UniProtKB/SwissProt variant VAR

Variant information

Variant position:

335

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 Valine (V) to Glycine (G) at position 335 (V335G, p.Val335Gly).

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 hydrophobic (V) to glycine (G)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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:

Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (CONDSIAS) [MIM:618170]: An autosomal recessive neurodegenerative disorder characterized by pediatric onset of progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. {ECO:0000269|PubMed:30100084, ECO:0000269|PubMed:30401461}. 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 CONDSIAS; results in accumulation of poly(ADP-ribose) in patient cells after exposure to H(2)O(2); no detectable protein levels in patient fibroblasts.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs201735454 [ dbSNP | Ensembl ]

Sequence information

Variant position:

335

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:

TDTIATMAGAIAGAYYGMDQ V PESWQQSCEGYEETDILAQS

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                         TDTIATMAGAIAGAYYGMDQVPESWQQSCEGYEETDILAQS

Mouse                         TDTIATMAGAIAGAYYGMEQVPESWQQSCEGFEETDVLAQS

Bovine                        TDTIATMAGAIAGAYYGMEQVPESWQQSCEGYEETDVLAQS

Chicken                       TNTIATMAGAIAGAYYGEEQVPPSWEQSCEAFQETQKMANS

Xenopus tropicalis            TDTIATMAAAIAGAYHGEEQIPLNWKLSAEGYKDAEDWGEK

Zebrafish                     TDTIACMAGAIAGAHYGIDSIPLSWQVSCEGVDEADDLARR

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-ribose glycohydrolase ARH3
Metal binding	316 – 316	Magnesium 1
Metal binding	316 – 316	Magnesium 2
Metal binding	317 – 317	Magnesium 2
Mutagenesis	317 – 317	T -> A. Complete loss of activity. Does not affect recruitment to DNA lesion regions following DNA damage. Retains ability to bind proteins ADP-ribosylated on serine but is unable to hydrolyze them.
Mutagenesis	317 – 317	T -> S. Partial loss of activity.

Literature citations

Bi-allelic ADPRHL2 mutations cause neurodegeneration with developmental delay, ataxia, and axonal neuropathy.
Danhauser K.; Alhaddad B.; Makowski C.; Piekutowska-Abramczuk D.; Syrbe S.; Gomez-Ospina N.; Manning M.A.; Kostera-Pruszczyk A.; Krahn-Peper C.; Berutti R.; Kovacs-Nagy R.; Gusic M.; Graf E.; Laugwitz L.; Roeblitz M.; Wroblewski A.; Hartmann H.; Das A.M.; Bueltmann E.; Fang F.; Xu M.; Schatz U.A.; Karall D.; Zellner H.; Haberlandt E.; Feichtinger R.G.; Mayr J.A.; Meitinger T.; Prokisch H.; Strom T.M.; Ploski R.; Hoffmann G.F.; Pronicki M.; Bonnen P.E.; Morlot S.; Haack T.B.;
Am. J. Hum. Genet. 103:817-825(2018)
Cited for: INVOLVEMENT IN CONDSIAS; VARIANTS CONDSIAS 248-LYS-ILE-249 DELINS ASN; GLY-335 AND 346-TYR--SER-363 DEL; FUNCTION; CHARACTERIZATION OF VARIANTS CONDSIAS 248-LYS-ILE-249 DELINS ASN AND GLY-335;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NX46: Variant p.Val335Gly