UniProtKB/SwissProt variant VAR

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

167 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 Histidine (H) to Tyrosine (Y) at position 167 (H167Y, p.His167Tyr). 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 medium size and polar (H) to large size and aromatic (Y) 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
Variant description:

In AGS5; loss of function in defense response to virus; loss of oligomerization; decreased ability to restrict LINE-1 retrotransposon activity. Any additional useful information about the variant.

Sequence information Variant position:

167 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:

IKQLGGGYYVFPGASHNRFE H SLGVGYLAGCLVHALGEKQP 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                         IKQLGGGYYVFPGASHNRFEHSLGVGYLAGCLVHALGEKQP

Mouse                         IKQLGGGYYVFPGASHNRFEHSLGVGYLAGCLVRALAEKQP

Bovine                        IKQLGGGYYVFPGASHNRFEHSLGVGYLAGRLVRELSEKQP

Chicken                       IKQLGGTYFVFPGASHNRFEHSLGVGYLAGCLVRELKERQP

Xenopus laevis                IKQLGGSYYVFPGASHNRFEHSIGVGYLAGCLVQALHERQP

Zebrafish                     IKQLGGTYLVFPGASHNRFEHSIGVGYLAGCLVKALNERQP

Caenorhabditis elegans        LKQTGLVYLVYPNCEHSRFVHSLGTFSLAYALVDKLRHSQP

Slime mold                    LKQVGTTSFVFPCASHSRFEHSIGVSHLAGKYIDRIKVTQP

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
Binding site	149 – 149
Binding site	149 – 149
Binding site	149 – 149
Binding site	149 – 149
Binding site	150 – 150
Binding site	156 – 156	in chain C
Binding site	156 – 156	in chain C
Binding site	156 – 156	in chain C
Binding site	156 – 156	in chain C
Binding site	164 – 164
Binding site	164 – 164
Binding site	164 – 164
Binding site	164 – 164
Binding site	167 – 167
Mutagenesis	149 – 149	Q -> A. Abolished dNTPase activity without affecting homotetramerization. Abolished dNTPase activity; when associated with A-319.
Mutagenesis	164 – 164	R -> A. Abolished ability to restrict infection by viruses.
Mutagenesis	167 – 167	H -> A. Abolished ability to restrict infection by viruses.
Helix	164 – 185

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; Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutieres syndrome.
Ramantani G.; Kohlhase J.; Hertzberg C.; Innes A.M.; Engel K.; Hunger S.; Borozdin W.; Mah J.K.; Ungerath K.; Walkenhorst H.; Richardt H.H.; Buckard J.; Bevot A.; Siegel C.; von Stuelpnagel C.; Ikonomidou C.; Thomas K.; Proud V.; Niemann F.; Wieczorek D.; Haeusler M.; Niggemann P.; Baltaci V.; Conrad K.; Lebon P.; Lee-Kirsch M.A.;
Arthritis Rheum. 62:1469-1477(2010)
Cited for: VARIANTS AGS5 TYR-167 AND HIS-290;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y3Z3: Variant p.His167Tyr