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UniProtKB/Swiss-Prot O60481: Variant p.His318Asn

Zinc finger protein ZIC 3
Gene: ZIC3
Variant information

Variant position:  318
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 Histidine (H) to Asparagine (N) at position 318 (H318N, p.His318Asn).
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:  Similar physico-chemical property. Both residues are medium size and polar.
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

Involvement in disease:  VACTERL association X-linked with or without hydrocephalus (VACTERLX) [MIM:314390]: A syndrome characterized by a non-random association of congenital defects. Affected individuals manifest vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula (TE), renal anomalies (R) such as urethral atresia with hydronephrosis, and limb anomalies (L) such as hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb. Some patients may have hydrocephalus. Some cases of VACTERL-H are associated with increased chromosome breakage and rearrangement. {ECO:0000269|PubMed:20452998, ECO:0000269|PubMed:24123890}. 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 VACTERLX; decrease in transcriptional activator activity; significant decrease in nuclear localization.
Any additional useful information about the variant.



Sequence information

Variant position:  318
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:   YWEECPREGKSFKAKYKLVN  H IRVHTGEKPFPCPFPGCGKI
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                         YWEECPREGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKI

Mouse                         YWEECPREGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKI

Xenopus laevis                YWEECPRGGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKI

Xenopus tropicalis            YWEECPRGGKSFKAKYKLVNHIRVHTGEKPFPCPFPGCGKI

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
Zinc finger 295 – 322 C2H2-type 2; atypical
Motif 297 – 322 Nuclear localization signal
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.
Helix 312 – 323


Literature citations

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.