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UniProtKB/Swiss-Prot Q9UBX5: Variant p.Gly267Ser

Fibulin-5
Gene: FBLN5
Variant information

Variant position:  267
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 267 (G267S, p.Gly267Ser).
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

Involvement in disease:  Cutis laxa, autosomal recessive, 1A (ARCL1A) [MIM:219100]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. Type I autosomal recessive cutis laxa is a specific, life-threatening disorder with organ involvement, lung atelectasis and emphysema, diverticula of the gastrointestinal and genitourinary systems, and vascular anomalies. Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon. {ECO:0000269|PubMed:12189163, ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:16691202, ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:18185537, ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:20599547}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations affecting this gene can modify the phenotype of diseases caused by ELN mutations. {ECO:0000269|PubMed:19194475}.
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.

Involvement in disease:  Macular degeneration, age-related, 3 (ARMD3) [MIM:608895]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:15269314, ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:20599547}. Note=Disease susceptibility is associated with variations 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.

Involvement in disease:  Neuropathy, hereditary, with or without age-related macular degeneration (HNARMD) [MIM:608895]: An autosomal dominant neuropathy of the Charcot-Marie-Tooth disease group, characterized by distal muscle weakness and atrophy variably affecting the lower and upper limbs. Distal sensory impairment and decreased nerve conduction velocities are present in most but not all patients. Additional variable features are age-related macular degeneration, joint hypermobility, and hyperelastic skin. {ECO:0000269|PubMed:21576112, ECO:0000269|PubMed:23328402}. 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 ARMD3, ARCL1A and HNARMD; produces protein misolding; decreases secretion; no effect on homodimerization.
Any additional useful information about the variant.

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



Sequence information

Variant position:  267
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:   DMDECSFSEFLCQHECVNQP  G TYFCSCPPGYILLDDNRSCQ
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                         DMDECSFSEFLCQHECVNQPGTYFCSCPPGYILLDDNRSCQ

Mouse                         DMDECSFSEFLCQHECVNQPGSYFCSCPPGYVLLDDNRSCQ

Rat                           DMDECSFSEFLCQHECVNQPGSYFCSCPPGYVLLEDNRSCQ

Bovine                        DMDECSFSEFLCQHECVNQPGTYFCSCPAGYILLDDNRSCQ

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 247 – 287 EGF-like 5; calcium-binding
Glycosylation 283 – 283 N-linked (GlcNAc...) asparagine
Disulfide bond 258 – 271


Literature citations

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;

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;

Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.
Auer-Grumbach M.; Weger M.; Fink-Puches R.; Papic L.; Froehlich E.; Auer-Grumbach P.; El Shabrawi-Caelen L.; Schabhuettl M.; Windpassinger C.; Senderek J.; Budka H.; Trajanoski S.; Janecke A.R.; Haas A.; Metze D.; Pieber T.R.; Guelly C.;
Brain 134:1839-1852(2011)
Cited for: VARIANTS HNARMD ILE-48; SER-90; SER-267 AND CYS-373; VARIANT MET-126;

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.