UniProtKB/Swiss-Prot P07333: Variant p.Met766Thr

Macrophage colony-stimulating factor 1 receptor
Gene: CSF1R
Chromosomal location: 5q33-q35
Variant information

Variant position:  766
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Methionine (M) to Threonine (T) at position 766 (M766T, p.Met766Thr).
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 (M) 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

Variant description:  In HDLS; impairs autophosphorylation upon stimulation with CSF1.
Any additional useful information about the variant.



Sequence information

Variant position:  766
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  972
The length of the canonical sequence.

Location on the sequence:   DGRPLELRDLLHFSSQVAQG  M AFLASKNCIHRDVAARNVLL
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                         DGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLL

Mouse                         ASRPLELWDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLL

Rat                           PSRPLELWDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLL

Cat                           DGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLL

Zebrafish                     DSWPLDMDDLLRFSSQVAQGLDFLAAKNCIHRDVAARNVLL

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 20 – 972 Macrophage colony-stimulating factor 1 receptor
Topological domain 539 – 972 Cytoplasmic
Domain 582 – 910 Protein kinase
Active site 778 – 778 Proton acceptor
Alternative sequence 307 – 972 Missing. In isoform 2.
Helix 753 – 771


Literature citations

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.
Rademakers R.; Baker M.; Nicholson A.M.; Rutherford N.J.; Finch N.; Soto-Ortolaza A.; Lash J.; Wider C.; Wojtas A.; DeJesus-Hernandez M.; Adamson J.; Kouri N.; Sundal C.; Shuster E.A.; Aasly J.; MacKenzie J.; Roeber S.; Kretzschmar H.A.; Boeve B.F.; Knopman D.S.; Petersen R.C.; Cairns N.J.; Ghetti B.; Spina S.; Garbern J.; Tselis A.C.; Uitti R.; Das P.; Van Gerpen J.A.; Meschia J.F.; Levy S.; Broderick D.F.; Graff-Radford N.; Ross O.A.; Miller B.B.; Swerdlow R.H.; Dickson D.W.; Wszolek Z.K.;
Nat. Genet. 44:200-205(2012)
Cited for: VARIANTS HDLS 774-CYS--ASN-814 DEL; 585-GLY--LYS-619 DELINS ALA; GLU-589; LYS-633; THR-766; PRO-770; ASN-775; THR-794; TYR-837; SER-849; PHE-849 DEL; PRO-868; THR-875 AND THR-878; VARIANTS HIS-710; ARG-747 AND ASP-920; CHARACTERIZATION OF VARIANTS HDLS LYS-633; THR-766 AND THR-875;

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.