UniProtKB/Swiss-Prot O00555: Variant p.Arg1672Pro

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 1672 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 Arginine (R) to Proline (P) at position 1672 (R1672P, p.Arg1672Pro). 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 medium size and hydrophobic (P) 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
Polymorphism: The poly-Gln region of CACNA1A is polymorphic: 6 to 17 repeats in the normal population, expanded to about 21 to 30 repeats in SCA6. Repeat expansion has been reported also in a EA2 family. Additional information on the polymorphism described.
Variant description: Found in a patient with global developmental delay and cerebellar ataxia; likely pathogenic; gain of function observed in the Drosophila homolog. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs1057519429 [ dbSNP | Ensembl ]

Sequence information

Variant position: 1672 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 2506 The length of the canonical sequence.
Location on the sequence: NFINLSFLRLFRAARLIKLL R QGYTIRILLWTFVQSFKALP 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.
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 – 2506	Voltage-dependent P/Q-type calcium channel subunit alpha-1A
Topological domain	1671 – 1689	Cytoplasmic
Repeat	1550 – 1813	IV
Helix	1665 – 1673

Literature citations

Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially.
Luo X.; Rosenfeld J.A.; Yamamoto S.; Harel T.; Zuo Z.; Hall M.; Wierenga K.J.; Pastore M.T.; Bartholomew D.; Delgado M.R.; Rotenberg J.; Lewis R.A.; Emrick L.; Bacino C.A.; Eldomery M.K.; Coban Akdemir Z.; Xia F.; Yang Y.; Lalani S.R.; Lotze T.; Lupski J.R.; Lee B.; Bellen H.J.; Wangler M.F.;
PLoS Genet. 13:E1006905-E1006905(2017)
Cited for: VARIANTS GLN-1663 AND PRO-1672; CHARACTERIZATION OF VARIANTS GLN-1663 AND PRO-1672;