117 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAB7A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 280	1 in 7,000
South Asian	~43k	1 in 670	1 in 780
Remaining (unassigned)	~30k	1 in 440	none seen
European (Finnish)	~27k	1 in 850	none seen
Admixed American	~22k	1 in 840	≈ 1 in 22,000
African / African American	~21k	1 in 460	≈ 1 in 6,800
East Asian	~20k	1 in 340	≈ 1 in 9,900
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓