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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q5HYA8: Variant p.Met252Thr

Meckelin
Gene: TMEM67
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Variant information Variant position: help 252 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Methionine (M) to Threonine (T) at position 252 (M252T, p.Met252Thr). 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: help Change from medium size and hydrophobic (M) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In MKS3, JBTS6 and COACH1; loss of interaction with WNT5A. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 252 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 995 The length of the canonical sequence.
Location on the sequence: help SSAAACWVYANLTSCQALGN M CVMNMNSYDFATFDACGLFQ 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         SSAAACWVYANLTSCQALGNMCVMNMNSYDFATFDACGLFQ

Mouse                         ATAAACWTHANLTSCQALGNMCVMNMNSYDSTTLDACRLFH

Rat                           ATAAACWTHSNLTSCQALGNMCVMNMNSYDSTTFDACRLFH

Sequence annotation in neighborhood: help 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 37 – 995 Meckelin
Topological domain 37 – 519 Extracellular
Region 37 – 280 Cysteine-rich
Glycosylation 242 – 242 N-linked (GlcNAc...) asparagine
Helix 243 – 255



Literature citations
Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3.
Consugar M.B.; Kubly V.J.; Lager D.J.; Hommerding C.J.; Wong W.C.; Bakker E.; Gattone V.H. II; Torres V.E.; Breuning M.H.; Harris P.C.;
Hum. Genet. 121:591-599(2007)
Cited for: VARIANTS MKS3 208-ARG--ILE-995 DEL; THR-252; GLN-440; 451-ARG--ILE-995 DEL AND PRO-966; Mutation spectrum of Meckel syndrome genes: one group of syndromes or several distinct groups?
Tallila J.; Salonen R.; Kohlschmidt N.; Peltonen L.; Kestilae M.;
Hum. Mutat. 30:E813-E830(2009)
Cited for: VARIANTS MKS3 CYS-54; PHE-245; THR-252; CYS-296; GLN-440; CYS-513; ARG-615 AND PRO-966; Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11).
Otto E.A.; Tory K.; Attanasio M.; Zhou W.; Chaki M.; Paruchuri Y.; Wise E.L.; Wolf M.T.F.; Utsch B.; Becker C.; Nuernberg G.; Nuernberg P.; Nayir A.; Saunier S.; Antignac C.; Hildebrandt F.;
J. Med. Genet. 46:663-670(2009)
Cited for: VARIANTS NPHP11 LEU-290; ARG-615; SER-821 AND ARG-821; VARIANTS JBTS6 44-GLN--ILE-995 DEL; 208-ARG--ILE-995 DEL; THR-252; ARG-615; ARG-821 AND THR-833; Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis).
Doherty D.; Parisi M.A.; Finn L.S.; Gunay-Aygun M.; Al-Mateen M.; Bates D.; Clericuzio C.; Demir H.; Dorschner M.; van Essen A.J.; Gahl W.A.; Gentile M.; Gorden N.T.; Hikida A.; Knutzen D.; Ozyurek H.; Phelps I.; Rosenthal P.; Verloes A.; Weigand H.; Chance P.F.; Dobyns W.B.; Glass I.A.;
J. Med. Genet. 47:8-21(2010)
Cited for: VARIANTS COACH1 ASN-99; ARG-130; GLN-172; SER-242; THR-252; VAL-257; SER-349; LEU-358; LYS-372; GLU-376; CYS-441; SER-485; CYS-513; ARG-615; LEU-637; THR-833; PRO-841 AND CYS-942; VARIANTS JBTS6 ARG-82 AND SER-82; The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway.
Abdelhamed Z.A.; Natarajan S.; Wheway G.; Inglehearn C.F.; Toomes C.; Johnson C.A.; Jagger D.J.;
Dis. Model. Mech. 8:527-541(2015)
Cited for: CHARACTERIZATION OF VARIANTS MKS3 THR-252; SER-349; PRO-376; GLN-440; CYS-549 AND ARG-615; INTERACTION WITH WNT5A AND ROR2; FUNCTION;
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.