UniProtKB/SwissProt variant VAR

Variant information

Variant position:

149

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 Serine (S) to Phenylalanine (F) at position 149 (S149F, p.Ser149Phe).

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 large size and aromatic (F)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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:

Periventricular nodular heterotopia 1 (PVNH1) [MIM:300049]: A developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH1 is an X-linked dominant form. Heterozygous females have normal intelligence but suffer from seizures and various manifestations outside the central nervous system, especially related to the vascular system. Hemizygous affected males die in the prenatal or perinatal period. {ECO:0000269|PubMed:11532987, ECO:0000269|PubMed:11914408, ECO:0000269|PubMed:15249610, ECO:0000269|PubMed:15668422, ECO:0000269|PubMed:15994863, ECO:0000269|PubMed:16299064}. 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 PVNH1.

Any additional useful information about the variant.

Sequence information

Variant position:

149

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

Protein sequence length:

2647

The length of the canonical sequence.

Location on the sequence:

IVDGNLKLILGLIWTLILHY S ISMPMWDEEEDEEAKKQTPK

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                         IVDGNLKLILGLIWTLILHYSISMPMWDEEEDEE--AKKQTPK

Mouse                         IVDGNLKLILGLIWTLILHYSISMPMWDEEEDEE--AKKQT

Drosophila                    IVDCKLKLILGLIWTLILHYSISMPMWDGEDDKQLNGSGHT

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.

Type	Positions	Description
Chain	2 – 2647	Filamin-A
Domain	43 – 149	Calponin-homology (CH) 1
Region	2 – 274	Actin-binding
Cross	135 – 135	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	135 – 135	K -> R. Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-43.
Helix	134 – 149

Literature citations

Germline and mosaic mutations of FLN1 in men with periventricular heterotopia.
Guerrini R.; Mei D.; Sisodiya S.M.; Sicca F.; Harding B.; Takahashi Y.; Dorn T.; Yoshida A.; Campistol J.; Kraemer G.; Moro F.; Dobyns W.B.; Parrini E.;
Neurology 63:51-56(2004)
Cited for: VARIANTS PVNH1 VAL-102 AND PHE-149;

UniProtKB/Swiss-Prot P21333: Variant p.Ser149Phe