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UniProtKB/Swiss-Prot P04629: Variant p.Asp596Asn

High affinity nerve growth factor receptor
Gene: NTRK1
Variant information

Variant position:  596
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 Aspartate (D) to Asparagine (N) at position 596 (D596N, p.Asp596Asn).
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 acidic (D) to medium size and polar (N)
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:  Congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]: Characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II. {ECO:0000269|PubMed:10090906, ECO:0000269|PubMed:10233776, ECO:0000269|PubMed:10330344, ECO:0000269|PubMed:10567924, ECO:0000269|PubMed:10861667, ECO:0000269|PubMed:10982191, ECO:0000269|PubMed:11159935, ECO:0000269|PubMed:11310631, ECO:0000269|PubMed:18077166, ECO:0000269|PubMed:22302274, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:28177573, ECO:0000269|PubMed:28328124, ECO:0000269|PubMed:8696348}. 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 CIPA; abolishes autophosphorylation.
Any additional useful information about the variant.



Sequence information

Variant position:  596
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:   FGVCTEGRPLLMVFEYMRHG  D LNRFLRSHGPDAKLLAGGED
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                         FGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGED

Mouse                         FGVCTEGGPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGED

Rat                           FGVCTEGGPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGED

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 33 – 796 High affinity nerve growth factor receptor
Topological domain 440 – 796 Cytoplasmic
Domain 510 – 781 Protein kinase


Literature citations

Novel NTRK1 mutations associated with congenital insensitivity to pain with anhidrosis verified by functional studies.
Nam T.S.; Li W.; Yoon S.; Eom G.H.; Kim M.K.; Jung S.T.; Choi S.Y.;
J. Peripher. Nerv. Syst. 22:92-99(2017)
Cited for: PHOSPHORYLATION; VARIANTS CIPA 235-SER--GLY-796 DEL; ASN-596 AND TYR-674; CHARACTERIZATION OF VARIANTS CIPA 235-SER--GLY-796 DEL AND ASN-596;

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.