UniProtKB/Swiss-Prot Q01668: Variant p.Val401Leu

Voltage-dependent L-type calcium channel subunit alpha-1D
Gene: CACNA1D
Feedback?

Variant information Variant position:

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

US 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 Valine (V) to Leucine (L) at position 401 (V401L, p.Val401Leu). 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:

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
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.

Sequence information Variant position:

401 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:

LPWVYFVSLVIFGSFFVLNL V LGVLSGEFSKEREKAKARGD 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                         LPWVYFVSLVIFGSFFVLNLVLGVLSGEFSKEREKAKARGD

Mouse                         WPWVYFVSLIILGSFFVLNLVLGVLSGEFSKEREKAKARGD

Rat                           WPWVYFVSLIILGSFFVLNLVLGVLSGEFSKEREKAKARGD

Chicken                       WPWIYFVSLIILGSFFVLNLVLGVLSGEFSKEREKAKARGD

Drosophila                    WQWMYFISMVILGAFFVMNLILGVLSGEFSKERNKAKNRGD

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	382 – 406	Helical; Name=S6 of repeat I
Repeat	113 – 409	I
Helix	395 – 415

Literature citations
New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy.
Pinggera A.; Mackenroth L.; Rump A.; Schallner J.; Beleggia F.; Wollnik B.; Striessnig J.;
Hum. Mol. Genet. 26:2923-2932(2017)
Cited for: INVOLVEMENT IN AUTISM SPECTRUM DISORSERS; FUNCTION; VARIANT LEU-401; CHARACTERIZATION OF VARIANT LEU-401;

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.