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UniProtKB/Swiss-Prot P07196: Variant p.Pro8Leu

Neurofilament light polypeptide
Gene: NEFL
Variant information

Variant position:  8
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 Proline (P) to Leucine (L) at position 8 (P8L, p.Pro8Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Charcot-Marie-Tooth disease 1F (CMT1F) [MIM:607734]: A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1F is characterized by onset in infancy or childhood (range 1 to 13 years). {ECO:0000269|PubMed:12566280, ECO:0000269|PubMed:15241803}. 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 CMT1F.
Any additional useful information about the variant.

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

Sequence information

Variant position:  8
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  543
The length of the canonical sequence.

Location on the sequence:   MSSFSYE  P YYSTSYKRRYVETPRVHISS
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                         MSSFSYEPYYSTSYKRRYVE-TPRVHISS

Mouse                         MSSFGYDPYFSTSYKRRYVE-TPRVHIS

Rat                           MSSFSYEPYFSTSYKRRYVE-TPRVHIS

Pig                           MSSFYSEPYYSTSYKRRYVE-TPRVHIS

Bovine                        MSSFSYEPYYSTSYKRRYVE-TPRVHIS

Xenopus laevis                MSSYSYDPYY-TPYKRRVVESSPRVHI-

Xenopus tropicalis            MSSYSYDPYY-TSYKRRVVESSPRVHI-

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.

Initiator methionine 1 – 1 Removed
Chain 2 – 543 Neurofilament light polypeptide
Region 2 – 92 Head
Modified residue 2 – 2 N-acetylserine
Modified residue 23 – 23 Asymmetric dimethylarginine; alternate
Modified residue 23 – 23 Omega-N-methylarginine; alternate
Glycosylation 21 – 21 O-linked (GlcNAc) threonine
Glycosylation 27 – 27 O-linked (GlcNAc) serine

Literature citations

Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease.
Jordanova A.; De Jonghe P.; Boerkoel C.F.; Takashima H.; De Vriendt E.; Ceuterick C.; Martin J.-J.; Butler I.J.; Mancias P.; Papasozomenos S.C.; Terespolsky D.; Potocki L.; Brown C.W.; Shy M.; Rita D.A.; Tournev I.; Kremensky I.; Lupski J.R.; Timmerman V.;
Brain 126:590-597(2003)

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.