UniProtKB/SwissProt variant VAR

Variant information

Variant position:

264

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Cysteine (C) to Tyrosine (Y) at position 264 (C264Y, p.Cys264Tyr).

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 (C) to large size and aromatic (Y)

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

Variant description:

In HSAS; severe; loss of localization to the cell surface; retention in the endoplasmic reticulum; loss of axon guidance, when assayed in a heterologous system.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137852518 [ dbSNP | Ensembl ]

Sequence information

Variant position:

264

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

1257

The length of the canonical sequence.

Location on the sequence:

FPTNSSSHLVALQGQPLVLE C IAEGFPTPTIKWLRPSGPMP

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                         FPTNSSSHLVALQGQPLVLECIAEGFPTPTIKWLRPSGPMP

Mouse                         FPTNSSSRLVALQGQSLILECIAEGFPTPTIKWLHPSDPMP

Rat                           FPTNSSSHLVALQGQSLILECIAEGFPTPTIKWLHPSDPMP

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	20 – 1257	Neural cell adhesion molecule L1
Topological domain	20 – 1120	Extracellular
Domain	240 – 328	Ig-like C2-type 3
Glycosylation	247 – 247	N-linked (GlcNAc...) asparagine
Disulfide bond	264 – 312

Literature citations

A missense mutation confirms the L1 defect in X-linked hydrocephalus (HSAS).
Jouet M.; Rosenthal A.; Macfarlane J.; Kenwrick S.; Donnai D.;
Nat. Genet. 4:331-331(1993)
Cited for: VARIANT HSAS TYR-264;

CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1.
Fransen E.; Lemmon V.; van Camp G.; Vits L.; Coucke P.; Willems P.J.;
Eur. J. Hum. Genet. 3:273-284(1995)
Cited for: VARIANT HSAS/MASA LEU-1194; VARIANTS HSAS GLN-184; TYR-264 AND ARG-452; VARIANTS MASA GLN-210 AND ASN-598;

The C264Y missense mutation in the extracellular domain of L1 impairs protein trafficking in vitro and in vivo.
Ruenker A.E.; Bartsch U.; Nave K.A.; Schachner M.;
J. Neurosci. 23:277-286(2003)
Cited for: CHARACTERIZATION OF VARIANT HSAS TYR-264; SUBCELLULAR LOCATION; GLYCOSYLATION;

Differential effects of human L1CAM mutations on complementing guidance and synaptic defects in Drosophila melanogaster.
Kudumala S.; Freund J.; Hortsch M.; Godenschwege T.A.;
PLoS ONE 8:E76974-E76974(2013)
Cited for: CHARACTERIZATION OF VARIANT VAL-120; CHARACTERIZATION OF VARIANTS MASA GLN-210 AND LYS-309; CHARACTERIZATION OF VARIANTS HSAS GLN-184; TYR-264 AND CYS-1070; MUTAGENESIS OF 1147-LYS--VAL-1153;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P32004: Variant p.Cys264Tyr