UniProtKB/SwissProt variant VAR

Variant information

Variant position:

592

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 592 (R592Q, p.Arg592Gln).

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:

Hemolytic uremic syndrome atypical 5 (AHUS5) [MIM:612925]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269|PubMed:18796626, ECO:0000269|PubMed:20513133}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.

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 AHUS5; leads to impaired binding to the regulator CD46/MCP and resistance to cleavage by factor I.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121909583 [ dbSNP | Ensembl ]

Sequence information

Variant position:

592

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

Protein sequence length:

1663

The length of the canonical sequence.

Location on the sequence:

DRQPVPGQQMTLKIEGDHGA R VVLVAVDKGVFVLNKKNKLT

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                         DRQPVPGQQMTLKIEGDHGARVVLVAVDKGVFVLNKKNKLT

Mouse                         N-HLAPGQQTTLRIEGNQGARVGLVAVDKGVFVLNKKNKLT

Rat                           NRQPAPGHQTTLRIEGNQGARVGLVAVDKGVFVLNKKNKLT

Pig                           DKQHRPGQQMTLEIQGERGARVGLVAVDKGVFVLNKKNKLT

Bovine                        EKHHRPGQQITLKIEADQGARVGLVAVDKGVFVLNKKNKLT

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	23 – 1663	Complement C3
Chain	23 – 667	Complement C3 beta chain
Chain	569 – 667	C3-beta-c
Disulfide bond	559 – 816	Interchain (between beta and alpha chains)
Beta strand	592 – 599

Literature citations

Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.
Fremeaux-Bacchi V.; Miller E.C.; Liszewski M.K.; Strain L.; Blouin J.; Brown A.L.; Moghal N.; Kaplan B.S.; Weiss R.A.; Lhotta K.; Kapur G.; Mattoo T.; Nivet H.; Wong W.; Gie S.; Hurault de Ligny B.; Fischbach M.; Gupta R.; Hauhart R.; Meunier V.; Loirat C.; Dragon-Durey M.A.; Fridman W.H.; Janssen B.J.; Goodship T.H.; Atkinson J.P.;
Blood 112:4948-4952(2008)
Cited for: VARIANTS AHUS5 GLN-592; TRP-592; TRP-735; VAL-1094; ASN-1115; TRP-1158; LYS-1161 AND ASP-1464; CHARACTERIZATION OF VARIANTS AHUS5 GLN-592; TRP-592; VAL-1094; ASN-1115 AND LYS-1161;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01024: Variant p.Arg592Gln