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UniProtKB/Swiss-Prot P35555: Variant p.Ile2741Thr

Fibrillin-1
Gene: FBN1
Variant information

Variant position:  2741
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 Isoleucine (I) to Threonine (T) at position 2741 (I2741T, p.Ile2741Thr).
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 hydrophobic (I) to medium size and polar (T)
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

Involvement in disease:  Marfan lipodystrophy syndrome (MFLS) [MIM:616914]: A syndrome characterized by congenital lipodystrophy, a progeroid facial appearance due to lack of subcutaneous fat, and variable signs of Marfan syndrome. Clinical features include premature birth with an accelerated linear growth disproportionate to the weight gain, ectopia lentis, aortic dilatation, dural ectasia, and arachnodactyly. Mental and motor development are within normal limits. {ECO:0000269|PubMed:20979188, ECO:0000269|PubMed:21594992, ECO:0000269|PubMed:21594993, ECO:0000269|PubMed:24039054, ECO:0000269|PubMed:24613577, ECO:0000269|PubMed:24665001, ECO:0000269|PubMed:26860060, ECO:0000269|PubMed:27087445}. Note=The disease is caused by mutations affecting the gene represented in this entry. Asprosin: Mutations specifically affect Asprosin, a hormone peptide present at the C-terminus of Fibrillin-1 chain, which is cleaved from Fibrillin-1 following secretion (PubMed:27087445). {ECO:0000269|PubMed:27087445}.
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 MFLS.
Any additional useful information about the variant.



Sequence information

Variant position:  2741
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2871
The length of the canonical sequence.

Location on the sequence:   NGYPKRGRKRRSTNETDASN  I EDQSETEANVSLASWDVEKT
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                         NGYPKRGRKRRSTNETDASNIEDQSETEANVSLASWDVEKT

Mouse                         NGYPKRGRKRRSTNETDASDIQDGSEMEANVSLASWDVEKP

Pig                           NGYPKRGRKRRSTNETDAFNIEDQPETESNVSLASWDVEKT

Bovine                        NGYPKRGRKRRSANETDASNIEDQPEIEANVSLASWDVEKT

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 2732 – 2871 Asprosin
Glycosylation 2734 – 2734 N-linked (GlcNAc...) asparagine
Glycosylation 2750 – 2750 N-linked (GlcNAc...) asparagine
Mutagenesis 2728 – 2728 R -> A. Abolishes furin cleavage site, leading to defects in protein processing at the C-terminus.
Mutagenesis 2731 – 2731 R -> K. Abolishes furin cleavage site, leading to defects in protein processing at the C-terminus.
Mutagenesis 2732 – 2732 S -> T. Defects in protein processing at the C-terminus.


Literature citations

De novo heterozygous FBN1 mutations in the extreme C-terminal region cause progeroid fibrillinopathy.
Garg A.; Xing C.;
Am. J. Med. Genet. A 164A:1341-1345(2014)
Cited for: INVOLVEMENT IN MFLS (ASPROSIN); VARIANT MFLS THR-2741;

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.