UniProtKB/Swiss-Prot Q8N100: Variant p.Ala47Thr

Transcription factor ATOH7
Gene: ATOH7
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Variant information Variant position:

47 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Alanine (A) to Threonine (T) at position 47 (A47T, p.Ala47Thr). 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 hydrophobic (A) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 sporadic case of optic nerve hypoplasia; uncertain significance; does not affect DNA-binding activity but reduces transcription activation. Any additional useful information about the variant.

Sequence information Variant position:

47 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

152 The length of the canonical sequence.
Location on the sequence:

GTCAGAGRLESAARRRLAAN A RERRRMQGLNTAFDRLRRVV 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                         GTCAGAGRLESAARRRLAANARERRRMQGLNTAFDRLRRVV

Mouse                         VSCAGPGRLESAARRRLAANARERRRMQGLNTAFDRLRRVV

Chicken                       VKCS-TERMESAAKRRLAANARERRRMQGLNTAFDRLRKVV

Zebrafish                     --SRDPEKFESAMRRRMAANARERKRMQGLNTAFDRLRKVV

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.

Type	Positions	Description
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
Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.
Macgregor S.; Hewitt A.W.; Hysi P.G.; Ruddle J.B.; Medland S.E.; Henders A.K.; Gordon S.D.; Andrew T.; McEvoy B.; Sanfilippo P.G.; Carbonaro F.; Tah V.; Li Y.J.; Bennett S.L.; Craig J.E.; Montgomery G.W.; Tran-Viet K.N.; Brown N.L.; Spector T.D.; Martin N.G.; Young T.L.; Hammond C.J.; Mackey D.A.;
Hum. Mol. Genet. 19:2716-2724(2010)
Cited for: VARIANTS THR-47 AND GLY-65; 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;

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.