Home  |  Contact

UniProtKB/Swiss-Prot Q8NG31: Variant p.Met2041Ile

Kinetochore scaffold 1
Gene: KNL1
Variant information

Variant position:  2041
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Methionine (M) to Isoleucine (I) at position 2041 (M2041I, p.Met2041Ile).
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:  In MCPH4; may inactivate an exonic splicing enhancer and result in abnormal splicing.
Any additional useful information about the variant.

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



Sequence information

Variant position:  2041
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2342
The length of the canonical sequence.

Location on the sequence:   GKLVQSAQNEREKLQIKIDE  M DKILKKIDNCLTEMETETKN
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                         GKLVQSAQNEREKLQIKIDEMDKILKKIDNCLTEMETETKN

Mouse                         -----------------------------SCLE--------

Caenorhabditis elegans        -----------------------------------------

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 – 2342 Kinetochore scaffold 1
Region 1834 – 2316 Necessary for kinetochore localization and for interaction with NSL1 and DSN1
Coiled coil 1942 – 2133
Alternative sequence 1773 – 2342 Missing. In isoform 3.
Alternative sequence 1860 – 2342 Missing. In isoform 4.


Literature citations

Kinetochore KMN network gene CASC5 mutated in primary microcephaly.
Genin A.; Desir J.; Lambert N.; Biervliet M.; Van Der Aa N.; Pierquin G.; Killian A.; Tosi M.; Urbina M.; Lefort A.; Libert F.; Pirson I.; Abramowicz M.;
Hum. Mol. Genet. 21:5306-5317(2012)
Cited for: VARIANT MCPH4 ILE-2041;

Refining the phenotype associated with CASC5 mutation.
Saadi A.; Verny F.; Siquier-Pernet K.; Bole-Feysot C.; Nitschke P.; Munnich A.; Abada-Dendib M.; Chaouch M.; Abramowicz M.; Colleaux L.;
Neurogenetics 17:71-78(2016)
Cited for: VARIANT MCPH4 ILE-2041;

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.