UniProtKB/SwissProt variant VAR

ADP-ribosylhydrolase ARH3
Gene: ADPRS
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Variant information Variant position:

79 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 Threonine (T) to Proline (P) at position 79 (T79P, p.Thr79Pro). 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 (T) to medium size and hydrophobic (P) 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 CONDSIAS; severely reduced protein levels in patient fibroblasts; decreased stability and reduced Tm; reduced alpha-helix content and altered secondary structure detected by circular dichroism spectroscopy. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1557733311 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

EPDPGTPGSERTEALYYTDD T AMARALVQSLLAKEAFDEVD 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                         EPDPGT---PGSERTEALYYTDDTAMARALVQSLLAKEAFDEVD

Mouse                         EPDPGT---PGSARTETLYYTDDTAMTRALVQSLLAKEAFD

Bovine                        EPDPGS---PGSARTEALCYTDDTAMARALVQSLLAKEAFD

Chicken                       EPPGGEGEPAGSARRETLSYTDDTAMSRCVVQSLLAKREFD

Xenopus tropicalis            D--------KGERLKRVLTYTDDTAMARSIVQSVLENYEFN

Zebrafish                     EDDTRG---DG-----ILQYSDDTAMMRCVADSLLTRMTFD

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 – 363	ADP-ribosylhydrolase ARH3
Binding site	76 – 76
Binding site	77 – 77
Binding site	77 – 77
Binding site	78 – 78
Binding site	78 – 78
Modified residue	64 – 64	Phosphothreonine
Mutagenesis	76 – 76	T -> R. Abolishes hydrolase activity.
Mutagenesis	77 – 77	D -> NA. Complete loss of activity. Abolishes Mg(2+) binding. Retains ability to bind ADP-ribose. Does not affect recruitment to DNA lesion regions following DNA damage. Strongly reduced ability to hydrolyze proteins ADP-ribosylated on serine.
Mutagenesis	78 – 78	D -> A. Abolishes hydrolase activity.
Mutagenesis	78 – 78	D -> N. Complete loss of activity.
Helix	77 – 92

Literature citations
Biallelic mutations in ADPRHL2, encoding ADP-ribosylhydrolase 3, lead to a degenerative pediatric stress-induced epileptic ataxia syndrome.
Ghosh S.G.; Becker K.; Huang H.; Dixon-Salazar T.; Chai G.; Salpietro V.; Al-Gazali L.; Waisfisz Q.; Wang H.; Vaux K.K.; Stanley V.; Manole A.; Akpulat U.; Weiss M.M.; Efthymiou S.; Hanna M.G.; Minetti C.; Striano P.; Pisciotta L.; De Grandis E.; Altmueller J.; Nuernberg P.; Thiele H.; Yis U.; Okur T.D.; Polat A.I.; Amiri N.; Doosti M.; Karimani E.G.; Toosi M.B.; Haddad G.; Karakaya M.; Wirth B.; van Hagen J.M.; Wolf N.I.; Maroofian R.; Houlden H.; Cirak S.; Gleeson J.G.;
Am. J. Hum. Genet. 103:431-439(2018)
Cited for: INVOLVEMENT IN CONDSIAS; VARIANTS CONDSIAS ASN-34; PRO-79; 106-GLN--SER-363 DEL; LEU-177 AND 334-GLN--SER-363 DEL; CHARACTERIZATION OF VARIANTS CONDSIAS PRO-79; 106-GLN--SER-363 DEL AND 334-GLN--SER-363 DEL;

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 Q9NX46: Variant p.Thr79Pro