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UniProtKB/Swiss-Prot O60931: Variant p.Asp346Asn

Cystinosin
Gene: CTNS
Variant information

Variant position:  346
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 Aspartate (D) to Asparagine (N) at position 346 (D346N, p.Asp346Asn).
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 acidic (D) to medium size and polar (N)
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 CTNS; atypical; slightly decreased cystine transport.
Any additional useful information about the variant.

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



Sequence information

Variant position:  346
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:   WTLIFGDPTKFGLGVFSIVF  D VVFFIQHFCLYRKRPGYDQL
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                         WTLIFGDPTKFGLGVFSIVFDVVFFIQHFCLYR--KRP-----GYDQL

Mouse                         WTLIFGDPTKFGLGVFTIFFDVVFFIQHFYLYR--KKP---

Bovine                        WTLIFGDPTKFGLGIFSIIFDVVFFIQHFCLYR--KKP---

Caenorhabditis elegans        WSAFYANPVKFGLGFVSIFFDIIFMVQHYVLYPNAEVPHNE

Drosophila                    WVSIFGDPTKFGLGLFSVLFDVFFMLQHYVFYRHSRES---

Slime mold                    WNIFTGDPVKLGLSLFSIAFDILFIIQHYILYRNPKSK---

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
Transmembrane 336 – 356 Helical
Mutagenesis 335 – 335 K -> Q. Abolished steady-state transport current. Decreased midpoint potential. Impaired dielectric distance. Accelerated the time course.
Mutagenesis 362 – 362 G -> A. Does not affect localization to the lysosome.
Mutagenesis 363 – 363 Y -> A. Strongly reduced but not abolished localization to the lysosome, leading to partial relocation to the cell membrane.
Mutagenesis 364 – 364 D -> A. Does not affect localization to the lysosome.
Mutagenesis 365 – 365 Q -> A. Does not affect localization to the lysosome.
Mutagenesis 366 – 366 L -> A. Strongly reduced but not abolished localization to the lysosome, leading to partial relocation to the cell membrane.


Literature citations

Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.
Attard M.; Jean G.; Forestier L.; Cherqui S.; van 't Hoff W.; Broyer M.; Antignac C.; Town M.;
Hum. Mol. Genet. 8:2507-2514(1999)
Cited for: VARIANTS CTNS PHE-139; ASP-205 DEL; SER-270 DEL; TYR-305; ARG-308; PRO-338; ARG-339; 343-ILE--ASP-346 DEL AND ASN-346; VARIANT ILE-42; VARIANT CTNSJAN PRO-CYS-SER-154 INS;

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.