UniProtKB/SwissProt variant VAR

Variant information

Variant position:

37

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 37 (G37S, p.Gly37Ser).

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:

Aicardi-Goutieres syndrome 4 (AGS4) [MIM:610333]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:17846997, ECO:0000269|PubMed:20131292}. 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 AGS4; strongly impairs enzyme activity but not interaction with RNASEH2B and RNASEH2C.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs76857106 [ dbSNP | Ensembl ]

Sequence information

Variant position:

37

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

Protein sequence length:

299

The length of the canonical sequence.

Location on the sequence:

SSPVPAVCRKEPCVLGVDEA G RGPVLGPMVYAICYCPLPRL

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                         SSPVPAVCRKE---PCVLGVDEAGRGPVLGPMVYAICYCPLPRL

Mouse                         SSPVPAVCLKE---PCVLGVDEAGRGPVLGPMVYAICYCPL

Rat                           SSPVPAVCLKE---PCVLGVDEAGRGPVLGPMVYAICYCPL

Bovine                        SSPVPPVCLKE---PCVLGVDEAGRGPVLGPMVYAICYCPL

Caenorhabditis elegans        NNFGNGI-------PCVLGIDEAGRGPVLGPMVYAAAISPL

Drosophila                    SD-VPDICKDK---PCMLGVDEAGRGPVLGPMVYGISYCPL

Slime mold                    TELDSSVDKSE---PFVMGIDEAGRGPVMGPMVYGCCYAPI

Baker's yeast                 FSPVPSALLEQNDSPIIMGIDEAGRGPVLGPMVYAVAYSTQ

Fission yeast                 STVTDDISKSQ---PYRLGVDEAGRGPVLGPMVYAVAYCPV

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 – 299	Ribonuclease H2 subunit A
Metal binding	34 – 34	Divalent metal cation
Metal binding	35 – 35	Divalent metal cation

Literature citations

Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection.
Crow Y.J.; Leitch A.; Hayward B.E.; Garner A.; Parmar R.; Griffith E.; Ali M.; Semple C.; Aicardi J.; Babul-Hirji R.; Baumann C.; Baxter P.; Bertini E.; Chandler K.E.; Chitayat D.; Cau D.; Dery C.; Fazzi E.; Goizet C.; King M.D.; Klepper J.; Lacombe D.; Lanzi G.; Lyall H.; Martinez-Frias M.L.; Mathieu M.; McKeown C.; Monier A.; Oade Y.; Quarrell O.W.; Rittey C.D.; Rogers R.C.; Sanchis A.; Stephenson J.B.P.; Tacke U.; Till M.; Tolmie J.L.; Tomlin P.; Voit T.; Weschke B.; Woods C.G.; Lebon P.; Bonthron D.T.; Ponting C.P.; Jackson A.P.;
Nat. Genet. 38:910-916(2006)
Cited for: VARIANT AGS4 SER-37; CHARACTERIZATION OF VARIANT AGS4 SER-37; FUNCTION; INTERACTION WITH RNASEH2B AND RNASEH2C;

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.
Rice G.; Patrick T.; Parmar R.; Taylor C.F.; Aeby A.; Aicardi J.; Artuch R.; Montalto S.A.; Bacino C.A.; Barroso B.; Baxter P.; Benko W.S.; Bergmann C.; Bertini E.; Biancheri R.; Blair E.M.; Blau N.; Bonthron D.T.; Briggs T.; Brueton L.A.; Brunner H.G.; Burke C.J.; Carr I.M.; Carvalho D.R.; Chandler K.E.; Christen H.J.; Corry P.C.; Cowan F.M.; Cox H.; D'Arrigo S.; Dean J.; De Laet C.; De Praeter C.; Dery C.; Ferrie C.D.; Flintoff K.; Frints S.G.; Garcia-Cazorla A.; Gener B.; Goizet C.; Goutieres F.; Green A.J.; Guet A.; Hamel B.C.; Hayward B.E.; Heiberg A.; Hennekam R.C.; Husson M.; Jackson A.P.; Jayatunga R.; Jiang Y.H.; Kant S.G.; Kao A.; King M.D.; Kingston H.M.; Klepper J.; van der Knaap M.S.; Kornberg A.J.; Kotzot D.; Kratzer W.; Lacombe D.; Lagae L.; Landrieu P.G.; Lanzi G.; Leitch A.; Lim M.J.; Livingston J.H.; Lourenco C.M.; Lyall E.G.; Lynch S.A.; Lyons M.J.; Marom D.; McClure J.P.; McWilliam R.; Melancon S.B.; Mewasingh L.D.; Moutard M.L.; Nischal K.K.; Ostergaard J.R.; Prendiville J.; Rasmussen M.; Rogers R.C.; Roland D.; Rosser E.M.; Rostasy K.; Roubertie A.; Sanchis A.; Schiffmann R.; Scholl-Burgi S.; Seal S.; Shalev S.A.; Corcoles C.S.; Sinha G.P.; Soler D.; Spiegel R.; Stephenson J.B.; Tacke U.; Tan T.Y.; Till M.; Tolmie J.L.; Tomlin P.; Vagnarelli F.; Valente E.M.; Van Coster R.N.; Van der Aa N.; Vanderver A.; Vles J.S.; Voit T.; Wassmer E.; Weschke B.; Whiteford M.L.; Willemsen M.A.; Zankl A.; Zuberi S.M.; Orcesi S.; Fazzi E.; Lebon P.; Crow Y.J.;
Am. J. Hum. Genet. 81:713-725(2007)
Cited for: VARIANTS AGS4 SER-37; TRP-108; TRP-186; LEU-230; GLN-235; MET-240 AND HIS-291; VARIANTS ASP-99; SER-202; GLU-205 AND GLY-260;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75792: Variant p.Gly37Ser