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UniProtKB/Swiss-Prot Q3LXA3: Variant p.Arg543Ile

Triokinase/FMN cyclase
Gene: TKFC
Variant information

Variant position:  543
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 Arginine (R) to Isoleucine (I) at position 543 (R543I, p.Arg543Ile).
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 basic (R) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 TKFCD; reduced protein levels in patient cells; very severe decrease of triokinase and glycerone kinase activities.
Any additional useful information about the variant.

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



Sequence information

Variant position:  543
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  575
The length of the canonical sequence.

Location on the sequence:   AVKSAEAAAEATKNMEAGAG  R ASYISSARLEQPDPGAVAAA
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                         A-VKSAEAAAEATKNMEAGAGRASYISSARLEQPDPGAVAAA

Mouse                         A-VKSAEAAAEATKNMEAGAGRASYISSAQLDQPDPGAVAA

Rat                           A-VKSAEAAAEATKNMEAGAGRASYISSAQLDQPDPGAVAA

Pig                           ALLENAEAAAEATKNMEAGAGRASYISSARLDQPDPGAVAA

Bovine                        A-VKSAEAAAEATKNMEAGAGRASYISSARLDQPDPGAVAA

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 1 – 575 Triokinase/FMN cyclase
Domain 372 – 571 DhaL
Modified residue 545 – 545 Phosphoserine
Alternative sequence 526 – 575 SAEAAAEATKNMEAGAGRASYISSARLEQPDPGAVAAAAILRAILEVLQS -> EGGGLVICP. In isoform 2.
Mutagenesis 556 – 556 D -> A. Abolishes both kinase and FMN cyclase activities.


Literature citations

Bi-allelic variants in TKFC encoding triokinase/FMN cyclase are associated with cataracts and multisystem disease.
Wortmann S.B.; Meunier B.; Mestek-Boukhibar L.; van den Broek F.; Maldonado E.M.; Clement E.; Weghuber D.; Spenger J.; Jaros Z.; Taha F.; Yue W.W.; Heales S.J.; Davison J.E.; Mayr J.A.; Rahman S.;
Am. J. Hum. Genet. 106:256-263(2020)
Cited for: INVOLVEMENT IN TKFCD; FUNCTION; CATALYTIC ACTIVITY; VARIANTS TKFCD SER-445 AND ILE-543; CHARACTERIZATION OF VARIANTS TKFCD SER-445 AND ILE-543;

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.