UniProtKB/Swiss-Prot Q9NP58: Variant p.Ala492Thr

ATP-binding cassette sub-family B member 6
Gene: ABCB6
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Variant information Variant position:

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

LB/B 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 Threonine (T) at position 492 (A492T, p.Ala492Thr). 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 polar (T) 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
Polymorphism:

Genetic variations in ABCB6 define the Langereis blood group system (LAN) [MIM:111600]. Individuals with Lan(-) blood group lack the Lan antigen on their red blood cells. These individuals may have anti-Lan antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. The Lan(-) blood group is only clinically significant in transfusion settings or during pregnancy; otherwise Lan(-) individuals have no clinical features. Additional information on the polymorphism described.
Variant description:

May be a modifier of disease severity in porphyria patients; increases expression; does not affect substrate binding; impairs ATP-binding; Loss of ATP-dependent coproporphyrin III transport; Highly decrease plasma membrane expression. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs147445258 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

EVERYREAIIKYQGLEWKSS A SLVLLNQTQNLVIGLGLLAG 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                         EVERYREAIIKYQGLEWKSSASLVLLNQTQNLVIGLGLLAG

Mouse                         EVDRYREAILKFQGLEWKSTASLVVLNQTQNLVIGLGLLAG

Rat                           ELERYREAILKFQGLEWKSTASLVLLNQTQNMVIGFGLLAG

Xenopus tropicalis            EVGRFNDSIMKYQVSEWKVNASLAMLNQTQNLIIGLGLLAG

Slime mold                    ERKRYDFALMDFFQTNKKSKVSYFLLNFGQSSIIVIGTTLG

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 – 842	ATP-binding cassette sub-family B member 6
Topological domain	419 – 499	Cytoplasmic
Domain	265 – 556	ABC transmembrane type-1
Mutagenesis	498 – 498	N -> Q. Does not affect N-glycosylation. Does not affect N-glycosylation; when associated with Q-447; Q-677 and Q-775. Does not affect trafficking from endoplasmic reticulum; when associated with Q-447; Q-677 and Q-775.
Helix	469 – 521

Literature citations
The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6.
Fukuda Y.; Cheong P.L.; Lynch J.; Brighton C.; Frase S.; Kargas V.; Rampersaud E.; Wang Y.; Sankaran V.G.; Yu B.; Ney P.A.; Weiss M.J.; Vogel P.; Bond P.J.; Ford R.C.; Trent R.J.; Schuetz J.D.;
Nat. Commun. 7:12353-12353(2016)
Cited for: VARIANTS GLN-192; TRP-276; THR-492; SER-521; SER-588 AND THR-681; CHARACTERIZATION OF VARIANTS TRP-276; THR-492 AND SER-521; CATALYTIC ACTIVITY; FUNCTION; SUBCELLULAR LOCATION;

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.