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UniProtKB/Swiss-Prot O60481: Variant p.Thr323Met

Zinc finger protein ZIC 3
Gene: ZIC3
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.



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.

TypePositionsDescription
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;

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.