UniProtKB/Swiss-Prot Q9HCK4: Variant p.Ile945Thr

Roundabout homolog 2
Gene: ROBO2
Chromosomal location: 3p12.3
Variant information

Variant position:  945
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 Isoleucine (I) to Threonine (T) at position 945 (I945T, p.Ile945Thr).
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 medium size and hydrophobic (I) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Vesicoureteral reflux 2 (VUR2) [MIM:610878]: A disease belonging to the group of congenital anomalies of the kidney and urinary tract. It is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys, and is a risk factor for urinary tract infections. Primary disease results from a developmental defect of the ureterovesical junction. In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy. Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, renal insufficiency and end-stage renal disease. {ECO:0000269|PubMed:17357069}. 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 VUR2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  945
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1378
The length of the canonical sequence.

Location on the sequence:   ADSWPATSLPVNNSNSGPNE  I GNFGRGDVLPPVPGQGDKTA
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                         ADSWPATSLPVNNSNSGPNEIGNFGRGDVLPPVPGQGDKTA

Mouse                         ADSWPATSLPVNNSNSGPNEIGNFGRGDVLPPVPGQGDKTA

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 22 – 1378 Roundabout homolog 2
Topological domain 881 – 1378 Cytoplasmic


Literature citations

Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux.
Lu W.; van Eerde A.M.; Fan X.; Quintero-Rivera F.; Kulkarni S.; Ferguson H.; Kim H.-G.; Fan Y.; Xi Q.; Li Q.-G.; Sanlaville D.; Andrews W.; Sundaresan V.; Bi W.; Yan J.; Giltay J.C.; Wijmenga C.; de Jong T.P.V.M.; Feather S.A.; Woolf A.S.; Rao Y.; Lupski J.R.; Eccles M.R.; Quade B.J.; Gusella J.F.; Morton C.C.; Maas R.L.;
Am. J. Hum. Genet. 80:616-632(2007)
Cited for: VARIANTS VUR2 THR-945 AND THR-1236; CHROMOSOMAL TRANSLOCATION WITH PCDH11Y;

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.