UniProtKB/SwissProt variant VAR

Variant information

Variant position:

578

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 Histidine (H) to Glutamine (Q) at position 578 (H578Q, p.His578Gln).

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 polar.

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

Involvement in disease:

Ichthyosis, congenital, autosomal recessive 2 (ARCI2) [MIM:242100]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:11773004, ECO:0000269|PubMed:15629692, ECO:0000269|PubMed:16116617, ECO:0000269|PubMed:19131948, ECO:0000269|PubMed:19890349}. 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 ARCI2; complete loss of the enzyme activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137853024 [ dbSNP | Ensembl ]

Sequence information

Variant position:

578

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

Protein sequence length:

701

The length of the canonical sequence.

Location on the sequence:

RTVPELIRYVTIVIYTCSAK H AAVNTGQMEFTAWMPNFPAS

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                         RTVPELIRYVTIVIYTCSAKHAAVNTGQMEFTAWMPNFPAS

Mouse                         RTIPELIEYVTMVMYTCSARHAAVNSGQLEYTSWMPNFPSS

Rat                           RTVPELIEYVTMVMYTCSARHAAVNTGQLEYTSWMPNFPSS

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 – 701	Arachidonate 12-lipoxygenase, 12R-type
Domain	120 – 701	Lipoxygenase
Metal binding	578 – 578	Iron; catalytic
Metal binding	582 – 582	Iron; catalytic

Literature citations

Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1.
Jobard F.; Lefevre C.; Karaduman A.; Blanchet-Bardon C.; Emre S.; Weissenbach J.; Ozguc M.; Lathrop M.; Prud'homme J.-F.; Fischer J.;
Hum. Mol. Genet. 11:107-113(2002)
Cited for: VARIANTS ARCI2 PRO-426 AND GLN-578;

Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3.
Yu Z.; Schneider C.; Boeglin W.E.; Brash A.R.;
Biochim. Biophys. Acta 1686:238-247(2005)
Cited for: CHARACTERIZATION OF VARIANTS ARCI2 PRO-426 AND GLN-578;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75342: Variant p.His578Gln