UniProtKB/Swiss-Prot Q9Y3Z3: Variant p.Met254Val

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
Gene: SAMHD1
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Variant information Variant position:

254 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 Methionine (M) to Valine (V) at position 254 (M254V, p.Met254Val). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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 AGS5; loss of function in defense response to virus; does not affect oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121434521 [ dbSNP | Ensembl ]

Sequence information Variant position:

254 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

626 The length of the canonical sequence.
Location on the sequence:

EQGSVMMFEHLINSNGIKPV M EQYGLIPEEDICFIKEQIVG 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                         EQGSVMMFEHLINSNGIKP----VMEQYGLIPEEDICFIKEQIVG

Mouse                         EQGSIEMFEHLVNSNELKL----VMKNYGLVPEEDITFIKE

Bovine                        EQGSVMMFEHLINSNGLQD----VMKYYGLIPEEDILFIKE

Chicken                       ETASVEMFEHLITSNKLEE----IMESYGLILEEDIAFIKE

Xenopus laevis                ESASVAMFDHLIQSNGLEE----AMKENGLCLPDDLTFIKE

Zebrafish                     EIASVQMFDHLVEVNGLEA----VMLHHGMRLPEDLIFIKE

Caenorhabditis elegans        EDMSILIIKKIMNKPEIKSEFACILGETDEEYAKSVTLITE

Slime mold                    EDMSIKMLNWIIDDHGLDE-----------YDSDDIKFISS

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 – 626	Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
Domain	164 – 316	HD
Helix	250 – 256

Literature citations
Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutieres syndrome-related SAMHD1.
Zhao K.; Du J.; Han X.; Goodier J.L.; Li P.; Zhou X.; Wei W.; Evans S.L.; Li L.; Zhang W.; Cheung L.E.; Wang G.; Kazazian H.H. Jr.; Yu X.F.;
Cell Rep. 4:1108-1115(2013)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS AGS5 PRO-123; HIS-143; GLN-145; TYR-167; ASN-201; SER-209; VAL-254 AND HIS-290; A SAMHD1 mutation associated with Aicardi-Goutieres Syndrome uncouples the ability of SAMHD1 to restrict HIV-1 from its ability to downmodulate type I interferon in humans.
White T.E.; Brandariz-Nunez A.; Martinez-Lopez A.; Knowlton C.; Lenzi G.; Kim B.; Ivanov D.; Diaz-Griffero F.;
Hum. Mutat. 38:658-668(2017)
Cited for: FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS AGS5 PRO-123; CYS-143; HIS-143; GLN-145; TYR-167; ASN-201; SER-209; VAL-254; HIS-290; SER-369; VAL-385 AND THR-448; MUTAGENESIS OF ARG-226; ASP-311 AND GLN-548; Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.
Rice G.I.; Bond J.; Asipu A.; Brunette R.L.; Manfield I.W.; Carr I.M.; Fuller J.C.; Jackson R.M.; Lamb T.; Briggs T.A.; Ali M.; Gornall H.; Couthard L.R.; Aeby A.; Attard-Montalto S.P.; Bertini E.; Bodemer C.; Brockmann K.; Brueton L.A.; Corry P.C.; Desguerre I.; Fazzi E.; Cazorla A.G.; Gener B.; Hamel B.C.J.; Heiberg A.; Hunter M.; van der Knaap M.S.; Kumar R.; Lagae L.; Landrieu P.G.; Lourenco C.M.; Marom D.; McDermott M.F.; van der Merwe W.; Orcesi S.; Prendiville J.S.; Rasmussen M.; Shalev S.A.; Soler D.M.; Shinawi M.; Spiegel R.; Tan T.Y.; Vanderver A.; Wakeling E.L.; Wassmer E.; Whittaker E.; Lebon P.; Stetson D.B.; Bonthron D.T.; Crow Y.J.;
Nat. Genet. 41:829-832(2009)
Cited for: VARIANTS AGS5 PRO-123; CYS-143; HIS-143; GLN-145; ASN-201; SER-209; VAL-254; SER-369 AND VAL-385; FUNCTION; SUBCELLULAR LOCATION; Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.
Rice G.I.; Forte G.M.; Szynkiewicz M.; Chase D.S.; Aeby A.; Abdel-Hamid M.S.; Ackroyd S.; Allcock R.; Bailey K.M.; Balottin U.; Barnerias C.; Bernard G.; Bodemer C.; Botella M.P.; Cereda C.; Chandler K.E.; Dabydeen L.; Dale R.C.; De Laet C.; De Goede C.G.; Del Toro M.; Effat L.; Enamorado N.N.; Fazzi E.; Gener B.; Haldre M.; Lin J.P.; Livingston J.H.; Lourenco C.M.; Marques W. Jr.; Oades P.; Peterson P.; Rasmussen M.; Roubertie A.; Schmidt J.L.; Shalev S.A.; Simon R.; Spiegel R.; Swoboda K.J.; Temtamy S.A.; Vassallo G.; Vilain C.N.; Vogt J.; Wermenbol V.; Whitehouse W.P.; Soler D.; Olivieri I.; Orcesi S.; Aglan M.S.; Zaki M.S.; Abdel-Salam G.M.; Vanderver A.; Kisand K.; Rozenberg F.; Lebon P.; Crow Y.J.;
Lancet Neurol. 12:1159-1169(2013)
Cited for: VARIANTS AGS5 120-ASP--HIS-123 DEL; PRO-123; HIS-143; ASN-201; VAL-254; VAL-385 AND THR-448;

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.