UniProtKB/Swiss-Prot Q9HCJ1: Variant p.Leu244Ser

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 244 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Leucine (L) to Serine (S) at position 244 (L244S, p.Leu244Ser). 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 hydrophobic (L) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -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: Found in individuals of a consanguinous family with intellectual disability syndrome, deafness and ankylosis; likely pathogenic; localizes at the plasma membrane; loss-of-function. Any additional useful information about the variant.

Sequence information

Variant position: 244 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 492 The length of the canonical sequence.
Location on the sequence: SGPELGGDATIRKMLSFWWP L ALILATQRISRPIVNLFVSR 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.
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.

Type	Positions	Description
Chain	1 – 492	Mineralization regulator ANKH
Topological domain	211 – 326	Cytoplasmic

Literature citations

The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP.
Szeri F.; Lundkvist S.; Donnelly S.; Engelke U.F.H.; Rhee K.; Williams C.J.; Sundberg J.P.; Wevers R.A.; Tomlinson R.E.; Jansen R.S.; van de Wetering K.;
PLoS Genet. 16:e1008884-e1008884(2020)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; CHARACTERIZATION OF VARIANT SER-244; The Mineralization Regulator ANKH Mediates Cellular Efflux of ATP, Not Pyrophosphate.
Szeri F.; Niaziorimi F.; Donnelly S.; Fariha N.; Tertyshnaia M.; Patel D.; Lundkvist S.; van de Wetering K.;
J. Bone Miner. Res. 37:1024-1031(2022)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; CHARACTERIZATION OF VARIANT SER-244; Autosomal recessive mental retardation, deafness, ankylosis, and mild hypophosphatemia associated with a novel ANKH mutation in a consanguineous family.
Morava E.; Kuehnisch J.; Drijvers J.M.; Robben J.H.; Cremers C.; van Setten P.; Branten A.; Stumpp S.; de Jong A.; Voesenek K.; Vermeer S.; Heister A.; Claahsen-van der Grinten H.L.; O'Neill C.W.; Willemsen M.A.; Lefeber D.; Deen P.M.; Kornak U.; Kremer H.; Wevers R.A.;
J. Clin. Endocrinol. Metab. 96:E189-E198(2011)
Cited for: VARIANT SER-244; CHARACTERIZATION OF VARIANT SER-244; FUNCTION; SUBCELLULAR LOCATION;