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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NQW8: Variant p.Ser435Phe

Cyclic nucleotide-gated channel beta-3
Gene: CNGB3
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Variant information Variant position: help 435 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Serine (S) to Phenylalanine (F) at position 435 (S435F, p.Ser435Phe). 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: help Change from small size and polar (S) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In ACHM3; does not affect channel assembly but significantly decreases trafficking to the cell membrane; results in increased affinity for cAMP and cGMP and reduced steady state channel rectification; increases channel open probability but decreases channel conductance; modulates selectivity toward monovalent ions, with relative permeability for Na(+) > K(+) > Rb(+) > Li(+) > Cs(+); increases sensitivity to L-cis diltiazem. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 435 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 809 The length of the canonical sequence.
Location on the sequence: help QTLFEIVFQLLNFFSGVFVF S SLIGQMRDVIGAATANQNYF 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         QTLFEIVFQLLNFFSGVFVFSSLIGQMRDVIGAATANQNYF

                              QTSFEIVFQLLNFFSGVFVFSSLIGQMQDVIGAATANQNNF

Mouse                         QTSFEIVFQFLNFFSGVFVFSSLIGQMRDVIGAATANQNYF
Sequence annotation in neighborhood: help 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 1 – 809 Cyclic nucleotide-gated channel beta-3
Transmembrane 421 – 445 Helical; Name=S6
Region 348 – 447 Ion conduction pathway
Site 434 – 434 Central gate
Site 438 – 438 Central gate
Site 442 – 442 Occludes the pore below the central gate
Helix 417 – 448



Literature citations
Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8Q21.
Kohl S.; Baumann B.; Broghammer M.; Jaegle H.; Sieving P.; Kellner U.; Spegal R.; Anastasi M.; Zrenner E.; Sharpe L.T.; Wissinger B.;
Hum. Mol. Genet. 9:2107-2116(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); TISSUE SPECIFICITY; VARIANT ACHM3 PHE-435; VARIANTS TRP-234; PRO-298 AND GLY-755; Genetic basis of total colourblindness among the Pingelapese islanders.
Sundin O.H.; Yang J.-M.; Li Y.; Zhu D.; Hurd J.N.; Mitchell T.N.; Silva E.D.; Maumenee I.H.;
Nat. Genet. 25:289-293(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 114-809 (ISOFORM 2); FUNCTION; SUBUNIT; VARIANT ACHM3 PHE-435; Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels.
Peng C.; Rich E.D.; Varnum M.D.;
J. Biol. Chem. 278:34533-34540(2003)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; CHARACTERIZATION OF VARIANT ACHM3 PHE-435; CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.
Kohl S.; Varsanyi B.; Antunes G.A.; Baumann B.; Hoyng C.B.; Jaegle H.; Rosenberg T.; Kellner U.; Lorenz B.; Salati R.; Jurklies B.; Farkas A.; Andreasson S.; Weleber R.G.; Jacobson S.G.; Rudolph G.; Castellan C.; Dollfus H.; Legius E.; Anastasi M.; Bitoun P.; Lev D.; Sieving P.A.; Munier F.L.; Zrenner E.; Sharpe L.T.; Cremers F.P.M.; Wissinger B.;
Eur. J. Hum. Genet. 13:302-308(2005)
Cited for: VARIANTS ACHM3 PHE-156; LEU-309; PHE-435 AND 720-GLN--LYS-726 DEL;
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.