UniProtKB/Swiss-Prot Q92643: Variant p.Ala184Val

GPI-anchor transamidase
Gene: PIGK
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Variant information Variant position:

184 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Alanine (A) to Valine (V) at position 184 (A184V, p.Ala184Val). 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 small size and hydrophobic (A) to medium size and hydrophobic (V) 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 NEDHCAS; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs780683566 [ dbSNP | Ensembl ]

Sequence information Variant position:

184 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

395 The length of the canonical sequence.
Location on the sequence:

HGGNGFLKFQDSEEITNIEL A DAFEQMWQKRRYNELLFIID 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                         HGGNGFLKFQDSEEITNIELADAFEQMWQKRRYNELLFIID

Mouse                         HGGNGFLKFQDSEEITNIELADAFEQMWQKRRYNELLFIID

Pig                           HGGNGFLKFQDSEEITNIELADAFEQMWQKRRYNELLFIID

Bovine                        HGGNGFLKFQDSEEITNIELADAFEQMWQKRRYNELLFIID

Caenorhabditis elegans        HGGDSFMKFQDSEELTNVDLAYAIQTMFEDNRYHEMLVIAD

Drosophila                    HGGDGFLKFQDSEEITSQELADGIQQMWEKKRYNELFFMVD

Baker's yeast                 HGGDDFLKFQDAEEIASEDIADAFQQMYEKKRYNEIFFMID

Fission yeast                 HGGDGFIKFQDAEELSSEDLADAIEQIHQHKRYNEILFMVD

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	28 – 395	GPI-anchor transamidase
Topological domain	28 – 368	Lumenal
Active site	164 – 164	Proton donor
Mutagenesis	164 – 164	H -> A. Loss of function in GPI-anchor attachment to protein. Abolishes GPI-anchor transamidase activity.
Mutagenesis	174 – 174	D -> A. No effect on function in GPI-anchor attachment to protein.
Mutagenesis	198 – 198	E -> A. No effect on function in GPI-anchor attachment to protein.
Mutagenesis	204 – 204	D -> A. Decreased function in GPI-anchor attachment to protein.
Mutagenesis	204 – 204	D -> K. Reduces by 60% the GPI-anchor transamidase activity.
Helix	180 – 192

Literature citations
Bi-allelic variants in the GPI transamidase subunit PIGK cause a neurodevelopmental syndrome with hypotonia, cerebellar atrophy, and epilepsy.
Nguyen T.T.M.; Murakami Y.; Mobilio S.; Niceta M.; Zampino G.; Philippe C.; Moutton S.; Zaki M.S.; James K.N.; Musaev D.; Mu W.; Baranano K.; Nance J.R.; Rosenfeld J.A.; Braverman N.; Ciolfi A.; Millan F.; Person R.E.; Bruel A.L.; Thauvin-Robinet C.; Ververi A.; DeVile C.; Male A.; Efthymiou S.; Maroofian R.; Houlden H.; Maqbool S.; Rahman F.; Baratang N.V.; Rousseau J.; St-Denis A.; Elrick M.J.; Anselm I.; Rodan L.H.; Tartaglia M.; Gleeson J.; Kinoshita T.; Campeau P.M.;
Am. J. Hum. Genet. 106:484-495(2020)
Cited for: INVOLVEMENT IN NEDHCAS; VARIANTS NEDHCAS 33-GLN--PHE-395 DEL; PHE-53; PRO-86; VAL-87; ASN-88; SER-160; VAL-184; LYS-246 AND ARG-275;

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.