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UniProtKB/Swiss-Prot Q9H4W6: Variant p.Arg209Trp

Transcription factor COE3
Gene: EBF3
Variant information

Variant position:  209
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 Arginine (R) to Tryptophan (W) at position 209 (R209W, p.Arg209Trp).
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 large size and basic (R) 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

Involvement in disease:  Hypotonia, ataxia, and delayed development syndrome (HADDS) [MIM:617330]: An autosomal dominant neurodevelopmental syndrome characterized by global developmental delay, moderate to severe intellectual disability, cerebellar ataxia, hypotonia, speech delay, variable dysmorphic features, and genitourinary abnormalities including vesicoureteric reflux. {ECO:0000269|PubMed:28017370, ECO:0000269|PubMed:28017372, ECO:0000269|PubMed:28017373}. 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 HADDS; significant loss of transcriptional activator activity; localizes both in the cytoplasm and the nucleus; decreased chromatin-binding.
Any additional useful information about the variant.

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



Sequence information

Variant position:  209
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  596
The length of the canonical sequence.

Location on the sequence:   KFFLKCNQNCLKNAGNPRDM  R RFQVVVSTTVNVDGHVLAVS
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                         KFFLKCNQNCLKNAGNPRDMRRFQVVVSTTVNVDGHVLAVS

Mouse                         KFFLKCNQNCLKNAGNPRDMRRFQVVVSTTVNVDGHVLAVS

Xenopus laevis                KFFLKCNQNCLKNAGNPRDMRRFQVVVSTTVNVDGHVLAVS

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 – 596 Transcription factor COE3


Literature citations

Mutations in EBF3 disturb transcriptional profiles and cause intellectual disability, ataxia, and facial dysmorphism.
Harms F.L.; Girisha K.M.; Hardigan A.A.; Kortuem F.; Shukla A.; Alawi M.; Dalal A.; Brady L.; Tarnopolsky M.; Bird L.M.; Ceulemans S.; Bebin M.; Bowling K.M.; Hiatt S.M.; Lose E.J.; Primiano M.; Chung W.K.; Juusola J.; Akdemir Z.C.; Bainbridge M.; Charng W.L.; Drummond-Borg M.; Eldomery M.K.; El-Hattab A.W.; Saleh M.A.; Bezieau S.; Cogne B.; Isidor B.; Kuery S.; Lupski J.R.; Myers R.M.; Cooper G.M.; Kutsche K.;
Am. J. Hum. Genet. 100:117-127(2017)
Cited for: VARIANTS HADDS ASP-66; CYS-141; HIS-GLU-ILE-159 INS; ASP-171; LEU-177 AND TRP-209; CHARACTERIZATION OF VARIANTS HADDS ASP-66; CYS-141; HIS-GLU-ILE-159 INS; ASP-171; LEU-177 AND TRP-209; INVOLVEMENT IN HADDS; FUNCTION; SUBCELLULAR LOCATION;

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.