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UniProtKB/Swiss-Prot Q96L73: Variant p.Arg2005Gln

Histone-lysine N-methyltransferase, H3 lysine-36 specific
Gene: NSD1
Variant information

Variant position:  2005
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 2005 (R2005Q, p.Arg2005Gln).
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:  Sotos syndrome 1 (SOTOS1) [MIM:117550]: A childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, mental retardation, advanced bone age, and abnormal craniofacial morphology including macrodolichocephaly with frontal bossing, frontoparietal sparseness of hair, apparent hypertelorism, downslanting palpebral fissures, and facial flushing. Common oral findings include: premature eruption of teeth; high, arched palate; pointed chin and, more rarely, prognathism. {ECO:0000269|PubMed:11896389, ECO:0000269|PubMed:12464997, ECO:0000269|PubMed:12807965, ECO:0000269|PubMed:14997421}. 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 SOTOS1; strongly reduced enzyme activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  2005
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2696
The length of the canonical sequence.

Location on the sequence:   IRYAQEHDITNFYMLTLDKD  R IIDAGPKGNYARFMNHCCQP
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                         IRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHCCQP

Mouse                         IRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHCCQP

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.

TypePositionsDescription
Chain 1 – 2696 Histone-lysine N-methyltransferase, H3 lysine-36 specific
Domain 1942 – 2059 SET
Beta strand 2005 – 2013


Literature citations

The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation.
Qiao Q.; Li Y.; Chen Z.; Wang M.; Reinberg D.; Xu R.M.;
J. Biol. Chem. 286:8361-8368(2011)
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1852-2082 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND ZINC IONS; FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF ARG-1914 AND ARG-1952; CHARACTERIZATION OF SOTOS1 VARIANTS GLN-1984; GLN-2005 AND GLN-2017;

NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.
Douglas J.; Hanks S.; Temple I.K.; Davies S.; Murray A.; Upadhyaya M.; Tomkins S.; Hughes H.E.; Cole T.R.P.; Rahman N.;
Am. J. Hum. Genet. 72:132-143(2003)
Cited for: VARIANTS SOTOS1 LEU-1616; PRO-1637; TRP-1674; VAL-1792; ARG-1925; GLN-2005; GLN-2017; GLN-2143 AND SER-2183; VARIANTS LEU-614; THR-691; PRO-726; PRO-1036; ILE-1091; ILE-2250 AND THR-2261;

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.