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UniProtKB/Swiss-Prot Q9UBX5: Variant p.Ser227Pro

Fibulin-5
Gene: FBLN5
Variant information

Variant position:  227
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 Serine (S) to Proline (P) at position 227 (S227P, p.Ser227Pro).
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 small size and polar (S) to medium size and hydrophobic (P)
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 ARCL1A; decreases expression; produces protein misfolding; abolishes secretion; reduces interaction with ELN; increases homodimerization; impairs elastic fiber development.
Any additional useful information about the variant.

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



Sequence information

Variant position:  227
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  448
The length of the canonical sequence.

Location on the sequence:   DVNECATENPCVQTCVNTYG  S FICRCDPGYELEEDGVHCSD
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                         DVNECATENPCVQTCVNTYGSFICRCDPGYELEEDGVHCSD

Mouse                         DVNECETENPCVQTCVNTYGSFICRCDPGYELEEDGIHCSD

Rat                           DVNECETENPCVQTCVNTYGSFICRCDPGYELEEDGIHCSD

Bovine                        DVNECATENPCVQTCVNTYGSFICRCDPGYELEDDGVHCSD

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 24 – 448 Fibulin-5
Domain 207 – 246 EGF-like 4; calcium-binding
Disulfide bond 217 – 230


Literature citations

Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa.
Loeys B.; van Maldergem L.; Mortier G.; Coucke P.; Gerniers S.; Naeyaert J.-M.; de Paepe A.;
Hum. Mol. Genet. 11:2113-2118(2002)
Cited for: VARIANT ARCL1A PRO-227;

Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa.
Hu Q.; Loeys B.L.; Coucke P.J.; De Paepe A.; Mecham R.P.; Choi J.; Davis E.C.; Urban Z.;
Hum. Mol. Genet. 15:3379-3386(2006)
Cited for: VARIANTS ARCL1A ARG-217 AND PRO-227; CHARACTERIZATION OF VARIANTS ARCL1A ARG-217 AND PRO-227; FUNCTION; INTERACTION WITH ELN; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa.
Lotery A.J.; Baas D.; Ridley C.; Jones R.P.; Klaver C.C.; Stone E.; Nakamura T.; Luff A.; Griffiths H.; Wang T.; Bergen A.A.; Trump D.;
Hum. Mutat. 27:568-574(2006)
Cited for: VARIANTS ARMD3 LEU-60; GLN-71; SER-87; PRO-124; THR-169; SER-267; TRP-351; THR-363 AND GLU-412; CHARACTERIZATION OF VARIANTS ARMD3 LEU-60; GLN-71; SER-87; PRO-124; THR-169; SER-267; TRP-351; THR-363 AND GLU-412; VARIANTS ARCL1A ARG-217 AND PRO-227; CHARACTERIZATION OF VARIANTS ARCL1A ARG-217 AND PRO-227; VARIANTS MET-126 AND ARG-202; SUBCELLULAR LOCATION;

Homozygous missense mutation in fibulin-5 in an Iranian autosomal recessive cutis laxa pedigree and associated haplotype.
Elahi E.; Kalhor R.; Banihosseini S.S.; Torabi N.; Pour-Jafari H.; Houshmand M.; Amini S.S.H.; Ramezani A.; Loeys B.;
J. Invest. Dermatol. 126:1506-1509(2006)
Cited for: VARIANT ARCL1A PRO-227;

Structural effects of fibulin 5 missense mutations associated with age-related macular degeneration and cutis laxa.
Jones R.P.; Ridley C.; Jowitt T.A.; Wang M.C.; Howard M.; Bobola N.; Wang T.; Bishop P.N.; Kielty C.M.; Baldock C.; Lotery A.J.; Trump D.;
Invest. Ophthalmol. Vis. Sci. 51:2356-2362(2010)
Cited for: CHARACTERIZATION OF VARIANTS MET-126 AND ARG-202; CHARACTERIZATION OF VARIANTS ARMD3 LEU-60; GLN-71; SER-87; PRO-124; THR-169; SER-267; TRP-351 AND GLU-412; CHARACTERIZATION OF VARIANTS ARCL1A ARG-217 AND PRO-227; SUBUNIT;

Biophysical characterisation of fibulin-5 proteins associated with disease.
Schneider R.; Jensen S.A.; Whiteman P.; McCullagh J.S.; Redfield C.; Handford P.A.;
J. Mol. Biol. 401:605-617(2010)
Cited for: CHARACTERIZATION OF VARIANTS ARCL1A PRO-227 AND SER-267; CHARACTERIZATION OF VARIANT ARMD3 THR-169; CHARACTERIZATION OF VARIANT ARG-202; SUBCELLULAR LOCATION;

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.