UniProtKB/Swiss-Prot P35398: Variant p.Thr476Ala

Nuclear receptor ROR-alpha
Gene: RORA
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Variant information Variant position:

476 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Threonine (T) to Alanine (A) at position 476 (T476A, p.Thr476Ala). 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 (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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:

No effect on cerebellar development, when assayed in a heterologous system. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs190933482 [ dbSNP | Ensembl ]

Sequence information Variant position:

476 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

523 The length of the canonical sequence.
Location on the sequence:

VLQKNHREDGILTKLICKVS T LRALCGRHTEKLMAFKAIYP 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                         VLQKNHREDGILTKLICKVSTLRALCGRHTEKLMAFKAIYP

Mouse                         VLQKNHREDGILTKLICKVSTLRALCGRHTEKLMAFKAIYP

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 – 523	Nuclear receptor ROR-alpha
Domain	272 – 510	NR LBD
Mutagenesis	484 – 484	H -> W. Almost total loss of transcriptional activity.
Helix	466 – 494

Literature citations
Dual molecular effects of dominant RORA mutations cause two variants of syndromic intellectual disability with either autism or cerebellar ataxia.
Guissart C.; Latypova X.; Rollier P.; Khan T.N.; Stamberger H.; McWalter K.; Cho M.T.; Kjaergaard S.; Weckhuysen S.; Lesca G.; Besnard T.; Ounap K.; Schema L.; Chiocchetti A.G.; McDonald M.; de Bellescize J.; Vincent M.; Van Esch H.; Sattler S.; Forghani I.; Thiffault I.; Freitag C.M.; Barbouth D.S.; Cadieux-Dion M.; Willaert R.; Guillen Sacoto M.J.; Safina N.P.; Dubourg C.; Grote L.; Carre W.; Saunders C.; Pajusalu S.; Farrow E.; Boland A.; Karlowicz D.H.; Deleuze J.F.; Wojcik M.H.; Pressman R.; Isidor B.; Vogels A.; Van Paesschen W.; Al-Gazali L.; Al Shamsi A.M.; Claustres M.; Pujol A.; Sanders S.J.; Rivier F.; Leboucq N.; Cogne B.; Sasorith S.; Sanlaville D.; Retterer K.; Odent S.; Katsanis N.; Bezieau S.; Koenig M.; Davis E.E.; Pasquier L.; Kuery S.;
Am. J. Hum. Genet. 102:744-759(2018)
Cited for: INVOLVEMENT IN IDDECA; VARIANTS IDDECA SER-90; ALA-92; ARG-94; ARG-409; GLN-462 AND 500-ARG--GLY-523 DEL; CHARACTERIZATION OF VARIANTS IDDECA ALA-92; ARG-94 AND GLN-462; FUNCTION; TISSUE SPECIFICITY; VARIANT ALA-476; CHARACTERIZATION OF VARIANT ALA-476;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.