Home  |  Contact

UniProtKB/Swiss-Prot P04629: Variant p.Arg6Trp

High affinity nerve growth factor receptor
Gene: NTRK1
Variant information

Variant position:  6
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Tryptophan (W) at position 6 (R6W, p.Arg6Trp).
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 large size and aromatic (W)
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

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



Sequence information

Variant position:  6
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  796
The length of the canonical sequence.

Location on the sequence:   MLRGG  R RGQLGWHSWAAGPGSLLAWL
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                         MLRGGRRGQLGWHSWAAGPGSLLAWL

Mouse                         MLRGQRLGQLGWHRPAAGLGSLMTSL

Rat                           MLRGQRHGQLGWHRPAAGLGGLVTSL

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
Signal peptide 1 – 32
Alternative sequence 1 – 71 MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTEL -> MKEAALICLAPSVPPILTVKSWDTMQLRAARSRCTNLLAAS. In isoform 3.


Literature citations

Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.
Mardy S.; Miura Y.; Endo F.; Matsuda I.; Sztriha L.; Frossard P.; Moosa A.; Ismail E.A.R.; Macaya A.; Andria G.; Toscano E.; Gibson W.; Graham G.E.; Indo Y.;
Am. J. Hum. Genet. 64:1570-1579(1999)
Cited for: VARIANTS CIPA PRO-213; TRP-649 AND SER-714; VARIANTS SER-85; TYR-604 AND VAL-613;

Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor.
Mardy S.; Miura Y.; Endo F.; Matsuda I.; Indo Y.;
Hum. Mol. Genet. 10:179-188(2001)
Cited for: CHARACTERIZATION OF VARIANTS CIPA PRO-93; PRO-213; ARG-522; ARG-577; TRP-649; CYS-654 AND SER-714; CHARACTERIZATION OF VARIANTS SER-85; TYR-604; VAL-613 AND TYR-674;

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.
Davidson G.L.; Murphy S.M.; Polke J.M.; Laura M.; Salih M.A.; Muntoni F.; Blake J.; Brandner S.; Davies N.; Horvath R.; Price S.; Donaghy M.; Roberts M.; Foulds N.; Ramdharry G.; Soler D.; Lunn M.P.; Manji H.; Davis M.B.; Houlden H.; Reilly M.M.;
J. Neurol. 259:1673-1685(2012)
Cited for: VARIANTS CIPA LYS-492 AND CYS-654; VARIANT TRP-6;

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.