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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P02545: Variant p.Gly608Ser

Prelamin-A/C
Gene: LMNA
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Variant information Variant position: help 608 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 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: help 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: help 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: help 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: help Links to websites of interest for the variant.


Sequence information Variant position: help 608 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 664 The length of the canonical sequence.
Location on the sequence: help 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         CGTCGQPADKA--SASGSGAQVGGPISSGSSASSVTVTRSYRS

Mouse                         CGTCGQPADKA---AGGAGAQVGGSISSGSSASSVTVTRSF

Rat                           CGTCGQPADKA---ASGSGAQVGGSISSGSSASSVTVTRSF

Pig                           CGTCGQPADKA--SASSSGAQVGGSISSGSSASSVTVTRSY

Chicken                       CGTCGQPADKG--SAAAA--------SSASSASTVTVSRGY

Xenopus laevis                CTSCGRPAEKSVLASQGSGLVTG---SSGSSSSSVTLTRTY

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 1 – 661 Prelamin-A/C
Chain 1 – 646 Lamin-A/C
Region 384 – 664 Tail
Region 598 – 619 Disordered
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
Glycosylation 625 – 625 O-linked (GlcNAc) serine
Glycosylation 628 – 628 O-linked (GlcNAc) serine
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.
Mutagenesis 628 – 628 S -> D. Mimics phosphorylation; causes redistribution between the nucleus and the cytoplasm during interphase; when associated with D-22 and D-392.



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.