UniProtKB/SwissProt variant VAR

Variant information

Variant position:

323

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 Threonine (T) to Methionine (M) at position 323 (T323M, p.Thr323Met).

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 (T) to medium size and hydrophobic (M)

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 HTX1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs122462165 [ dbSNP | Ensembl ]

Sequence information

Variant position:

323

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

Protein sequence length:

467

The length of the canonical sequence.

Location on the sequence:

PREGKSFKAKYKLVNHIRVH T GEKPFPCPFPGCGKIFARSE

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                         PREGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKIFARSE

Mouse                         PREGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKIFARSE

Xenopus laevis                PRGGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKIFARSE

Xenopus tropicalis            PRGGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKIFARSE

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 – 467	Zinc finger protein ZIC 3
Mutagenesis	304 – 304	R -> M. Increases its cytoplasmic localization.
Mutagenesis	307 – 307	K -> M. Increases its cytoplasmic localization.
Mutagenesis	310 – 310	K -> M. Increases its cytoplasmic localization.
Mutagenesis	312 – 312	K -> M. Increases its cytoplasmic localization.
Mutagenesis	314 – 314	K -> M. Does not increase its cytoplasmic localization.
Mutagenesis	320 – 320	R -> A. Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-337; A-341; A-346; A-349 and A-350.
Mutagenesis	326 – 326	K -> M. Does not increase its cytoplasmic localization.
Mutagenesis	337 – 337	K -> A. Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-320; A-341; A-346; A-349 and A-350.
Mutagenesis	341 – 341	R -> A. Increases its cytoplasmic localization. Does not interact with KPNA1 and KPNA6 and increases strongly its cytoplasmic localization; when associated with A-320; A-337; A-346; A-349 and A-350.
Helix	312 – 323

Literature citations

X-linked situs abnormalities result from mutations in ZIC3.
Gebbia M.; Ferrero G.B.; Pilia G.; Bassi M.T.; Aylsworth A.S.; Penman-Splitt M.; Bird L.M.; Bamforth J.S.; Burn J.; Schlessiner D.; Nelson D.L.; Casey B.;
Nat. Genet. 17:305-308(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS HTX1 ARG-286 AND MET-323;

Characterization of the interactions of human ZIC3 mutants with GLI3.
Zhu L.; Zhou G.; Poole S.; Belmont J.W.;
Hum. Mutat. 29:99-105(2008)
Cited for: FUNCTION; INTERACTION WITH GLI3; DNA-BINDING; CHARACTERIZATION OF VARIANTS HTX1 SER-253; ARG-286; MET-323 AND GLU-405; CHARACTERIZATION OF VARIANT CHTD1 ALA-217;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60481: Variant p.Thr323Met