UniProtKB/SwissProt variant VAR

Variant information

Variant position:

225

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

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Glutamine (Q) at position 225 (R225Q, p.Arg225Gln).

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

Variant description:

In CLCD1; interferes with nuclear localization; abolishes DNA binding.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104893991 [ dbSNP | Ensembl ]

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.

Location on the sequence:

TNPPQVATYHRAIKVTVDGP R EPRRHRQKLDDSKPSLFSDR

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                         TNPPQVATYHRAIKVTVDGPREPRRHRQKLDDSKPSLFSDR

Mouse                         TNPPQVATYHRAIKVTVDGPREPRRHRQKLDDSKPSLFSDR

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 – 521	Runt-related transcription factor 2
Domain	101 – 229	Runt
Region	222 – 340	Disordered
Compositional bias	222 – 242	Basic and acidic residues
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 CLCD1 ARG-113; ARG-118; CYS-121; ARG-123; ARG-205; GLN-225 AND TRP-225; VARIANT SER-511;

CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia.
Zhou G.; Chen Y.; Zhou L.; Thirunavukkarasu K.; Hecht J.; Chitayat D.; Gelb B.D.; Pirinen S.; Berry S.A.; Greenberg C.R.; Karsenty G.; Lee B.;
Hum. Mol. Genet. 8:2311-2316(1999)
Cited for: VARIANTS CLCD1 ASN-133 DEL; GLN-169; ARG-175; GLN-190; ASN-191; CYS-193; PHE-199; ALA-200; ARG-209 AND GLN-225;

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 CLCD1 TRP-190; SER-197; ASN-218; ILE-220; TRP-225 AND GLN-225; CHARACTERIZATION OF VARIANTS CLCD1 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 CLCD1 GLY-156; PRO-169; TRP-190; LYS-201; TRP-225; GLN-225 AND VAL-362;

Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype.
Kim H.-J.; Nam S.-H.; Kim H.-J.; Park H.-S.; Ryoo H.-M.; Kim S.-Y.; Cho T.-J.; Kim S.-G.; Bae S.-C.; Kim I.-S.; Stein J.L.; van Wijnen A.J.; Stein G.S.; Lian J.B.; Choi J.-Y.;
J. Cell. Physiol. 207:114-122(2006)
Cited for: VARIANTS CLCD1 GLY-131 AND GLN-225;

A novel RUNX2 mutation in exon 8, G462X, in a patient with Cleidocranial Dysplasia.
Jung Y.J.; Bae H.S.; Ryoo H.M.; Baek S.H.;
J. Cell. Biochem. 119:1152-1162(2018)
Cited for: VARIANTS CLCD1 ARG-175; GLN-190; GLN-225 AND 462-GLY--TYR-521 DEL; CHARACTERIZATION OF VARIANT CLCD1 462-GLY--TYR-521 DEL; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13950: Variant p.Arg225Gln