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UniProtKB/Swiss-Prot P78504: Variant p.Cys234Tyr

Protein jagged-1
Gene: JAG1
Variant information

Variant position:  234
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 234 (C234Y, p.Cys234Tyr).
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:  Deafness, congenital heart defects, and posterior embryotoxon (DCHE) [MIM:617992]: An autosomal dominant disease characterized by mild to severe combined hearing loss, congenital heart defects, and posterior embryotoxon, a corneal abnormality consisting of a central collagen core surrounded by a thin layer of Descemets membrane and separated from the anterior chamber by a layer of endothelium. Congenital heart defects include tetralogy of Fallot, ventricular septal defect, or isolated peripheral pulmonic stenosis. {ECO:0000269|PubMed:12022040, ECO:0000269|PubMed:20437614}. 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 DCHE; the mutant is unable to activate Notch signaling.
Any additional useful information about the variant.

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



Sequence information

Variant position:  234
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1218
The length of the canonical sequence.

Location on the sequence:   QNGNKTCMEGWMGPECNRAI  C RQGCSPKHGSCKLPGDCRCQ
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                         QNGNKTCMEGWMGPECNRAICRQGCSPKHGSCKLPGDCRCQ

Mouse                         QNGNKTCMEGWMGPDCNKAICRQGCSPKHGSCKLPGDCRCQ

Rat                           QNGNKTCMEGWMGPECNKAICRQGCSPKHGSCKLPGDCRCQ

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 34 – 1218 Protein jagged-1
Topological domain 34 – 1067 Extracellular
Domain 230 – 263 EGF-like 1
Glycosylation 217 – 217 N-linked (GlcNAc...) asparagine
Disulfide bond 234 – 245


Literature citations

Familial deafness, congenital heart defects, and posterior embryotoxon caused by cysteine substitution in the first epidermal-growth-factor-like domain of Jagged 1.
Le Caignec C.; Lefevre M.; Schott J.J.; Chaventre A.; Gayet M.; Calais C.; Moisan J.P.;
Am. J. Hum. Genet. 71:180-186(2002)
Cited for: INVOLVEMENT IN DCHE; VARIANT DCHE TYR-234;

Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis.
Bauer R.C.; Laney A.O.; Smith R.; Gerfen J.; Morrissette J.J.; Woyciechowski S.; Garbarini J.; Loomes K.M.; Krantz I.D.; Urban Z.; Gelb B.D.; Goldmuntz E.; Spinner N.B.;
Hum. Mutat. 31:594-601(2010)
Cited for: VARIANTS SER-664; GLN-937 AND GLN-1104; CHARACTERIZATION OF VARIANTS SER-664 AND GLN-937; VARIANT TOF LEU-810; CHARACTERIZATION OF VARIANTS TOF ASP-274 AND LEU-810; CHARACTERIZATION OF VARIANT ALGS1 SER-37; CHARACTERIZATION OF VARIANT DCHE TYR-234; FUNCTION;

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.