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UniProtKB/Swiss-Prot O60931: Variant p.Asn323Lys

Cystinosin
Gene: CTNS
Variant information

Variant position:  323
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 323 (N323K, p.Asn323Lys).
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 CTNSJAN; abolished cystine transport.
Any additional useful information about the variant.

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



Sequence information

Variant position:  323
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:   LLDFTGGSFSLLQMFLQSYN  N DQWTLIFGDPTKFGLGVFSI
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                         LLDFTGGSFSLLQMFLQSYNNDQWTLIFGDPTKFGLGVFSI

Mouse                         LLDFTGGSFSLLQMFLQSYNNDQWTLIFGDPTKFGLGVFTI

Bovine                        LLDFTGGSFSLLQMFLQSYNNDQWTLIFGDPTKFGLGIFSI

Caenorhabditis elegans        MLDFTGGTLDILQMILQAVNVNDWSAFYANPVKFGLGFVSI

Drosophila                    LLDFTGGTLSMLQMILNAHNYDDWVSIFGDPTKFGLGLFSV

Slime mold                    LLDFSGGVLSLLQMFLDVADSGNWNIFTGDPVKLGLSLFSI

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 319 – 335 Lumenal
Domain 263 – 328 PQ-loop 2
Binding site 305 – 305 H(+); protonated following cystine-binding
Mutagenesis 305 – 305 D -> E. Abolished steady-state transport current.
Mutagenesis 305 – 305 D -> N. Abolished transient cxurrents. Abolished steady-state transport current.
Mutagenesis 309 – 309 G -> CS. Gain-of-function mutant that shows higher transport of cystine.
Mutagenesis 312 – 312 S -> N. Gain-of-function mutant that shows higher transport of cystine.
Mutagenesis 335 – 335 K -> Q. Abolished steady-state transport current. Decreased midpoint potential. Impaired dielectric distance. Accelerated the time course.


Literature citations

Mutations of CTNS causing intermediate cystinosis.
Thoene J.; Lemons R.; Anikster Y.; Mullet J.; Paelicke K.; Lucero C.; Gahl W.A.; Schneider J.; Shu S.G.; Campbell H.T.;
Mol. Genet. Metab. 67:283-293(1999)
Cited for: VARIANTS CTNSJAN ARG-280 AND LYS-323;

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;

Two novel CTNS mutations in cystinosis patients in Thailand.
Yeetong P.; Tongkobpetch S.; Kingwatanakul P.; Deekajorndech T.; Bernardini I.M.; Suphapeetiporn K.; Gahl W.A.; Shotelersuk V.;
Gene 499:323-325(2012)
Cited for: VARIANTS CTNS ASP-309 AND LYS-323;

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.