UniProtKB/Swiss-Prot P51149: Variant p.Leu129Phe

Ras-related protein Rab-7a
Gene: RAB7A
Chromosomal location: 3q22.1
Variant information

Variant position:  129
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Leucine (L) to Phenylalanine (F) at position 129 (L129F, p.Leu129Phe).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and hydrophobic (L) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Charcot-Marie-Tooth disease 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. Nerve conduction velocities are normal or slightly reduced. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  129
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  207
The length of the canonical sequence.

Location on the sequence:   QASPRDPENFPFVVLGNKID  L ENRQVATKRAQAWCYSKNNI
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         QASPRDPENFPFVVLGNKIDLENRQVAT-KRAQAWCYSKNNI

Mouse                         QASPRDPENFPFVVLGNKIDLENRQVAT-KRAQAWCYSKNN

Rat                           QASPRDPENFPFVVLGNKIDLENRQVAT-KRAQAWCYSKNN

Bovine                        QASPRDPENFPFVVLGNKIDLENRQVAT-KRAQAWCYSKNN

Rabbit                        QASPRDPENFPFVVLGNKIDLENRQVAT-KRAQAWSYSKNN

Dog                           QASPRDPENFPFVVLGNKIDLENRQVAT-KRAQAWCYSKNN

Slime mold                    QAGPRDPDNFPFVVLGNKIDLENQRVVSQKRAASWCQSKGN

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 207 Ras-related protein Rab-7a


Literature citations

Disease mutations in Rab7 result in unregulated nucleotide exchange and inappropriate activation.
McCray B.A.; Skordalakes E.; Taylor J.P.;
Hum. Mol. Genet. 19:1033-1047(2010)
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF VARIANT CMT2B PHE-129 IN COMPLEX WITH GTP; CHARACTERIZATION OF VARIANTS CMT2B PHE-129 AND MET-162; FUNCTION; SUBUNIT; SUBCELLULAR LOCATION;

Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy.
Verhoeven K.; De Jonghe P.; Coen K.; Verpoorten N.; Auer-Grumbach M.; Kwon J.M.; FitzPatrick D.; Schmedding E.; De Vriendt E.; Jacobs A.; Van Gerwen V.; Wagner K.; Hartung H.-P.; Timmerman V.;
Am. J. Hum. Genet. 72:722-727(2003)
Cited for: VARIANTS CMT2B PHE-129 AND MET-162; TISSUE SPECIFICITY;

Rab7 mutants associated with Charcot-Marie-Tooth disease exhibit enhanced NGF-stimulated signaling.
Basuray S.; Mukherjee S.; Romero E.; Wilson M.C.; Wandinger-Ness A.;
PLoS ONE 5:E15351-E15351(2010)
Cited for: CHARACTERIZATION OF VARIANTS CMT2B PHE-129; ASN-157; THR-161 AND MET-162;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.