UniProtKB/Swiss-Prot Q92643: Variant p.Leu86Pro

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

86 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 Leucine (L) to Proline (P) at position 86 (L86P, p.Leu86Pro). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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 NEDHCAS; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

86 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:

LSVYRSVKRLGIPDSHIVLM L ADDMACNPRNPKPATVFSHK 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                         LSVYRSVKRLGIPDSHIVLMLADDMACNPRNPKPATVFSHK

Mouse                         LSVYRSVKRLGIPDSHIVLMLADDMACNARNPKPATVFSHK

Pig                           LSVYRSVKRLGIPDSHIVLMLADDMACNPRNPKPATVYSHK

Bovine                        LSVYRSVKRLGIPDSHIVLMLADDMACNPRNPKPATVYSHK

Caenorhabditis elegans        LALYHSIKRLGIPDSNIIMMLAEDVPCNSRNPRPGTVYAAR

Drosophila                    LSIYRSVKRLGIPDSQIILMIADDMACNARNPRPGQVYNNA

Baker's yeast                 LSMYRTVKRLGIPDSQIILMLSDDVACNSRNLFPGSVFNNK

Fission yeast                 LGIYRSVKRLGIPDSQIILMIADDYACNSRNLFPGTVFDNA

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
Binding site	79 – 79
Binding site	82 – 82
Disulfide bond	92 – 92	Interchain (with C-182 in PIGT)
Alternative sequence	50 – 125	Missing. In isoform 2.
Mutagenesis	74 – 74	R -> A. No effect on function in GPI-anchor attachment to protein.
Mutagenesis	79 – 79	D -> A. No effect on function in GPI-anchor attachment to protein.
Mutagenesis	92 – 92	C -> A. Decreased function in GPI-anchor attachment to protein. Decreases GPI-anchor transamidase activity by approximately 40%.
Mutagenesis	92 – 92	C -> S. Decreased function in GPI-anchor attachment to protein.
Beta strand	82 – 88

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.