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UniProtKB/Swiss-Prot P46531: Variant p.Cys1496Tyr

Neurogenic locus notch homolog protein 1
Gene: NOTCH1
Chromosomal location: 9q34.3
Variant information

Variant position:  1496
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 Cysteine (C) to Tyrosine (Y) at position 1496 (C1496Y, p.Cys1496Tyr).
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 polar (C) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Adams-Oliver syndrome 5 (AOS5) [MIM:616028]: A form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. {ECO:0000269|PubMed:25132448}. 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 AOS5.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1496
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2555
The length of the canonical sequence.

Location on the sequence:   GGDCSLNFNDPWKNCTQSLQ  C WKYFSDGHCDSQCNSAGCLF
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                         GGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLF

Mouse                         GGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLF

Rat                           GGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLF

Xenopus laevis                GGDCSLNFNDPWKNCTQSLQCWKYFNDGKCDSQCNNTGCLY

Xenopus tropicalis            GGDCSLNFNDPWKNCTQSLQCWKYFNDGKCDSQCNNSGCLY

Zebrafish                     GGDCSLNFDDPWQNCSAALQCWRYFNDGKCDEQCATAGCLY

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 19 – 2555 Neurogenic locus notch homolog protein 1
Topological domain 19 – 1735 Extracellular
Repeat 1490 – 1531 LNR 2
Metal binding 1478 – 1478 Calcium 4
Glycosylation 1489 – 1489 N-linked (GlcNAc...) asparagine
Disulfide bond 1490 – 1514
Disulfide bond 1496 – 1509
Helix 1496 – 1498


Literature citations

Mutations in NOTCH1 cause Adams-Oliver syndrome.
Stittrich A.B.; Lehman A.; Bodian D.L.; Ashworth J.; Zong Z.; Li H.; Lam P.; Khromykh A.; Iyer R.K.; Vockley J.G.; Baveja R.; Silva E.S.; Dixon J.; Leon E.L.; Solomon B.D.; Glusman G.; Niederhuber J.E.; Roach J.C.; Patel M.S.;
Am. J. Hum. Genet. 95:275-284(2014)
Cited for: INVOLVEMENT IN AOS5; VARIANTS AOS5 ARG-429; TYR-1496 AND ASN-1989;

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.