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UniProtKB/Swiss-Prot P32004: Variant p.Asp202Tyr

Neural cell adhesion molecule L1
Gene: L1CAM
Variant information

Variant position:  202
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 Aspartate (D) to Tyrosine (Y) at position 202 (D202Y, p.Asp202Tyr).
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 acidic (D) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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

Involvement in disease:  Mental retardation, aphasia, shuffling gait, and adducted thumbs syndrome (MASA) [MIM:303350]: An X-linked recessive syndrome with a highly variable clinical spectrum. Main clinical features include spasticity and hyperreflexia of lower limbs, shuffling gait, mental retardation, aphasia and adducted thumbs. The features of spasticity have been referred to as complicated spastic paraplegia type 1 (SPG1). Some patients manifest corpus callosum hypoplasia and hydrocephalus. Inter- and intrafamilial variability is very wide, such that patients with hydrocephalus, MASA, SPG1, and agenesis of corpus callosum can be present within the same family. {ECO:0000269|PubMed:10797421, ECO:0000269|PubMed:10805190, ECO:0000269|PubMed:11857550, ECO:0000269|PubMed:16816908, ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:22344793, ECO:0000269|PubMed:22973895, ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:26891472, ECO:0000269|PubMed:7562969, ECO:0000269|PubMed:7762552, ECO:0000269|PubMed:7881431, ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:7920660, ECO:0000269|PubMed:8556302, ECO:0000269|PubMed:9268105, ECO:0000269|PubMed:9300653, ECO:0000269|PubMed:9452110, ECO:0000269|PubMed:9521424, ECO:0000269|PubMed:9744477, ECO:0000269|PubMed:9832035}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In MASA; loss of homophilic interactions at the cell surface; no effect on localization at the cell surface.
Any additional useful information about the variant.

Sequence information

Variant position:  202
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1257
The length of the canonical sequence.

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.




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.

Chain 20 – 1257 Neural cell adhesion molecule L1
Topological domain 20 – 1120 Extracellular
Domain 139 – 226 Ig-like C2-type 2
Glycosylation 203 – 203 N-linked (GlcNAc...) asparagine
Disulfide bond 158 – 209

Literature citations

Genotype-phenotype correlations in L1 syndrome: a guide for genetic counselling and mutation analysis.
Vos Y.J.; de Walle H.E.; Bos K.K.; Stegeman J.A.; Ten Berge A.M.; Bruining M.; van Maarle M.C.; Elting M.W.; den Hollander N.S.; Hamel B.; Fortuna A.M.; Sunde L.E.; Stolte-Dijkstra I.; Schrander-Stumpel C.T.; Hofstra R.M.;
J. Med. Genet. 47:169-175(2010)
Cited for: INVOLVEMENT IN L1 SYNDROME; VARIANTS 26-TYR--GLU-1257 DEL; ASN-37; MET-38; 66-GLN--GLU-1257 DEL; 109-GLN--GLU-1257 DEL; 133-GLU--GLU-1257 DEL; 138-TRP--GLU-1257 DEL; ILE-172; GLY-184; 187-MET--VAL-198 DEL; ASP-254; ARG-276; PRO-313; 366-TRP--GLU-1257 DEL; LYS-369; 423-GLN--GLU-1257 DEL; ARG-480; ASN-516; TYR-516; HIS-525; MET-627; PRO-645; 662-TRP--GLU-1257 DEL; SER-714; ARG-754; 760-ARG--GLU-1257 DEL; 789-GLN--GLU-1257 DEL; 811-TYR--GLU-1257 DEL; 891-TYR--GLU-1257 DEL; 901-ARG--GLU-1257 DEL; 1064-SER--GLU-1257 DEL; ASN-1071 DEL AND GLN-1080; VARIANTS HSAS/MASA SER-179; ARG-335 AND MET-752; VARIANT MASA TYR-202; VARIANTS HSAS GLN-184 AND PRO-415;

Novel missense mutation in the L1 gene in a child with corpus callosum agenesis, retardation, adducted thumbs, spastic paraparesis, and hydrocephalus.
Sztriha L.; Frossard P.; Hofstra R.M.; Verlind E.; Nork M.;
J. Child Neurol. 15:239-243(2000)
Cited for: VARIANT MASA TYR-202;

L1 syndrome diagnosis complemented with functional analysis of L1CAM variants located to the two N-terminal Ig-like domains.
Christaller W.A.; Vos Y.; Gebre-Medhin S.; Hofstra R.M.; Schaefer M.K.;
Clin. Genet. 91:115-120(2017)

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.