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UniProtKB/Swiss-Prot P63104: Variant p.Ser230Trp

14-3-3 protein zeta/delta
Gene: YWHAZ
Variant information

Variant position:  230
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Serine (S) to Tryptophan (W) at position 230 (S230W, p.Ser230Trp).
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 small size and polar (S) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Found in a patient with a neurodevelopmental disorder; unknown pathological significance; gain-of-function mutation in signal transduction; changed regulation of ERK1 and ERK2 cascade; increased interaction with BRAF; increased interaction with RAF1; loss of phosphorylation by CK1 at Thr-232.
Any additional useful information about the variant.



Sequence information

Variant position:  230
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  245
The length of the canonical sequence.

Location on the sequence:   SYKDSTLIMQLLRDNLTLWT  S DTQGDEAEAGEGGEN
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                         SYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN

Mouse                         SYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN

Rat                           SYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN

Bovine                        SYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN

Sheep                         SYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN

Chicken                       SYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN

Xenopus laevis                SYKDSTLIMQLLRDNLTLWTSDTQGDEAEQGEGGEN

Xenopus tropicalis            SYKDSTLIMQLLRDNLTLWTSDTQGDEAEQGEGGEN

Drosophila                    SYKDSTLIMQLLRDNLTLWTSDTQGDEAEPQEGGDN

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 – 245 14-3-3 protein zeta/delta
Modified residue 210 – 210 Phosphoserine
Modified residue 232 – 232 Phosphothreonine; by CK1
Mutagenesis 232 – 232 T -> A. Loss of phosphorylation by CK1.


Literature citations

A YWHAZ variant associated with cardiofaciocutaneous syndrome activates the RAF-ERK pathway.
Popov I.K.; Hiatt S.M.; Whalen S.; Keren B.; Ruivenkamp C.; van Haeringen A.; Chen M.J.; Cooper G.M.; Korf B.R.; Chang C.;
Front. Physiol. 10:388-388(2019)
Cited for: VARIANTS 14-GLU--ASN-245 DEL; ARG-53; LEU-145 AND TRP-230; CHARACTERIZATION OF VARIANT TRP-230; FUNCTION; INTERACTION WITH BRAF AND RAF1; PHOSPHORYLATION AT THR-232 BY CK1; MUTAGENESIS OF THR-232;

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.