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UniProtKB/Swiss-Prot Q9NPJ1: Variant p.Ala242Ser

McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin
Gene: MKKS
Variant information

Variant position:  242
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  US
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 Alanine (A) to Serine (S) at position 242 (A242S, p.Ala242Ser).
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 hydrophobic (A) 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

Variant description:  In MKKS and BBS6; associated with Y-84 in MKKS; unknown pathological significance; increases MKKS protein degradation; no effect on ciliogenesis; disrupts import to the nucleus; no effect on interaction with SMARCC1; may affect modulation of SMARCC1 subcellular location.
Any additional useful information about the variant.

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



Sequence information

Variant position:  242
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  570
The length of the canonical sequence.

Location on the sequence:   MSEVQLMRLLPIKKSTALKV  A LFCTTLSGDTSDTGEGTVVV
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                         MSEVQLMRLLPIKKSTALKVALFCTTLSGDTSDTGEGTVVV

Mouse                         ASEVQLRRLLPTQKASGLRVALFCTSLSGDFSNAGEGVVVA

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 – 570 McKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin
Region 198 – 370 Substrate-binding apical domain


Literature citations

Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.
Stone D.L.; Slavotinek A.M.; Bouffard G.G.; Banerjee-Basu S.; Baxevanis A.D.; Barr M.; Biesecker L.G.;
Nat. Genet. 25:79-82(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS MKKS CYS-37; TYR-84 AND SER-242; VARIANTS VAL-49 AND CYS-517;

MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.
Hirayama S.; Yamazaki Y.; Kitamura A.; Oda Y.; Morito D.; Okawa K.; Kimura H.; Cyr D.M.; Kubota H.; Nagata K.;
Mol. Biol. Cell 19:899-911(2008)
Cited for: SUBCELLULAR LOCATION; INTERACTION WITH STUB1; CHARACTERIZATION OF VARIANTS BBS6 CYS-37; ALA-57; SER-242; GLU-345 AND SER-499;

Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci.
Beales P.L.; Katsanis N.; Lewis R.A.; Ansley S.J.; Elcioglu N.; Raza J.; Woods M.O.; Green J.S.; Parfrey P.S.; Davidson W.S.; Lupski J.R.;
Am. J. Hum. Genet. 68:606-616(2001)
Cited for: VARIANTS BBS6 MET-32; ALA-57; PRO-236; ALA-286; SER-499; ALA-511 AND HIS-518; VARIANT SER-242;

Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder.
Katsanis N.; Ansley S.J.; Badano J.L.; Eichers E.R.; Lewis R.A.; Hoskins B.E.; Scambler P.J.; Davidson W.S.; Beales P.L.; Lupski J.R.;
Science 293:2256-2259(2001)
Cited for: VARIANTS BBS6 CYS-37; SER-242 AND SER-499;

Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients.
Slavotinek A.M.; Searby C.; Al-Gazali L.; Hennekam R.C.M.; Schrander-Stumpel C.; Orcana-Losa M.; Pardo-Reoyo S.; Cantani A.; Kumar D.; Capellini Q.; Neri G.; Zackai E.; Biesecker L.G.;
Hum. Genet. 110:561-567(2002)
Cited for: VARIANTS BBS6 LEU-155; SER-242 AND GLU-345; VARIANT VAL-339;

Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity.
Andersen K.L.; Echwald S.M.; Larsen L.H.; Hamid Y.H.; Glumer C.; Jorgensen T.; Borch-Johnsen K.; Andersen T.; Sorensen T.I.; Hansen T.; Pedersen O.;
J. Clin. Endocrinol. Metab. 90:225-230(2005)
Cited for: VARIANTS SER-242; CYS-517 AND VAL-532;

Bardet-Biedl syndrome in Denmark -- report of 13 novel sequence variations in six genes.
Hjortshoj T.D.; Gronskov K.; Philp A.R.; Nishimura D.Y.; Riise R.; Sheffield V.C.; Rosenberg T.; Brondum-Nielsen K.;
Hum. Mutat. 31:429-436(2010)
Cited for: VARIANT SER-242; DISCUSSION OF THE PATHOLOGICAL ROLE OF VARIANT SER-242;

Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.
Scott C.A.; Marsden A.N.; Rebagliati M.R.; Zhang Q.; Chamling X.; Searby C.C.; Baye L.M.; Sheffield V.C.; Slusarski D.C.;
PLoS Genet. 13:E1006936-E1006936(2017)
Cited for: CHARACTERIZATION OF VARIANTS MKKS CYS-37; TYR-84 AND SER-242; SUBCELLULAR LOCATION; FUNCTION; MUTAGENESIS OF LEU-454; CHARACTERIZATION OF VARIANT BBS6 CYS-37; INTERACTION WITH SMARCC1;

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.