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UniProtKB/Swiss-Prot P78504: Variant p.Gly274Asp

Protein jagged-1
Gene: JAG1
Variant information

Variant position:  274
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 Glycine (G) to Aspartate (D) at position 274 (G274D, p.Gly274Asp).
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 glycine (G) to medium size and acidic (D)
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:  Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. {ECO:0000269|PubMed:11152664, 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 TOF; temperature sensitive mutation; the protein is abnormally glycosylated and retained intracellularly; 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:  274
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:   QYGWQGLYCDKCIPHPGCVH  G ICNEPWQCLCETNWGGQLCD
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                         QYGWQGLYCDKCIPHPGCVHGICNEPWQCLCETNWGGQLCD

Mouse                         QYGWQGLYCDKCIPHPGCVHGTCNEPWQCLCETNWGGQLCD

Rat                           QYGWQGLYCDKCIPHPGCVHGTCNEPWQCLCETNWGGQLCD

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 264 – 294 EGF-like 2; atypical
Disulfide bond 265 – 276
Disulfide bond 271 – 282
Beta strand 273 – 275


Literature citations

Familial tetralogy of Fallot caused by mutation in the Jagged1 gene.
Eldadah Z.A.; Hamosh A.; Biery N.J.; Montgomery R.A.; Duke M.; Elkins R.; Dietz H.C.;
Hum. Mol. Genet. 10:163-169(2001)
Cited for: VARIANT TOF ASP-274;

Conditional JAG1 mutation shows the developing heart is more sensitive than developing liver to JAG1 dosage.
Lu F.; Morrissette J.J.D.; Spinner N.B.;
Am. J. Hum. Genet. 72:1065-1070(2003)
Cited for: CHARACTERIZATION OF VARIANT ASP-274;

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.