UniProtKB/SwissProt variant VAR

Variant information

Variant position:

141

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 Asparagine (N) to Lysine (K) at position 141 (N141K, p.Asn141Lys).

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 large size and basic (K)

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 MAHCJ; does not affect ATPase activity. Loss of cobalamin transport activity. Decreases interaction with LMBD1. Does not affect lysosomal subcellular location.

Any additional useful information about the variant.

Sequence information

Variant position:

141

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

Protein sequence length:

606

The length of the canonical sequence.

Location on the sequence:

RLYFRGRAYYTLNVLRDDID N PDQRISQDVERFCRQLSSMA

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                         RLYFRGRAYYTLNVLRDDIDNPDQRISQDVERFCRQLSSMA

Mouse                         HLYFRARVYYTLNVLRDDIDNPDQRISQDVERFCRQLSSVT

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 – 606	Lysosomal cobalamin transporter ABCD4
Domain	39 – 332	ABC transmembrane type-1
Mutagenesis	141 – 141	N -> AD. Does not affect ATPase nor cobalamin transport activities.

Literature citations

Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B12-trafficking proteins ABCD4 and LMBD1.
Fettelschoss V.; Burda P.; Sagne C.; Coelho D.; De Laet C.; Lutz S.; Suormala T.; Fowler B.; Pietrancosta N.; Gasnier B.; Bornhauser B.; Froese D.S.; Baumgartner M.R.;
J. Biol. Chem. 292:11980-11991(2017)
Cited for: INVOLVEMENT IN MAHCJ; VARIANT MAHCJ GLN-432; CHARACTERIZATION OF VARIANTS MAHCJ LYS-141 AND GLN-432; SUBCELLULAR LOCATION; INTERACTION WITH LMBRD1; MUTAGENESIS OF GLY-426; LYS-427 AND ASP-548; FUNCTION; CATALYTIC ACTIVITY;

Late onset of symptoms in an atypical patient with the cblJ inborn error of vitamin B12 metabolism: diagnosis and novel mutation revealed by exome sequencing.
Kim J.C.; Lee N.C.; Hwu P.W.; Chien Y.H.; Fahiminiya S.; Majewski J.; Watkins D.; Rosenblatt D.S.;
Mol. Genet. Metab. 107:664-668(2012)
Cited for: VARIANT MAHCJ LYS-141; INVOLVEMENT IN MAHCJ;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14678: Variant p.Asn141Lys