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UniProtKB/Swiss-Prot Q9HAN9: Variant p.Glu257Lys

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
Gene: NMNAT1
Variant information

Variant position:  257
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Glutamate (E) to Lysine (K) at position 257 (E257K, p.Glu257Lys).
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 (E) to large size and basic (K)
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

Variant description:  In LCA9; results in significantly reduced enzymatic activity; the mutant localizes to the cytoplasm.
Any additional useful information about the variant.

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

Sequence information

Variant position:  257
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  279
The length of the canonical sequence.

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.




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.

Chain 1 – 279 Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
Helix 256 – 259

Literature citations

Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration.
Koenekoop R.K.; Wang H.; Majewski J.; Wang X.; Lopez I.; Ren H.; Chen Y.; Li Y.; Fishman G.A.; Genead M.; Schwartzentruber J.; Solanki N.; Traboulsi E.I.; Cheng J.; Logan C.V.; McKibbin M.; Hayward B.E.; Parry D.A.; Johnson C.A.; Nageeb M.; Poulter J.A.; Mohamed M.D.; Jafri H.; Rashid Y.; Taylor G.R.; Keser V.; Mardon G.; Xu H.; Inglehearn C.F.; Fu Q.; Toomes C.; Chen R.;
Nat. Genet. 44:1035-1039(2012)

Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis.
Chiang P.W.; Wang J.; Chen Y.; Fu Q.; Zhong J.; Chen Y.; Yi X.; Wu R.; Gan H.; Shi Y.; Chen Y.; Barnett C.; Wheaton D.; Day M.; Sutherland J.; Heon E.; Weleber R.G.; Gabriel L.A.; Cong P.; Chuang K.; Ye S.; Sallum J.M.; Qi M.;
Nat. Genet. 44:972-974(2012)
Cited for: VARIANTS LCA9 THR-35; GLY-98; PHE-151; VAL-153; LYS-257 AND ASP-273;

NMNAT1 mutations cause Leber congenital amaurosis.
Falk M.J.; Zhang Q.; Nakamaru-Ogiso E.; Kannabiran C.; Fonseca-Kelly Z.; Chakarova C.; Audo I.; Mackay D.S.; Zeitz C.; Borman A.D.; Staniszewska M.; Shukla R.; Palavalli L.; Mohand-Said S.; Waseem N.H.; Jalali S.; Perin J.C.; Place E.; Ostrovsky J.; Xiao R.; Bhattacharya S.S.; Consugar M.; Webster A.R.; Sahel J.A.; Moore A.T.; Berson E.L.; Liu Q.; Gai X.; Pierce E.A.;
Nat. Genet. 44:1040-1045(2012)
Cited for: VARIANTS LCA9 MET-9; THR-13; ASN-20; GLY-33; VAL-54; TRP-66; VAL-69; HIS-72; GLY-98; ARG-156; MET-184; CYS-237 AND LYS-257; CHARACTERIZATION OF VARIANTS LCA9 MET-9; TRP-66 AND CYS-237;

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.