UniProtKB/SwissProt variant VAR

Variant information

Variant position:

145

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Asparagine (N) to Isoleucine (I) at position 145 (N145I, p.Asn145Ile).

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 polar (N) 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

Involvement in disease:

Non-ketotic hyperglycinemia (NKH) [MIM:605899]: Autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms. {ECO:0000269|PubMed:10873393, ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:16051266, ECO:0000269|PubMed:26371980, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:8005589, ECO:0000269|PubMed:9600239, ECO:0000269|PubMed:9621520}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In NKH; loss of aminomethyltransferase activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs386833682 [ dbSNP | Ensembl ]

Sequence information

Variant position:

145

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

Protein sequence length:

403

The length of the canonical sequence.

Location on the sequence:

GILDDLIVTNTSEGHLYVVS N AGCWEKDLALMQDKVRELQN

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                         GILDDLIVTNT-SEGHLYVVSNAGCWEKDLALMQDKVRELQ--N

                              GIEDDLIVTST-SEGYLYVVSNAGCWDKDLALMQGKVRELQ

Mouse                         GILDDLIVSNT-SEGHLYVVSNAGCRDKDLALMQDKVKEFQ

Bovine                        GILDDLIVTSA-SEGHLYVVSNAGCREKDLTLMQDKVRELQ

Chicken                       DIVDDLIVTNT-AEDHLYVVSNAGCADKDRAVMEGRAAELR

Slime mold                    GIIDDTMITN--AGDSLYVVVNAGCADKDISHINEKIKEFK

Baker's yeast                 GVVDDTIITKENDDNEFYIVTNAGCAERDTEFFHDELQNGS

Fission yeast                 GIIDDTIISKQ-DENTYYIVTNAACSEKDEANLKKHIENWK

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	29 – 403	Aminomethyltransferase, mitochondrial
Alternative sequence	113 – 156	Missing. In isoform 3.
Mutagenesis	129 – 129	D -> AN. Loss of aminomethyltransferase activity.

Literature citations

Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia.
Okamura-Ikeda K.; Hosaka H.; Yoshimura M.; Yamashita E.; Toma S.; Nakagawa A.; Fujiwara K.; Motokawa Y.; Taniguchi H.;
J. Mol. Biol. 351:1146-1159(2005)
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-403 ALONE AND IN COMPLEX WITH 5-METHYLTETRAHYDROFOLATE; SUBSTRATE-BINDING SITES; CATALYTIC ACTIVITY; FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS NKH ILE-145; ASP-269 AND HIS-320; MUTAGENESIS OF ASP-129;

Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a novel T-protein mutation (N145I): a strategy for the molecular investigation of patients with nonketotic hyperglycinemia (NKH).
Toone J.R.; Applegarth D.A.; Coulter-Mackie M.B.; James E.R.;
Mol. Genet. Metab. 72:322-325(2001)
Cited for: VARIANTS NKH ILE-145 AND HIS-320;

UniProtKB/Swiss-Prot P48728: Variant p.Asn145Ile