UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1061

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

Type of variant:

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:

From Leucine (L) to Proline (P) at position 1061 (L1061P, p.Leu1061Pro).

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 hydrophobic.

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:

In HSCR1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs536486113 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1061

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

Protein sequence length:

1114

The length of the canonical sequence.

Location on the sequence:

VDCNNAPLPRALPSTWIENK L YGMSDPNWPGESPVPLTRAD

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                         VDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRAD

Mouse                         VDCNNAPLPRSLPSTWIENKLYGMSDPNWPGESPVPLTRAD

Rat                           VDCNSAPLPRSLPSTWIENKLYGMSDPNWPGESPVPLTRAD

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	29 – 1114	Proto-oncogene tyrosine-protein kinase receptor Ret
Topological domain	658 – 1114	Cytoplasmic
Modified residue	1062 – 1062	Phosphotyrosine; by autocatalysis
Mutagenesis	708 – 1114	Missing. Loss of induced cell death, but increased cell aggregation.
Mutagenesis	1062 – 1062	Y -> F. Abolishes GFRAL-mediated MAPK1/MAPK2 phosphorylation.

Literature citations

Mutations in three genes are found associated with the development of Hirschsprung disease: RET, EDNRB and EDN3.
Hofstra R.M.W.; Osinga J.; Stulp R.P.; Scheffer H.; Meijers C.; Buys C.H.C.M.;
Cited for: VARIANTS HSCR1 TYR-157; LYS-359; TYR-609; ARG-620; ASN-1059 DEL AND PRO-1061;

Two distinct mutations of the RET receptor causing Hirschsprung's disease impair the binding of signalling effectors to a multifunctional docking site.
Geneste O.; Bidaud C.; De Vita G.; Hofstra R.M.W.; Tartare-Deckert S.; Buys C.H.C.M.; Lenoir G.M.; Santoro M.; Billaud M.;
Hum. Mol. Genet. 8:1989-1999(1999)
Cited for: VARIANTS HSCR1 ASN-1059 DEL AND PRO-1061;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07949: Variant p.Leu1061Pro