UniProtKB/SwissProt variant VAR

Variant information

Variant position:

404

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 Arginine (R) to Glutamine (Q) at position 404 (R404Q, p.Arg404Gln).

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 large size and basic (R) to medium size and polar (Q)

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

Involvement in disease:

3-methylglutaconic aciduria 8 (MGCA8) [MIM:617248]: An autosomal recessive inborn error of metabolism resulting in early death. Clinical features include extreme hypertonia observed at birth, alternating with hypotonia, subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, and intractable seizures. Patients show lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, and progressive brain atrophy. {ECO:0000269|PubMed:27208207, ECO:0000269|PubMed:27696117}. 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 MGCA8; may lead to skipping of exon 7 and the resultant protein may be truncated; loss of protein expression in patient cells homozygous for the mutation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs767006508 [ dbSNP | Ensembl ]

Sequence information

Variant position:

404

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

Protein sequence length:

458

The length of the canonical sequence.

Location on the sequence:

FPDVQHGVLIHKVILGSPAH R AGLRPGDVILAIGEQMVQNA

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                         FP-DVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQMVQNA

Mouse                         FP-DVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEKLAQN

Bovine                        FP-DVQHGVLIHKVILDSPAHRAGLRPGDVILAIGEQLVQN

Drosophila                    MPSNLTHGVLVWKVIVGSPAHSGGLQPGDIVTHINKKEIKN

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	134 – 458	Serine protease HTRA2, mitochondrial
Domain	364 – 445	PDZ
Alternative sequence	314 – 458	DGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRRYIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQMVQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE -> VSETSFLPRIPAPGQCGKGRFPLIQGCLVKFLSSSLLAISQYPTRSPQHLLVLLFGCPHPLLFV. In isoform 4.
Helix	401 – 405

Literature citations

Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and 3-methylglutaconic aciduria.
Mandel H.; Saita S.; Edvardson S.; Jalas C.; Shaag A.; Goldsher D.; Vlodavsky E.; Langer T.; Elpeleg O.;
J. Med. Genet. 53:690-696(2016)
Cited for: INVOLVEMENT IN MGCA8; VARIANT MGCA8 GLN-404; CHARACTERIZATION OF VARIANT MGCA8 GLN-404;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43464: Variant p.Arg404Gln