UniProtKB/Swiss-Prot O14936: Variant p.Pro396Ser

Peripheral plasma membrane protein CASK
Gene: CASK
Chromosomal location: Xp11.4
Variant information

Variant position:  396
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Proline (P) to Serine (S) at position 396 (P396S, p.Pro396Ser).
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 hydrophobic (P) to small size and polar (S)
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

Involvement in disease:  Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:300749]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Affected individuals can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus. 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 MICPCH.
Any additional useful information about the variant.



Sequence information

Variant position:  396
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  926
The length of the canonical sequence.

Location on the sequence:   QDQHLHTLLDLYDKINTKSS  P QIRNPPSDAVQRAKEVLEEI
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                         QDQHLHTLLDLYDKI-NTKSSPQIRNPPSDAVQRAKEVLEEI

Mouse                         QDQHLHTLLDLYDKI-NTKSSPQIRNPPSDAVQRAKEVLEE

Rat                           QDQHLHTLLDLYDKI-NTKSSPQIRNPPSDAVQRAKEVLEE

Drosophila                    RDNRLHQFLQLFDRIAATVVTSNGRAPAAEAVGRCRDVLEQ

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 1 – 926 Peripheral plasma membrane protein CASK
Domain 343 – 398 L27 1
Alternative sequence 386 – 386 L -> M. In isoform 5.


Literature citations

A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation.
Tarpey P.S.; Smith R.; Pleasance E.; Whibley A.; Edkins S.; Hardy C.; O'Meara S.; Latimer C.; Dicks E.; Menzies A.; Stephens P.; Blow M.; Greenman C.; Xue Y.; Tyler-Smith C.; Thompson D.; Gray K.; Andrews J.; Barthorpe S.; Buck G.; Cole J.; Dunmore R.; Jones D.; Maddison M.; Mironenko T.; Turner R.; Turrell K.; Varian J.; West S.; Widaa S.; Wray P.; Teague J.; Butler A.; Jenkinson A.; Jia M.; Richardson D.; Shepherd R.; Wooster R.; Tejada M.I.; Martinez F.; Carvill G.; Goliath R.; de Brouwer A.P.; van Bokhoven H.; Van Esch H.; Chelly J.; Raynaud M.; Ropers H.H.; Abidi F.E.; Srivastava A.K.; Cox J.; Luo Y.; Mallya U.; Moon J.; Parnau J.; Mohammed S.; Tolmie J.L.; Shoubridge C.; Corbett M.; Gardner A.; Haan E.; Rujirabanjerd S.; Shaw M.; Vandeleur L.; Fullston T.; Easton D.F.; Boyle J.; Partington M.; Hackett A.; Field M.; Skinner C.; Stevenson R.E.; Bobrow M.; Turner G.; Schwartz C.E.; Gecz J.; Raymond F.L.; Futreal P.A.; Stratton M.R.;
Nat. Genet. 41:535-543(2009)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] MICPCH HIS-268; SER-396 AND GLY-710;

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.