UniProtKB/SwissProt variant VAR

Variant information

Variant position:

69

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 Histidine (H) to Tyrosine (Y) at position 69 (H69Y, p.His69Tyr).

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 (H) to large size and aromatic (Y)

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

Variant description:

In EVR1; minor reduction of its wild-type activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80358282 [ dbSNP | Ensembl ]

Sequence information

Variant position:

69

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

Protein sequence length:

537

The length of the canonical sequence.

Location on the sequence:

RISMCQNLGYNVTKMPNLVG H ELQTDAELQLTTFTPLIQYG

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                         RISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYG

Mouse                         RIAMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYG

Rat                           RIAMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYG

Chicken                       RIAMCQNLGYNVTKMPNLVGHELQADAELQLTTFTPLIQYG

Xenopus laevis                RITMCQNLGYNVTKMPNLVGHELQADAELQLTTFTPLIQYG

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	37 – 537	Frizzled-4
Topological domain	37 – 212	Extracellular
Domain	40 – 161	FZ
Glycosylation	59 – 59	N-linked (GlcNAc...) asparagine
Disulfide bond	45 – 106
Disulfide bond	53 – 99

Literature citations

Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.
Kondo H.; Hayashi H.; Oshima K.; Tahira T.; Hayashi K.;
Br. J. Ophthalmol. 87:1291-1295(2003)
Cited for: VARIANTS EVR1 TYR-69; VAL-105; GLN-417 AND ASP-488;

Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R).
Omoto S.; Hayashi T.; Kitahara K.; Takeuchi T.; Ueoka Y.;
Ophthalmic Genet. 25:81-90(2004)
Cited for: VARIANTS EVR1 TYR-69 AND ARG-181;

Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.
Qin M.; Hayashi H.; Oshima K.; Tahira T.; Hayashi K.; Kondo H.;
Hum. Mutat. 26:104-112(2005)
Cited for: VARIANTS EVR1 TYR-69; VAL-105; CYS-335; VAL-342; GLN-417 AND ASP-488;

Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.
Qin M.; Kondo H.; Tahira T.; Hayashi K.;
Hum. Genet. 122:615-623(2008)
Cited for: CHARACTERIZATION OF VARIANTS EVR1 VAL-105 AND GLN-417; CHARACTERIZATION OF VARIANT TYR-69;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9ULV1: Variant p.His69Tyr