UniProtKB/SwissProt variant VAR

Variant information

Variant position:

112

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 Aspartate (D) to Asparagine (N) at position 112 (D112N, p.Asp112Asn).

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 acidic (D) to medium size and polar (N)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

1

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:

Corneal dystrophy, Schnyder type (SCCD) [MIM:121800]: A form of stromal corneal dystrophy characterized by corneal clouding, resulting from abnormal deposition of cholesterol and phospholipids, and decreased visual acuity. Typically, ring-shaped yellow-white opacities composed of innumerable fine needle-shaped crystals form in Bowman layer and the adjacent anterior stroma of the central cornea. The crystals usually remain in the anterior third of the cornea. The corneal epithelium and endothelium as well as Descemet membrane are spared. {ECO:0000269|PubMed:17668063, ECO:0000269|PubMed:17962451, ECO:0000269|PubMed:18176953, ECO:0000269|PubMed:19429578, ECO:0000269|PubMed:19649163, ECO:0000269|PubMed:20489584, ECO:0000269|PubMed:20505825, ECO:0000269|PubMed:23169578, ECO:0000269|PubMed:23374346}. 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 SCCD; reduced menaquinone-4 (MK-4) synthesis.

Any additional useful information about the variant.

Sequence information

Variant position:

112

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

Protein sequence length:

338

The length of the canonical sequence.

Location on the sequence:

LAVHGAGNLVNTYYDFSKGI D HKKSDDRTLVDRILEPQDVV

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                         LAVHGAGNLVNTYYDFSKGID-HKKSDDRTLVDRILEPQDVV

Mouse                         LAVHGAGNLVNTYYDFSKGID-HKKSDDRTLVDRILEPQDV

Rat                           LAVHGAGNLVNTYYDFSKGID-HKKSDDRTLVDRILEPQDV

Chicken                       LAVHGAGNLVNTYYDFSKGID-HKKSDDRTLVDQILEPQDV

Xenopus tropicalis            LAVHGAGNLVNTYYDFSKGID-HKKSDDRTLVDHILEPQDV

Zebrafish                     LLVHGAGNLVNTYYDFSKGID-HKKSDDRTLVDQILKPQDV

Drosophila                    VTVHCAGNVVNTYFDFIKGID-KQKADDRTLVDHILTKDEV

Slime mold                    VSLQALGNVVNSFYDCKNGNDTKEKSADRTMFDFGLTEGNI

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	2 – 338	UbiA prenyltransferase domain-containing protein 1

Literature citations

UBIAD1 mutation alters a mitochondrial prenyltransferase to cause Schnyder corneal dystrophy.
Nickerson M.L.; Kostiha B.N.; Brandt W.; Fredericks W.; Xu K.P.; Yu F.S.; Gold B.; Chodosh J.; Goldberg M.; Lu da W.; Yamada M.; Tervo T.M.; Grutzmacher R.; Croasdale C.; Hoeltzenbein M.; Sutphin J.; Malkowicz S.B.; Wessjohann L.; Kruth H.S.; Dean M.; Weiss J.S.;
PLoS ONE 5:E10760-E10760(2010)
Cited for: VARIANTS SCCD THR-97; SER-102; ASN-112; GLY-122; GLU-122 AND HIS-188; SUBCELLULAR LOCATION;

The UBIAD1 prenyltransferase links menaquione-4 synthesis to cholesterol metabolic enzymes.
Nickerson M.L.; Bosley A.D.; Weiss J.S.; Kostiha B.N.; Hirota Y.; Brandt W.; Esposito D.; Kinoshita S.; Wessjohann L.; Morham S.G.; Andresson T.; Kruth H.S.; Okano T.; Dean M.;
Hum. Mutat. 34:317-329(2013)
Cited for: VARIANT GLU-177; CHARACTERIZATION OF VARIANTS SCCD SER-102; ASN-112; GLU-177 AND ARG-177; INTERACTION WITH HMGCR AND SOAT1;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y5Z9: Variant p.Asp112Asn