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UniProtKB/Swiss-Prot Q9NPJ1: Variant p.Tyr37Cys

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

Variant position:  37
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 Tyrosine (Y) to Cysteine (C) at position 37 (Y37C, p.Tyr37Cys).
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 large size and aromatic (Y) to medium size and polar (C)
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:  Bardet-Biedl syndrome 6 (BBS6) [MIM:605231]: A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:10973238, ECO:0000269|PubMed:10973251, ECO:0000269|PubMed:11179009, ECO:0000269|PubMed:11567139, ECO:0000269|PubMed:12107442, ECO:0000269|PubMed:12677556, ECO:0000269|PubMed:12920096, ECO:0000269|PubMed:15666242, ECO:0000269|PubMed:15731008, ECO:0000269|PubMed:15770229, ECO:0000269|PubMed:18094050, ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:21344540, ECO:0000269|PubMed:22152675, ECO:0000269|PubMed:26900326, ECO:0000269|PubMed:28753627, ECO:0000269|PubMed:28761321}. 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.

Involvement in disease:  McKusick-Kaufman syndrome (MKKS) [MIM:236700]: Autosomal recessive developmental disorder. It is characterized by hydrometrocolpos, postaxial polydactyly and congenital heart defects. {ECO:0000269|PubMed:10802661, ECO:0000269|PubMed:28753627}. 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 MKKS and BBS6; causes both increased MKKS protein degradation and reduced solubility relative to wild-type and Tyr-84 mutant; the mutant is immobilized at the centrosome even in the absence of proteasome inhibition; the mutant is also highly polyubiquitinated; no effect on import to the nucleus.
Any additional useful information about the variant.

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



Sequence information

Variant position:  37
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:   LTTERVRTTLSVLKRIVTSC  Y GPSGRLKQLHNGFGGYVCTT
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                         LTTERVRTTLSVLKRIVTSCYGPSGRLKQLHNGFGGYVCTT

Mouse                         LTSEKVRSTLSVLKGVIASCYGPSGRLKQLHNGLGGCVYTT

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


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;

BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly.
Seo S.; Baye L.M.; Schulz N.P.; Beck J.S.; Zhang Q.; Slusarski D.C.; Sheffield V.C.;
Proc. Natl. Acad. Sci. U.S.A. 107:1488-1493(2010)
Cited for: FUNCTION; IDENTIFICATION IN A MULTIPROTEIN COMPLEX; INTERACTION WITH BBS2; CHARACTERIZATION OF VARIANTS BBS6 CYS-37; ASP-52; ALA-57; TYR-84; PRO-236 AND PRO-277;

Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.
Katsanis N.; Beales P.L.; Woods M.O.; Lewis R.A.; Green J.S.; Parfrey P.S.; Ansley S.J.; Davidson W.S.; Lupski J.R.;
Nat. Genet. 26:67-70(2000)
Cited for: VARIANTS BBS6 CYS-37; ALA-57 AND PRO-277;

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;

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.