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UniProtKB/Swiss-Prot O60481: Variant p.Pro217Ala

Zinc finger protein ZIC 3
Gene: ZIC3
Variant information

Variant position:  217
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 Proline (P) to Alanine (A) at position 217 (P217A, p.Pro217Ala).
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 hydrophobic (P) to small size and hydrophobic (A)
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 and CHTD1; lacks DNA-binding; does not inhibit transcriptional activation and interaction with GLI3; decrease in nuclear localization.
Any additional useful information about the variant.

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



Sequence information

Variant position:  217
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:   DPYRPVASPRTDPYAAGAQF  P NYSPMNMNMGVNVAAHHGPG
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                         DPYRPVASPRTDPYAAGAQFPNYSPMNMNMGVNVAAHHGPG

Mouse                         DPYRPVASPRTDPYAASAQFPNYSPMNMNMGVNVAAHHGPG

Xenopus laevis                DPYRAVPSPRTDHYAA-AQFHNYNHMNMSM--NVAAHHGQG

Xenopus tropicalis            DPYRAVPSPRTDHYAA-AQFHNYNHMNMSM--NVAAHHGPG

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


Literature citations

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;

Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects.
Ware S.M.; Peng J.; Zhu L.; Fernbach S.; Colicos S.; Casey B.; Towbin J.; Belmont J.W.;
Am. J. Hum. Genet. 74:93-105(2004)
Cited for: VARIANT CHTD1 ALA-217; VARIANTS HTX1 SER-253 AND GLU-405;

The consensus coding sequences of human breast and colorectal cancers.
Sjoeblom T.; Jones S.; Wood L.D.; Parsons D.W.; Lin J.; Barber T.D.; Mandelker D.; Leary R.J.; Ptak J.; Silliman N.; Szabo S.; Buckhaults P.; Farrell C.; Meeh P.; Markowitz S.D.; Willis J.; Dawson D.; Willson J.K.V.; Gazdar A.F.; Hartigan J.; Wu L.; Liu C.; Parmigiani G.; Park B.H.; Bachman K.E.; Papadopoulos N.; Vogelstein B.; Kinzler K.W.; Velculescu V.E.;
Science 314:268-274(2006)
Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-217;

Genetic and functional analyses of ZIC3 variants in congenital heart disease.
Cowan J.; Tariq M.; Ware S.M.;
Hum. Mutat. 35:66-75(2014)
Cited for: VARIANTS CYS-17 AND ALA-53 INS; VARIANTS CHTD1 CYS-109; ALA-217 AND GLY-447; VARIANT HTX1 ALA-217; VARIANT VACTERLX ASN-318; CHARACTERIZATION OF VARIANTS CYS-17 AND ALA-53 INS; CHARACTERIZATION OF VARIANTS CHTD1 CYS-109 AND GLY-447; CHARACTERIZATION OF VARIANT CHTD1 ALA-217; CHARACTERIZATION OF VARIANT HTX1 ALA-217; CHARACTERIZATION OF VARIANT VACTERLX ASN-318;

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.