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UniProtKB/Swiss-Prot O95477: Variant p.Met1091Thr

Phospholipid-transporting ATPase ABCA1
Gene: ABCA1
Variant information

Variant position:  1091
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 Methionine (M) to Threonine (T) at position 1091 (M1091T, p.Met1091Thr).
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 hydrophobic (M) to medium size and polar (T)
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 FHA1; loss of localization to plasma membrane; decreased cholesterol efflux; decreased phospholipid efflux.
Any additional useful information about the variant.

Sequence information

Variant position:  1091
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2261
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.



Slime mold                    IF-----------------------IVGSIFQLVFSG----

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 – 2261 Phospholipid-transporting ATPase ABCA1
Domain 899 – 1131 ABC transporter 1
Lipidation 1110 – 1110 S-palmitoyl cysteine
Lipidation 1111 – 1111 S-palmitoyl cysteine
Mutagenesis 1110 – 1110 C -> S. Decreased palmitoylation; when associated with S-3, S-23 and S-1111.
Mutagenesis 1111 – 1111 C -> S. Decreased palmitoylation; when associated with S-3, S-23 and S-1110.

Literature citations

Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function.
Singaraja R.R.; Kang M.H.; Vaid K.; Sanders S.S.; Vilas G.L.; Arstikaitis P.; Coutinho J.; Drisdel R.C.; El-Husseini Ael D.; Green W.N.; Berthiaume L.; Hayden M.R.;
Circ. Res. 105:138-147(2009)

Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux.
Marcil M.; Brooks-Wilson A.; Clee S.M.; Roomp K.; Zhang L.-H.; Yu L.; Collins J.A.; van Dam M.; Molhuizen H.O.F.; Loubser O.; Ouellette B.F.F.; Sensen C.W.; Fichter K.; Mott S.; Denis M.; Boucher B.; Pimstone S.; Genest J. Jr.; Kastelein J.J.P.; Hayden M.R.;
Lancet 354:1341-1346(1999)
Cited for: VARIANTS FHA1 THR-1091 AND 1893-GLU-ASP-1894 DEL; FUNCTION;

Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes.
Clee S.M.; Kastelein J.J.P.; van Dam M.; Marcil M.; Roomp K.; Zwarts K.Y.; Collins J.A.; Roelants R.; Tamasawa N.; Stulc T.; Suda T.; Ceska R.; Boucher B.; Rondeau C.; DeSouich C.; Brooks-Wilson A.; Molhuizen H.O.F.; Frohlich J.; Genest J. Jr.; Hayden M.R.;
J. Clin. Invest. 106:1263-1270(2000)
Cited for: VARIANTS TGD ARG-597; ILE-929 AND ARG-1477; VARIANTS FHA1 LEU-693 DEL; THR-1091; 1893-GLU-ASP-1894 DEL AND LEU-2150;

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.