UniProtKB/Swiss-Prot P38398: Variant p.Cys64Gly

Breast cancer type 1 susceptibility protein
Gene: BRCA1
Chromosomal location: 17q21
Variant information

Variant position:  64
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 Cysteine (C) to Glycine (G) at position 64 (C64G, p.Cys64Gly).
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 polar (C) to glycine (G)
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 BC; no interaction with BAP1.
Any additional useful information about the variant.



Sequence information

Variant position:  64
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1863
The length of the canonical sequence.

Location on the sequence:   CKFCMLKLLNQKKGPSQCPL  C KNDITKRSLQESTRFSQLVE
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                         CKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVE

Gorilla                       CKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVE

Rhesus macaque                CRFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVE

Chimpanzee                    CKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVE

Mouse                         CKFCMLKLLNQKKGPSQCPLCKNEITKRSLQGSTRFSQLAE

Rat                           CKFCMLKLLNQKKGPSQCPLCKNEITKRSLQGSARFSQLVE

Bovine                        CKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVE

Dog                           CKFCMLKLLNQRKGPSQCPLCKNDITKRSLQESTRFSQLVE

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 1 – 1863 Breast cancer type 1 susceptibility protein
Zinc finger 24 – 65 RING-type
Alternative sequence 64 – 1863 Missing. In isoform 2.
Mutagenesis 71 – 71 R -> G. No effect on interaction with BAP1.
Turn 62 – 64


Literature citations

BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression.
Jensen D.E.; Proctor M.; Marquis S.T.; Gardner H.P.; Ha S.I.; Chodosh L.A.; Ishov A.M.; Tommerup N.; Vissing H.; Sekido Y.; Minna J.; Borodovsky A.; Schultz D.C.; Wilkinson K.D.; Maul G.G.; Barlev N.; Berger S.; Prendergast G.C.; Rauscher F.J. III;
Oncogene 16:1097-1112(1998)
Cited for: INTERACTION WITH BAP1; SUBCELLULAR LOCATION; VARIANTS GLY-61 AND GLY-64; MUTAGENESIS OF ARG-71;

Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer.
Castilla L.H.; Couch F.J.; Erdos M.R.; Hoskins K.F.; Calzone K.; Garber J.E.; Boyd J.; Lubin M.B.; Deshano M.L.; Brody L.C.; Collins F.S.; Weber B.L.;
Nat. Genet. 8:387-391(1994)
Cited for: VARIANT BC GLY-64; VARIANTS ALA-772; ASN-1040 AND GLY-1443;

Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation screening.
Andersen T.I.; Eiken H.G.; Couch F.; Kaada G.; Skrede M.; Johnsen H.; Aloysius T.A.; Tveit K.M.; Tranebjaerg L.; Doerum A.; Moeller P.; Weber B.L.; Boerresen-Dale A.-L.;
Hum. Mutat. 11:166-174(1998)
Cited for: VARIANT BC GLY-64; VARIANTS ALA-772; GLU-820; ASN-1040; GLY-1443; ILE-1512; LEU-1637 AND ILE-1652;

A high-throughput functional complementation assay for classification of BRCA1 missense variants.
Bouwman P.; van der Gulden H.; van der Heijden I.; Drost R.; Klijn C.N.; Prasetyanti P.; Pieterse M.; Wientjens E.; Seibler J.; Hogervorst F.B.; Jonkers J.;
Cancer Discov. 3:1142-1155(2013)
Cited for: CHARACTERIZATION OF VARIANTS BC PHE-4; THR-18; GLN-45; GLY-61; GLY-64; TYR-67; LYS-132; HIS-142; PHE-147; PRO-165; TRP-170; TYR-186; ILE-191; MET-231; VAL-245; VAL-246; LEU-271; PHE-668; ASN-695; LEU-798; TYR-810; LYS-826; GLN-841; HIS-856; ASN-1101; ASN-1140; GLY-1140; LYS-1214; LYS-1236; SER-1267; VAL-1282; SER-1297 DEL; ARG-1301; LYS-1346; ILE-1378; VAL-1400; PRO-1407; THR-1411; GLY-1443; GLY-1448; CYS-1486; MET-1534; PRO-1589; THR-1628; PRO-1651; PHE-1651; PHE-1655; ARG-1686; GLN-1686; VAL-1688 DEL; ILE-1691; TRP-1699; GLN-1699; GLU-1706; ALA-1706; GLU-1708; CYS-1718; ALA-1720; LYS-1735; ALA-1736; GLY-1739; VAL-1739; GLN-1746; THR-1753; PRO-1764; SER-1767; VAL-1770; CYS-1782; THR-1789; ASP-1794; ASP-1804; ARG-1812; ARG-1837 AND LEU-1862; VARIANTS CYS-105; CYS-866; ALA-1060; LYS-1250 AND ILE-1652;

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.