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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8N100: Variant p.Asn46His

Transcription factor ATOH7
Gene: ATOH7
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Variant information Variant position: help 46 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Asparagine (N) to Histidine (H) at position 46 (N46H, p.Asn46His). 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: help 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: help 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: help In PHPVAR; loss of function; polypeptide is stable, but does not bind DNA or activate transcription; does not restore retinal ganglion cell development in retinal explants from a mouse Atoh7 null mutant; abolishes heterodimerization with TCF3 E47 isoform; reduces DNA-binding ability and abolishes transcriptional activation; no effect on nuclear localization. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 46 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 152 The length of the canonical sequence.
Location on the sequence: help AGTCAGAGRLESAARRRLAA N ARERRRMQGLNTAFDRLRRV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         AGTCAGAGRLESAARRRLAANARERRRMQGLNTAFDRLRRV

Mouse                         AVSCAGPGRLESAARRRLAANARERRRMQGLNTAFDRLRRV

Chicken                       VVKCS-TERMESAAKRRLAANARERRRMQGLNTAFDRLRKV

Zebrafish                     ---SRDPEKFESAMRRRMAANARERKRMQGLNTAFDRLRKV
Sequence annotation in neighborhood: help 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 – 152 Transcription factor ATOH7
Domain 40 – 92 bHLH
Mutagenesis 56 – 56 L -> P. Loss of DNA-binding activity; loss of ability to restore retinal ganglion cell development in retinal explants from a mouse Atoh7 null mutant.
Mutagenesis 59 – 59 A -> G. Abolishes heterodimerization with TCF3 isoform E47; no effect on nuclear localization.



Literature citations
ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous.
Prasov L.; Masud T.; Khaliq S.; Mehdi S.Q.; Abid A.; Oliver E.R.; Silva E.D.; Lewanda A.; Brodsky M.C.; Borchert M.; Kelberman D.; Sowden J.C.; Dattani M.T.; Glaser T.;
Hum. Mol. Genet. 21:3681-3694(2012)
Cited for: VARIANT PHPVAR HIS-46; CHARACTERIZATION OF VARIANT PHPVAR HIS-46; VARIANTS THR-47 AND GLY-65; CHARACTERIZATION OF VARIANTS THR-47 AND GLY-65; MUTAGENESIS OF LEU-56; Atonal homolog 7 (ATOH7) loss-of-function mutations in predominant bilateral optic nerve hypoplasia.
Atac D.; Koller S.; Hanson J.V.M.; Feil S.; Tiwari A.; Bahr A.; Baehr L.; Magyar I.; Kottke R.; Gerth-Kahlert C.; Berger W.;
Hum. Mol. Genet. 29:132-148(2020)
Cited for: VARIANTS VAL-59 AND THR-59; CHARACTERIZATION OF VARIANTS HIS-46; VAL-59 AND THR-59; FUNCTION; INTERACTION WITH TCF3; SUBCELLULAR LOCATION; MUTAGENESIS OF ALA-59;
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.