UniProtKB/Swiss-Prot P25189: Variant p.Thr124Met

Myelin protein P0
Gene: MPZ
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Variant information Variant position:

124 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 Threonine (T) to Methionine (M) at position 124 (T124M, p.Thr124Met). 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 polar (T) to medium size and hydrophobic (M) 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 CMT1B, CMT2I and CMT2J; CMTJ2 patients present Adie pupil; slightly reduces intercellular adhesion; does not affect targeting to the cell membrane; affects glycosylation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121913595 [ dbSNP | Ensembl ]

Sequence information Variant position:

124 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

248 The length of the canonical sequence.
Location on the sequence:

DPRWKDGSIVIHNLDYSDNG T FTCDVKNPPDIVGKTSQVTL 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                         DPRWKDGSIVIHNLDYSDNGTFTCDVKNPPDIVGKTSQVTL

Mouse                         DPRWKDGSIVIHNLDYSDNGTFTCDVKNPPDIVGKTSQVTL

Rat                           DPSWKDGSIVIHNLDYSDNGTFTCDVKNPPDIVGKTSQVTL

Bovine                        DPHRKDGSIVIHNLDYGDNGTFTCDVKNPPDIVGKTSQVTL

Horse                         DPQWKDGSIVIHNLDYSDNGTFTCDVKNPPDIVGKTSQVTL

Chicken                       NPRRKDGSIVIHNLDYTDNGTFTCDVKNPPDIVGKSSQVTL

Xenopus laevis                SPKWKDASIVVHNLELTDNGTFTCDVKNPPDVVGKSSYVHL

Xenopus tropicalis            SPKWKDASIVLHNLELIDNGTFTCDVKNPPDVVGKSSYVHL

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.

Type	Positions	Description
Chain	30 – 248	Myelin protein P0
Topological domain	30 – 153	Extracellular
Domain	30 – 143	Ig-like V-type
Glycosylation	122 – 122	N-linked (GlcNAc...) (complex) asparagine
Disulfide bond	50 – 127
Beta strand	123 – 130

Literature citations
Mutations of the same sequence of the myelin P0 gene causing two different phenotypes.
Schiavon F.; Rampazzo A.; Merlini L.; Angelini C.; Mostacciuolo M.L.;
Hum. Mutat. Suppl. 1:S217-S219(1998)
Cited for: VARIANT CMT1B MET-124; VARIANT DSS 124-THR-PHE-125 DEL; The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot-Marie-Tooth phenotype.
De Jonghe P.; Timmerman V.; Ceuterick C.; Nelis E.; De Vriendt E.; Lofgren A.; Vercruyssen A.; Verellen C.; Van Maldergem L.; Martin J.-J.; Van Broeckhoven C.;
Brain 122:281-290(1999)
Cited for: VARIANT CMT2J MET-124; Axonal phenotype of Charcot-Marie-Tooth disease associated with a mutation in the myelin protein zero gene.
Chapon F.; Latour P.; Diraison P.; Schaeffer S.; Vandenberghe A.;
J. Neurol. Neurosurg. Psych. 66:779-782(1999)
Cited for: VARIANT CMT2 MET-124; Mutations in the peripheral myelin protein zero and connexin32 genes detected by non-isotopic RNase cleavage assay and their phenotypes in Japanese patients with Charcot-Marie-Tooth disease.
Yoshihara T.; Yamamoto M.; Doyu M.; Misu K.; Hattori N.; Hasegawa Y.; Mokuno K.; Mitsuma T.; Sobue G.;
Hum. Mutat. 16:177-178(2000)
Cited for: VARIANTS CMT PHE-32; CYS-68; MET-124 AND ARG-130; An axonal form of Charcot-Marie-Tooth disease showing distinctive features in association with mutations in the peripheral myelin protein zero gene (Thr124Met or Asp75Val).
Misu K.; Yoshihara T.; Shikama Y.; Awaki E.; Yamamoto M.; Hattori N.; Hirayama M.; Takegami T.; Nakashima K.; Sobue G.;
J. Neurol. Neurosurg. Psych. 69:806-811(2000)
Cited for: VARIANTS CMT2J VAL-75 AND MET-124; Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: mutation analysis in a large cohort of Italian families.
Mostacciuolo M.L.; Righetti E.; Zortea M.; Bosello V.; Schiavon F.; Vallo L.; Merlini L.; Siciliano G.; Fabrizi G.M.; Rizzuto N.; Milani M.; Baratta S.; Taroni F.;
Hum. Mutat. 18:32-41(2001)
Cited for: VARIANTS CMT1B PHE-63 AND MET-124; VARIANTS DSS CYS-98 AND 124-THR-PHE-125 DEL; Molecular analysis in Japanese patients with Charcot-Marie-Tooth disease: DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations.
Numakura C.; Lin C.; Ikegami T.; Guldberg P.; Hayasaka K.;
Hum. Mutat. 20:392-398(2002)
Cited for: VARIANTS CMT1B SER-63 DEL; ILE-65; CYS-68; CYS-82; MET-124; ARG-163 AND ARG-170; VARIANTS CMT2I VAL-75 AND ILE-113; Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients.
Hattori N.; Yamamoto M.; Yoshihara T.; Koike H.; Nakagawa M.; Yoshikawa H.; Ohnishi A.; Hayasaka K.; Onodera O.; Baba M.; Yasuda H.; Saito T.; Nakashima K.; Kira J.; Kaji R.; Oka N.; Sobue G.;
Brain 126:134-151(2003)
Cited for: VARIANTS CMT1B TYR-35; PHE-62; SER-63 DEL; CYS-68; GLU-93; CYS-98 AND PHE-146; VARIANTS CMT2I VAL-75; ARG-81; MET-124; ARG-130 AND ARG-167; Different cellular and molecular mechanisms for early and late-onset myelin protein zero mutations.
Grandis M.; Vigo T.; Passalacqua M.; Jain M.; Scazzola S.; La Padula V.; Brucal M.; Benvenuto F.; Nobbio L.; Cadoni A.; Mancardi G.L.; Kamholz J.; Shy M.E.; Schenone A.;
Hum. Mol. Genet. 17:1877-1889(2008)
Cited for: CHARACTERIZATION OF VARIANTS CMT1B 51-SER--TRP-57 DEL; PRO-39; ARG-81 AND MET-124; FUNCTION; SUBCELLULAR LOCATION; Chronic cough due to Thr124Met mutation in the peripheral myelin protein zero (MPZ gene).
Baloh R.H.; Jen J.C.; Kim G.; Baloh R.W.;
Neurology 62:1905-1906(2004)
Cited for: VARIANT CMT2 MET-124; Case records of the Massachusetts General Hospital. Case 18-2006. A 57-year-old woman with numbness and weakness of the feet and legs.
Triggs W.J.; Brown R.H. Jr.; Menkes D.L.;
N. Engl. J. Med. 354:2584-2592(2006)
Cited for: VARIANT CMT2J MET-124; INVOLVEMENT IN ADIE PUPIL;

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.