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UniProtKB/Swiss-Prot P02545: Variant p.Gly608Ser

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  608
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 Glycine (G) to Serine (S) at position 608 (G608S, p.Gly608Ser).
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 glycine (G) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 HGPS; reduced binding to SUN1; may affect splicing by activating a cryptic splice donor site.
Any additional useful information about the variant.

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



Sequence information

Variant position:  608
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  664
The length of the canonical sequence.

Location on the sequence:   CGTCGQPADKASASGSGAQV  G GPISSGSSASSVTVTRSYRS
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                         CGTCGQPADKASASGSGAQVGGPISSGSSASSVTVTRSYRS

Mouse                         CGTCGQPADKA-AGGAGAQVGGSISSGSSASSVTVTRSFRS

Rat                           CGTCGQPADKA-ASGSGAQVGGSISSGSSASSVTVTRSFRS

Pig                           CGTCGQPADKASASSSGAQVGGSISSGSSASSVTVTRSYRS

Chicken                       CGTCGQPADKGSAAAA--------SSASSASTVTVSRGYRS

Xenopus laevis                CTSCGRPAEKSVLASQGSGLVTG-SSGSSSSSVTLTRTYRS

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 – 661 Prelamin-A/C
Chain 1 – 646 Lamin-A/C
Region 384 – 664 Tail
Modified residue 612 – 612 Phosphoserine
Modified residue 613 – 613 Phosphoserine
Modified residue 616 – 616 Phosphoserine
Modified residue 619 – 619 Phosphoserine
Modified residue 628 – 628 Phosphoserine
Cross 597 – 597 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate
Cross 597 – 597 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Alternative sequence 573 – 664 Missing. In isoform C.
Alternative sequence 607 – 656 Missing. In isoform 6.


Literature citations

Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.
Eriksson M.; Brown W.T.; Gordon L.B.; Glynn M.W.; Singer J.; Scott L.; Erdos M.R.; Robbins C.M.; Moses T.Y.; Berglund P.; Dutra A.; Pak E.; Durkin S.; Csoka A.B.; Boehnke M.; Glover T.W.; Collins F.S.;
Nature 423:293-298(2003)
Cited for: ALTERNATIVE SPLICING; INVOLVEMENT IN HGPS (ISOFORM 6); VARIANTS HGPS LYS-145 AND SER-608;

Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes.
Haque F.; Mazzeo D.; Patel J.T.; Smallwood D.T.; Ellis J.A.; Shanahan C.M.; Shackleton S.;
J. Biol. Chem. 285:3487-3498(2010)
Cited for: INTERACTION WITH SUN1; CHARACTERIZATION OF VARIANTS EDMD2 PRO-527 AND PRO-530; CHARACTERIZATION OF VARIANT HGPS SER-608;

LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).
Cao H.; Hegele R.A.;
J. Hum. Genet. 48:271-274(2003)
Cited for: VARIANTS HGPS CYS-471; CYS-527 AND SER-608;

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.