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UniProtKB/Swiss-Prot Q8TB36: Variant p.Arg120Gln

Ganglioside-induced differentiation-associated protein 1
Gene: GDAP1
Chromosomal location: 8q13.3
Variant information

Variant position:  120
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 120 (R120Q, p.Arg120Gln).
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 large size and basic (R) to medium size and polar (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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 4A (CMT4A) [MIM:214400]: A recessive demyelinating 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). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4A is a severe form characterized by early age of onset and rapid progression leading to inability to walk in late childhood or adolescence. {ECO:0000269|PubMed:11743579, ECO:0000269|PubMed:12601710, ECO:0000269|PubMed:15772096, ECO:0000269|PubMed:16172208}. 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 CMT4A; no effect on mitochondrial localization but impairment in the ability to induce mitochondrial fragmentation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  120
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  358
The length of the canonical sequence.

Location on the sequence:   TFLDERTPRLMPDKESMYYP  R VQHYRELLDSLPMDAYTHGC
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                         TFLDERTPRLMPDKESMYYPRVQHYRELLDSLPMDAYTHGC

Mouse                         TFLDERTPRLMPDEGSMYYPRVQHYRELLDSLPMDAYTHGC

Bovine                        TFLDEKTPRLMPDKGSMYYPRVQHYRELLDSLPMDAYTHGC

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 – 358 Ganglioside-induced differentiation-associated protein 1
Mutagenesis 116 – 116 M -> H. Impairment in the ability to induce mitochondrial fragmentation.


Literature citations

GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is expressed in neurons and is associated with mitochondria.
Pedrola L.; Espert A.; Wu X.; Claramunt R.; Shy M.E.; Palau F.;
Hum. Mol. Genet. 14:1087-1094(2005)
Cited for: SUBCELLULAR LOCATION; MUTAGENESIS OF THR-157; CHARACTERIZATION OF VARIANTS CMT4A GLN-120 AND HIS-161; CHARACTERIZATION OF VARIANT CMTRIA CYS-282; CHARACTERIZATION OF VARIANT CMT2K TRP-120;

Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease.
Niemann A.; Ruegg M.; La Padula V.; Schenone A.; Suter U.;
J. Cell Biol. 170:1067-1078(2005)
Cited for: TISSUE SPECIFICITY; SUBCELLULAR LOCATION; TOPOLOGY; FUNCTION; MUTAGENESIS OF MET-116; CHARACTERIZATION OF VARIANTS CMT4A GLN-120 AND HIS-161; CHARACTERIZATION OF VARIANT CMT2RV GLN-310; CHARACTERIZATION OF VARIANT CMTRIA CYS-282;

CMT4A: identification of a Hispanic GDAP1 founder mutation.
Boerkoel C.F.; Takashima H.; Nakagawa M.; Izumo S.; Armstrong D.; Butler I.; Mancias P.; Papasozomenos S.C.H.; Stern L.Z.; Lupski J.R.;
Ann. Neurol. 53:400-405(2003)
Cited for: VARIANT CMT4A GLN-120;

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.