UniProtKB/SwissProt variant VAR

Variant information

Variant position:

944

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 Glutamate (E) to Glutamine (Q) at position 944 (E944Q, p.Glu944Gln).

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 (E) to medium size and polar (Q)

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

BLOSUM score:

2

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:

Fibrosis of extraocular muscles, congenital, 1 (CFEOM1) [MIM:135700]: A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Patients affected by congenital fibrosis of extraocular muscles type 1 show an absence of the superior division of the oculomotor nerve (cranial nerve III) and corresponding oculomotor subnuclei. {ECO:0000269|PubMed:14595441, ECO:0000269|PubMed:16157808, ECO:0000269|PubMed:17511870, ECO:0000269|PubMed:24715754}. 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 CFEOM1.

Any additional useful information about the variant.

Sequence information

Variant position:

944

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

Protein sequence length:

1674

The length of the canonical sequence.

Location on the sequence:

QLLERRVTDIIMQKMTISNM E ADMNRLLKQREELTKRREKL

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                         QLLERRVTDIIMQKMTISNMEADMNRLLKQREELTKRREKL

Mouse                         QLLERRVTDIIMQKMTISNMEADMNRLLRQREELTKRREKL

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 – 1674	Kinesin-like protein KIF21A
Coiled coil	931 – 1019
Helix	939 – 973

Literature citations

Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1.
Chan W.M.; Andrews C.; Dragan L.; Fredrick D.; Armstrong L.; Lyons C.; Geraghty M.T.; Hunter D.G.; Yazdani A.; Traboulsi E.I.; Pott J.W.; Gutowski N.J.; Ellard S.; Young E.; Hanisch F.; Koc F.; Schnall B.; Engle E.C.;
BMC Genet. 8:26-26(2007)
Cited for: VARIANTS CFEOM1 THR-356; GLN-944; GLN-954; LEU-954; TRP-954 AND PRO-1008;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q7Z4S6: Variant p.Glu944Gln