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UniProtKB/Swiss-Prot O60931: Variant p.Asn288Lys

Cystinosin
Gene: CTNS
Variant information

Variant position:  288
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 Asparagine (N) to Lysine (K) at position 288 (N288K, p.Asn288Lys).
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 polar (N) to large size and basic (K)
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 CTNS; abolished cystine transport.
Any additional useful information about the variant.



Sequence information

Variant position:  288
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  367
The length of the canonical sequence.

Location on the sequence:   CFSYIKLAVTLVKYFPQAYM  N FYYKSTEGWSIGNVLLDFTG
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                         CFSYIKLAVTLVKYFPQAYMNFYYKSTEGWSIGNVLLDFTG

Mouse                         CFSYIKLIITLIKYFPQAYMNFYYKSTKGWSIGGVLLDFTG

Bovine                        CFSYIKLAVTLVKYFPQAYMNFHYKSTEGWSIGNVLLDFTG

Caenorhabditis elegans        SLSYIKMAVTCCKYFPQAYFNYTRKSTVGWSIGNIMLDFTG

Drosophila                    YCSYVKLTITIIKYVPQALMNYRRKSTSGWSIGNILLDFTG

Slime mold                    YYSYVKLFITFIKYIPQAYLNFKNKSTSGWSVHNVLLDFSG

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 23 – 367 Cystinosin
Topological domain 283 – 297 Cytoplasmic
Domain 263 – 328 PQ-loop 2
Binding site 305 – 305 H(+); protonated following cystine-binding
Mutagenesis 270 – 270 S -> T. Gain-of-function mutant that shows higher transport of cystine.
Mutagenesis 274 – 274 L -> F. Gain-of-function mutant that shows higher transport of cystine.
Mutagenesis 280 – 288 Missing. In delta(A) mutant; abolished localization to the lysosome; when associated with deletion of 362-G--L-366.
Mutagenesis 281 – 281 Y -> F. Decreased midpoint potential. Accelerated the time course.
Mutagenesis 286 – 289 YMNF -> AAAA. In mu(b) mutant; does not abolish localization to the lysosome; when associated with deletion of 362-G--L-366.
Mutagenesis 305 – 305 D -> E. Abolished steady-state transport current.
Mutagenesis 305 – 305 D -> N. Abolished transient cxurrents. Abolished steady-state transport current.


Literature citations

Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.
Kalatzis V.; Cohen-Solal L.; Cordier B.; Frishberg Y.; Kemper M.; Nuutinen E.M.; Legrand E.; Cochat P.; Antignac C.;
Hum. Mutat. 20:439-446(2002)
Cited for: VARIANTS CTNS VAL-110; ARG-222; LYS-288; ASP-346--349-PHE DEL AND ASP-VAL-GLU-PHE-349 INS; VARIANTS CTNSJAN THR-177 AND LEU-200;

Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin.
Kalatzis V.; Nevo N.; Cherqui S.; Gasnier B.; Antignac C.;
Hum. Mol. Genet. 13:1361-1371(2004)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS CTNS VAL-110; PHE-133; PHE-139; PHE-141; PRO-158; ASP-169; SER-177; ARG-182; ASN-205; ASP-205 DEL; ARG-222; SER-270 DEL; LYS-288; ASN-298; TYR-305; ARG-308; PRO-338; ARG-339; 343-ILE--ASP-346 DEL; ASP-346--349-PHE DEL AND ASP-VAL-GLU-PHE-349 INS; CHARACTERIZATION OF VARIANT CTNSJAN 67-ILE--PRO-73 DEL; PRO-CYS-SER-154 INS; LEU-200; ARG-280; LYS-323 AND ASN-346; CHARACTERIZATION OF VARIANT CTNSANN ARG-197; CHARACTERIZATION OF VARIANT ILE-42 AND ILE-260;

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.