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UniProtKB/Swiss-Prot Q92734: Variant p.Arg106Cys

Protein TFG
Gene: TFG
Variant information

Variant position:  106
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 Cysteine (C) at position 106 (R106C, p.Arg106Cys).
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 (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Spastic paraplegia 57, autosomal recessive (SPG57) [MIM:615658]: A complicated form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. {ECO:0000269|PubMed:23479643, ECO:0000269|PubMed:27492651, ECO:0000269|PubMed:27813252, ECO:0000269|PubMed:30237576}. 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 SPG57; defective self-assembly into an oligomeric complex; impaired interaction with PDCD6; causes mitochondrial fragmentation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  106
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  400
The length of the canonical sequence.

Location on the sequence:   LTLFVNGQPRPLESSQVKYL  R RELIELRNKVNRLLDSLEPP
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.

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 – 400 Protein TFG
Coiled coil 97 – 124


Literature citations

Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure.
Beetz C.; Johnson A.; Schuh A.L.; Thakur S.; Varga R.E.; Fothergill T.; Hertel N.; Bomba-Warczak E.; Thiele H.; Nurnberg G.; Altmuller J.; Saxena R.; Chapman E.R.; Dent E.W.; Nurnberg P.; Audhya A.;
Proc. Natl. Acad. Sci. U.S.A. 110:5091-5096(2013)
Cited for: FUNCTION; SUBUNIT; VARIANT SPG57 CYS-106; CHARACTERIZATION OF VARIANT SPG57 CYS-106;

The calcium-binding protein ALG-2 promotes endoplasmic reticulum exit site localization and polymerization of Trk-fused gene (TFG) protein.
Kanadome T.; Shibata H.; Kuwata K.; Takahara T.; Maki M.;
FEBS J. 284:56-76(2017)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH PDCD6; CHARACTERIZATION OF VARIANT SPG57 CYS-106; CHARACTERIZATION OF VARIANT HMSNO LEU-285;

Novel genetic, clinical, and pathomechanistic insights into TFG-associated hereditary spastic paraplegia.
Harlalka G.V.; McEntagart M.E.; Gupta N.; Skrzypiec A.E.; Mucha M.W.; Chioza B.A.; Simpson M.A.; Sreekantan-Nair A.; Pereira A.; Guenther S.; Jahic A.; Modarres H.; Moore-Barton H.; Trembath R.C.; Kabra M.; Baple E.L.; Thakur S.; Patton M.A.; Beetz C.; Pawlak R.; Crosby A.H.;
Hum. Mutat. 37:1157-1161(2016)
Cited for: VARIANTS SPG57 CYS-106 AND HIS-106; CHARACTERIZATION OF VARIANTS SPG57 CYS-106 AND HIS-106;

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.