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UniProtKB/Swiss-Prot P32004: Variant p.Ser1194Leu

Neural cell adhesion molecule L1
Gene: L1CAM
Variant information

Variant position:  1194
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 Serine (S) to Leucine (L) at position 1194 (S1194L, p.Ser1194Leu).
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 polar (S) to medium size and hydrophobic (L)
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

Involvement in disease:  Hydrocephalus due to stenosis of the aqueduct of Sylvius (HSAS) [MIM:307000]: Hydrocephalus is a condition in which abnormal accumulation of cerebrospinal fluid in the brain causes increased intracranial pressure inside the skull. This is usually due to blockage of cerebrospinal fluid outflow in the brain ventricles or in the subarachnoid space at the base of the brain. In children is typically characterized by enlargement of the head, prominence of the forehead, brain atrophy, mental deterioration, and convulsions. In adults the syndrome includes incontinence, imbalance, and dementia. HSAS is characterized by mental retardation and enlarged brain ventricles. {ECO:0000269|PubMed:10797421, ECO:0000269|PubMed:11857550, ECO:0000269|PubMed:12435569, ECO:0000269|PubMed:12514225, ECO:0000269|PubMed:19846429, ECO:0000269|PubMed:20621658, ECO:0000269|PubMed:22344793, ECO:0000269|PubMed:22973895, ECO:0000269|PubMed:24155914, ECO:0000269|PubMed:7562969, ECO:0000269|PubMed:7762552, ECO:0000269|PubMed:7881431, ECO:0000269|PubMed:7920659, ECO:0000269|PubMed:8401576, ECO:0000269|PubMed:8556302, ECO:0000269|PubMed:8929944, ECO:0000269|PubMed:9118141, ECO:0000269|PubMed:9195224, ECO:0000269|PubMed:9268105, 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. L1CAM mutations have also been found in few patients affected by hydrocephalus with Hirschsprung disease, suggesting a role of this gene acting either in a direct or indirect way in the pathogenesis of Hirschsprung disease (PubMed:22344793). {ECO:0000269|PubMed:22344793}.
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.

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 HSAS and MASA.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  1194
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:   GEYRSLESDNEEKAFGSSQP  S LNGDIKPLGSDDSLADYGGS
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                         GEYRSLESDNEEKAFGSSQPSLNGDIKPLGSDDSLADYGGS

Mouse                         GEYRSLESDNEEKAFGSSQPSLNGDIKPLGSDDSLADYGGS

Rat                           GEYRSLESDNEEKAFGSSQPSLNGDIKPLGSDDSLADYGGS

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.

TypePositionsDescription
Chain 20 – 1257 Neural cell adhesion molecule L1
Topological domain 1144 – 1257 Cytoplasmic
Modified residue 1178 – 1178 Phosphoserine
Modified residue 1181 – 1181 Phosphoserine; by CaMK2
Modified residue 1194 – 1194 Phosphoserine


Literature citations

X-linked hydrocephalus and MASA syndrome present in one family are due to a single missense mutation in exon 28 of the L1CAM gene.
Fransen E.; Schrander-Stumpel C.; Vits L.; Coucke P.; van Camp G.; Willems P.J.;
Hum. Mol. Genet. 3:2255-2256(1994)
Cited for: VARIANT HSAS/MASA LEU-1194;

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;

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.