UniProtKB/Swiss-Prot Q01668: Variant p.Ala749Gly

Voltage-dependent L-type calcium channel subunit alpha-1D
Gene: CACNA1D
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Variant information Variant position:

749 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 Alanine (A) to Glycine (G) at position 749 (A749G, p.Ala749Gly). 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 small size and hydrophobic (A) to glycine (G) 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
Polymorphism:

A change from seven to eight ATG trinucleotide repeats, resulting in an additional N-terminal methionine, has been found in a patient with non-insulin-dependent diabetes mellitus (NIDDM). Additional information on the polymorphism described.
Variant description:

Found in a patient with autism spectrum disorder; likely pathogenic; gain of function; increases channel activity; the mutant channel is activated at less depolarized potentials with an increased current density and impaired channel inactivation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2094979008 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

2161 The length of the canonical sequence.
Location on the sequence:

CIYFIILFICGNYILLNVFL A IAVDNLADAESLNTAQKEEA 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                         CIYFIILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEA

Mouse                         CIYFIILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEA

Rat                           CIYFIILFICGNYILLKLFLAIAVDNLADAESLNTAQKEEA

Chicken                       CIYFIILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEA

Drosophila                    CIYFIILFICGNYILLNVFLAIAVDNLADADSLSEVEKEEE

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 – 2161	Voltage-dependent L-type calcium channel subunit alpha-1D
Transmembrane	728 – 752	Helical; Name=S6 of repeat II
Repeat	509 – 755	II
Helix	748 – 753

Literature citations
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
O'Roak B.J.; Vives L.; Girirajan S.; Karakoc E.; Krumm N.; Coe B.P.; Levy R.; Ko A.; Lee C.; Smith J.D.; Turner E.H.; Stanaway I.B.; Vernot B.; Malig M.; Baker C.; Reilly B.; Akey J.M.; Borenstein E.; Rieder M.J.; Nickerson D.A.; Bernier R.; Shendure J.; Eichler E.E.;
Nature 485:246-250(2012)
Cited for: VARIANT GLY-749; CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels.
Pinggera A.; Lieb A.; Benedetti B.; Lampert M.; Monteleone S.; Liedl K.R.; Tuluc P.; Striessnig J.;
Biol. Psychiatry 77:816-822(2015)
Cited for: INVOLVEMENT IN AUTISM SPECTRUM DISORSERS; FUNCTION; CHARACTERIZATION OF VARIANTS ARG-407 AND GLY-749;

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.