UniProtKB/Swiss-Prot Q96PY6: Variant p.Leu253Ser

Serine/threonine-protein kinase Nek1
Gene: NEK1
Chromosomal location: 4q33
Variant information

Variant position:  253
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 Leucine (L) to Serine (S) at position 253 (L253S, p.Leu253Ser).
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 (L) to small size and polar (S)
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:  Short-rib thoracic dysplasia 6 with or without polydactyly (SRTD6) [MIM:263520]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:22499340}. Note=The disease is caused by mutations affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617). {ECO:0000269|PubMed:21211617}.
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 SRTD6.
Any additional useful information about the variant.



Sequence information

Variant position:  253
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1258
The length of the canonical sequence.

Location on the sequence:   SLVSQLFKRNPRDRPSVNSI  L EKGFIAKRIEKFLSPQLIAE
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.

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 – 1258 Serine/threonine-protein kinase Nek1
Domain 4 – 258 Protein kinase
Helix 249 – 253


Literature citations

NEK1 and DYNC2H1 are both involved in short rib polydactyly Majewski type but not in Beemer Langer cases.
El Hokayem J.; Huber C.; Couve A.; Aziza J.; Baujat G.; Bouvier R.; Cavalcanti D.P.; Collins F.A.; Cordier M.P.; Delezoide A.L.; Gonzales M.; Johnson D.; Le Merrer M.; Levy-Mozziconacci A.; Loget P.; Martin-Coignard D.; Martinovic J.; Mortier G.R.; Perez M.J.; Roume J.; Scarano G.; Munnich A.; Cormier-Daire V.;
J. Med. Genet. 49:227-233(2012)
Cited for: VARIANTS SRTD6 ARG-145 AND SER-253;

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.