UniProtKB/SwissProt variant VAR

Variant information

Variant position:

394

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 Arginine (R) to Serine (S) at position 394 (R394S, p.Arg394Ser).

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 large size and basic (R) to small size and polar (S)

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:

Microphthalmia, syndromic, 12 (MCOPS12) [MIM:615524]: A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS12 patients manifest variable features, including diaphragmatic hernia, pulmonary hypoplasia, and cardiac abnormalities. {ECO:0000269|PubMed:24075189, ECO:0000269|PubMed:27120018}. 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 MCOPS12; increases transcriptional response to retinoic acid.

Any additional useful information about the variant.

Sequence information

Variant position:

394

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

Protein sequence length:

455

The length of the canonical sequence.

Location on the sequence:

FPKILMKITDLRSISAKGAE R VITLKMEIPGSMPPLIQEML

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                         FPKILMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEML

Mouse                         FPKILMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEML

Chicken                       FPKILMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEML

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 – 455	Retinoic acid receptor beta
Domain	183 – 417	NR LBD
Helix	373 – 401

Literature citations

Recessive and dominant mutations in retinoic acid receptor beta in cases with microphthalmia and diaphragmatic hernia.
Srour M.; Chitayat D.; Caron V.; Chassaing N.; Bitoun P.; Patry L.; Cordier M.P.; Capo-Chichi J.M.; Francannet C.; Calvas P.; Ragge N.; Dobrzeniecka S.; Hamdan F.F.; Rouleau G.A.; Tremblay A.; Michaud J.L.;
Am. J. Hum. Genet. 93:765-772(2013)
Cited for: VARIANTS MCOPS12 SER-394 AND CYS-394; CHARACTERIZATION OF VARIANTS MCOPS12 SER-394 AND CYS-394;

Gain-of-function mutations in RARB cause intellectual disability with progressive motor impairment.
Srour M.; Caron V.; Pearson T.; Nielsen S.B.; Levesque S.; Delrue M.A.; Becker T.A.; Hamdan F.F.; Kibar Z.; Sattler S.G.; Schneider M.C.; Bitoun P.; Chassaing N.; Rosenfeld J.A.; Xia F.; Desai S.; Roeder E.; Kimonis V.; Schneider A.; Littlejohn R.O.; Douzgou S.; Tremblay A.; Michaud J.L.;
Hum. Mutat. 37:786-793(2016)
Cited for: VARIANTS MCOPS12 PRO-220; ALA-303 AND CYS-394; CHARACTERIZATION OF VARIANT MCOPS12 PRO-220; ALA-303; SER-394 AND CYS-394;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10826: Variant p.Arg394Ser