UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1073

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 Arginine (R) at position 1073 (S1073R, p.Ser1073Arg).

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 basic (R)

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

Involvement in disease:

Epilepsy, familial focal, with variable foci 1 (FFEVF1) [MIM:604364]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete. {ECO:0000269|PubMed:23542697, ECO:0000269|PubMed:23542701, ECO:0000269|PubMed:24283814, ECO:0000269|PubMed:24591017, ECO:0000269|PubMed:25366275, ECO:0000269|PubMed:26505888, ECO:0000269|PubMed:27173016}. 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 FFEVF1; inhibits slightly DEPDC5 signaling; does not change kinase activity of mTORC1; does not change association with the GATOR complex; does not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs754608531 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1073

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

Protein sequence length:

1603

The length of the canonical sequence.

Location on the sequence:

CLGEQQAAVHGGKSSAQSAE S SSVAMTPTYMDSPRKDGAFF

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                         CLGEQQAAVHGGKSSAQSAESSSVAMTPTYMDSPRKDGAFF

Mouse                         SLGEQQTTVH-GKSSTQPAENSSVAMTPTYVDSPRKDGAFF

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	1 – 1603	GATOR complex protein DEPDC5
Alternative sequence	560 – 1603	Missing. In isoform 2.
Mutagenesis	1065 – 1065	K -> R. No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1088 and R-1574.
Mutagenesis	1088 – 1088	K -> R. No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1065 and R-1574.

Literature citations

Mutations in DEPDC5 cause familial focal epilepsy with variable foci.
Dibbens L.M.; de Vries B.; Donatello S.; Heron S.E.; Hodgson B.L.; Chintawar S.; Crompton D.E.; Hughes J.N.; Bellows S.T.; Klein K.M.; Callenbach P.M.; Corbett M.A.; Gardner A.E.; Kivity S.; Iona X.; Regan B.M.; Weller C.M.; Crimmins D.; O'Brien T.J.; Guerrero-Lopez R.; Mulley J.C.; Dubeau F.; Licchetta L.; Bisulli F.; Cossette P.; Thomas P.Q.; Gecz J.; Serratosa J.; Brouwer O.F.; Andermann F.; Andermann E.; van den Maagdenberg A.M.; Pandolfo M.; Berkovic S.F.; Scheffer I.E.;
Nat. Genet. 45:546-551(2013)
Cited for: VARIANTS FFEVF1 VAL-452; ARG-1073 AND LEU-1104; INVOLVEMENT IN FFEVF1;

Preliminary functional assessment and classification of DEPDC5 variants associated with focal epilepsy.
van Kranenburg M.; Hoogeveen-Westerveld M.; Nellist M.;
Hum. Mutat. 36:200-209(2015)
Cited for: VARIANTS FFEVF1 ILE-90; LEU-272; VAL-452; GLN-485; MET-864; ARG-1073 AND GLY-1162; CHARACTERIZATON OF VARIANTS FFEVF1 ILE-90; LEU-272; VAL-452; GLN-485; MET-864; ARG-1073 AND GLY-1162; IDENTIFICATION IN GATOR COMPLEX;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75140: Variant p.Ser1073Arg