UniProtKB/SwissProt variant VAR

Variant information

Variant position:

220

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 Leucine (L) to Proline (P) at position 220 (L220P, p.Leu220Pro).

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 hydrophobic.

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

BLOSUM score:

-3

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 MCOPS12; increased transcriptional response to retinoic acid ligands.

Any additional useful information about the variant.

Sequence information

Variant position:

220

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:

PSLCQLGKYTTNSSADHRVR L DLGLWDKFSELATKCIIKIV

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                         PSLCQLGKYTTNSSADHRVRLDLGLWDKFSELATKCIIKIV

Mouse                         PSLCQLGKYTTNSSADHRVRLDLGLWDKFSELATKCIIKIV

Chicken                       PSLCQLGKYTTNSSADHRVRLDLGLWDKFSELATKCIIKIV

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
Mutagenesis	222 – 222	L -> I. Reduced transcriptional activation in the absence of hormone. Even greater reduction in transcriptional activation in the absence of hormone; when associated with D-223 or S-232. Great reduction in transcriptional activation in the absence of hormone; when associated with D-223 and S-232.
Mutagenesis	223 – 223	G -> D. Greatly reduced transcriptional activation in the absence of hormone. Even greater reduction in transcriptional activation in the absence of hormone; when associated with I-222 or S-232. Great reduction in transcriptional activation in the absence of hormone; when associated with I-222 and S-232.
Mutagenesis	232 – 232	A -> S. Reduced transcriptional activation in the absence of hormone. Some further reduction of transcriptional activity in the absence of hormone; when associated with I-222 or D-223. Great reduction in transcriptional activation in the absence of hormone; when associated with I-222 and D-223.

Literature citations

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.Leu220Pro