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UniProtKB/Swiss-Prot Q16281: Variant p.Phe547Leu

Cyclic nucleotide-gated cation channel alpha-3
Gene: CNGA3
Variant information

Variant position:  547
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 Phenylalanine (F) to Leucine (L) at position 547 (F547L, p.Phe547Leu).
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 large size and aromatic (F) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration; a substantial reduction of macroscopic cGMP maximum current to only one-third of the mean value for wild-type CNGA3 + CNGB3 is observed for the mutant CNGA3 + CNGB3; is in large part located in the cell membrane at 37 and 27 degrees Celsius.
Any additional useful information about the variant.

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

Sequence information

Variant position:  547
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  694
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 – 694 Cyclic nucleotide-gated cation channel alpha-3
Topological domain 503 – 694 Cytoplasmic
Nucleotide binding 482 – 605 3',5'-cGMP
Binding site 549 – 549 3',5'-cGMP
Binding site 564 – 564 3',5'-cGMP

Literature citations

Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel.
Kohl S.; Marx T.; Giddings I.; Jaegle H.; Jacobson S.G.; Apfelstedt-Sylla E.; Zrenner E.; Sharpe L.T.; Wissinger B.;
Nat. Genet. 19:257-259(1998)
Cited for: VARIANTS ACHM2 LEU-163; GLN-283; TRP-283; ARG-291; TRP-410; MET-529; LEU-547 AND ARG-557; VARIANT MET-153;

CNGA3 mutations in hereditary cone photoreceptor disorders.
Wissinger B.; Gamer D.; Jaegle H.; Giorda R.; Marx T.; Mayer S.; Tippmann S.; Broghammer M.; Jurklies B.; Rosenberg T.; Jacobson S.G.; Sener E.C.; Tatlipinar S.; Hoyng C.B.; Castellan C.; Bitoun P.; Andreasson S.; Rudolph G.; Kellner U.; Lorenz B.; Wolff G.; Verellen-Dumoulin C.; Schwartz M.; Cremers F.P.M.; Apfelstedt-Sylla E.; Zrenner E.; Salati R.; Sharpe L.T.; Kohl S.;
Am. J. Hum. Genet. 69:722-737(2001)
Cited for: VARIANTS ACHM2 VAL-162; LEU-163; CYS-181; TYR-182; PHE-186; TYR-191; LYS-194; TRP-223; ARG-224; ASN-260; ASP-267; CYS-277; HIS-277; TRP-283; GLN-283; ARG-291; ILE-312 DEL; PRO-341; SER-369; SER-372; SER-380; THR-406; TRP-410; CYS-427; TRP-436; SER-471; VAL-485; SER-510; GLU-513; GLU-516; THR-522; ASP-525; MET-529; LEU-547; ARG-557; HIS-563; MET-565; HIS-569; CYS-573 AND LYS-593;

Achromatopsia caused by novel mutations in both CNGA3 and CNGB3.
Johnson S.; Michaelides M.; Aligianis I.A.; Ainsworth J.R.; Mollon J.D.; Maher E.R.; Moore A.T.; Hunt D.M.;
J. Med. Genet. 41:E20-E20(2004)
Cited for: VARIANTS ACHM2 TRP-223; TRP-436; LEU-547; ARG-548 AND HIS-569;

Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia.
Reuter P.; Koeppen K.; Ladewig T.; Kohl S.; Baumann B.; Wissinger B.;
Hum. Mutat. 29:1228-1236(2008)
Cited for: VARIANTS ACHM2 LYS-228; CYS-277; GLN-283; TRP-439; THR-469; LEU-547 AND ARG-557; CHARACTERIZATION OF VARIANTS ACHM2 LYS-228; GLN-283; ARG-291; TRP-439; THR-469; LEU-547; ARG-557 AND LYS-590;

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.