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UniProtKB/Swiss-Prot Q13950: Variant p.Arg225Trp

Runt-related transcription factor 2
Gene: RUNX2
Variant information

Variant position:  225
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 Tryptophan (W) at position 225 (R225W, p.Arg225Trp).
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 large size and aromatic (W)
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:  Cleidocranial dysplasia (CLCD) [MIM:119600]: Autosomal dominant skeletal disorder with high penetrance and variable expressivity. It is due to defective endochondral and intramembranous bone formation. Typical features include hypoplasia/aplasia of clavicles, patent fontanelles, wormian bones (additional cranial plates caused by abnormal ossification of the calvaria), supernumerary teeth, short stature, and other skeletal changes. In some cases defects in RUNX2 are exclusively associated with dental anomalies. {ECO:0000269|PubMed:10521292, ECO:0000269|PubMed:10545612, ECO:0000269|PubMed:10689183, ECO:0000269|PubMed:10980549, ECO:0000269|PubMed:11857736, ECO:0000269|PubMed:12081718, ECO:0000269|PubMed:12196916, ECO:0000269|PubMed:12424590, ECO:0000269|PubMed:16270353, ECO:0000269|PubMed:19744171, ECO:0000269|PubMed:20082269, ECO:0000269|PubMed:20648631, ECO:0000269|PubMed:24984680, ECO:0000269|PubMed:28505335, ECO:0000269|PubMed:28703881, ECO:0000269|PubMed:28738062, ECO:0000269|PubMed:9182765, ECO:0000269|PubMed:9207800}. 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 CLCD; interferes with nuclear localization; has severely impaired DNA binding and transactivation.
Any additional useful information about the variant.

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

Sequence information

Variant position:  225
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  521
The length of the canonical sequence.

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.



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.

Chain 1 – 521 Runt-related transcription factor 2
Domain 101 – 229 Runt
Cross 238 – 238 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)

Literature citations

Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia.
Quack I.; Vonderstrass B.; Stock M.; Aylsworth A.S.; Becker A.; Brueton L.; Lee P.J.; Majewski F.; Mulliken J.B.; Suri M.; Zenker M.; Mundlos S.; Otto F.;
Am. J. Hum. Genet. 65:1268-1278(1999)
Cited for: VARIANTS CLCD ARG-113; ARG-118; CYS-121; ARG-123; ARG-205; GLN-225 AND TRP-225; VARIANT SER-511;

Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations.
Yoshida T.; Kanegane H.; Osato M.; Yanagida M.; Miyawaki T.; Ito Y.; Shigesada K.;
Am. J. Hum. Genet. 71:724-738(2002)
Cited for: VARIANTS CLCD TRP-190; SER-197; ASN-218; ILE-220; TRP-225 AND GLN-225; CHARACTERIZATION OF VARIANTS CLCD TRP-190; SER-197; ASN-218; ILE-220; TRP-225 AND GLN-225;

Mutations in the RUNX2 gene in patients with cleidocranial dysplasia.
Otto F.; Kanegane H.; Mundlos S.;
Hum. Mutat. 19:209-216(2002)
Cited for: VARIANTS CLCD GLY-156; PRO-169; TRP-190; LYS-201; TRP-225; GLN-225 AND VAL-362;

RUNX2 mutations in cleidocranial dysplasia patients.
Ryoo H.M.; Kang H.Y.; Lee S.K.; Lee K.E.; Kim J.W.;
Oral Dis. 16:55-60(2010)
Cited for: VARIANT CLCD TRP-225;

Analysis of novel RUNX2 mutations in Chinese patients with cleidocranial dysplasia.
Zhang X.; Liu Y.; Wang X.; Sun X.; Zhang C.; Zheng S.;
PLoS ONE 12:E0181653-E0181653(2017)

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.