UniProtKB/SwissProt variant VAR

Variant information

Variant position:

417

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 Asparagine (N) to Serine (S) at position 417 (N417S, p.Asn417Ser).

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 (N) to small size and polar (S)

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:

Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal translocation t(5;11)(q31;q23) with KMT2A/MLL1 has been found in leukemic cells from JMML patients, also carrying inactivating mutations on the second allele (PubMed:10908648). {ECO:0000269|PubMed:10908648}.

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 JMML; somatic mutation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121918546 [ dbSNP | Ensembl ]

Sequence information

Variant position:

417

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

Protein sequence length:

814

The length of the canonical sequence.

Location on the sequence:

IHAVETRGINEQGLYRIVGV N SRVQKLLSVLMDPKTASETE

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                         IHAVETRGINEQGLYRIVGVNSRVQKLLSVLMDPKTASETE

Mouse                         IHAVETRGINEQGLYRIVGVNSRVQKLLSVLMDPKAASETE

Chicken                       IHAVETRGINEQGLYRIVGVNSRVQKLLSILMDPKTATETE

Xenopus laevis                IQAIETRGINEQGLYRIVGVNSRVQKLLNILMDPKISPETE

Xenopus tropicalis            IQAVETRGINEQGLYRIVGVNSRVQKLLNFLMDPKISPETE

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 – 814	Rho GTPase-activating protein 26
Domain	383 – 568	Rho-GAP

Literature citations

The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q.
Borkhardt A.; Bojesen S.; Haas O.A.; Fuchs U.; Bartelheimer D.; Loncarevic I.F.; Bohle R.M.; Harbott J.; Repp R.; Jaeger U.; Viehmann S.; Henn T.; Korth P.; Scharr D.; Lampert F.;
Proc. Natl. Acad. Sci. U.S.A. 97:9168-9173(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2); DISEASE; VARIANT JMML SER-417;

UniProtKB/Swiss-Prot Q9UNA1: Variant p.Asn417Ser