UniProtKB/Swiss-Prot P38398: Variant p.Leu22Ser

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

Variant position:  22
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 Leucine (L) to Serine (S) at position 22 (L22S, p.Leu22Ser).
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 (L) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.
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 BC.
Any additional useful information about the variant.



Sequence information

Variant position:  22
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:   DLSALRVEEVQNVINAMQKI  L ECPICLELIKEPVSTKCDHI
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                         DLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHI

Gorilla                       DLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHI

Rhesus macaque                DLSAVRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHI

Chimpanzee                    DLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHI

Mouse                         DLSAVQIQEVQNVLHAMQKILECPICLELIKEPVSTKCDHI

Rat                           DLSAVRIQEVQNVLHAMQKILECPICLELIKEPVSTQCDHI

Bovine                        DLSADHVEEVQNVLNAMQKILECPICLELIKEPVSTKCDHI

Dog                           DLSADRVEEVQNVLNAMQKILECPICLELIKEPVSTKCDHI

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
Mutagenesis 26 – 26 I -> A. Disrupts the interaction with E2 enzymes, thereby abolishing the E3 ubiquitin-protein ligase activity.
Mutagenesis 26 – 26 I -> E. No ubiquitination of RBBP8. No restoration RBBP8-mediated focus formation or G2/M checkpoint control upon DNA damage.


Literature citations

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.
Katagiri T.; Kasumi F.; Yoshimoto M.; Nomizu T.; Asaishi K.; Abe R.; Tsuchiya A.; Sugano M.; Takai S.; Yoneda M.; Fukutomi T.; Nanba K.; Makita M.; Okazaki H.; Hirata K.; Okazaki M.; Furutsuma Y.; Morishita Y.; Iino Y.; Karino T.; Ayabe H.; Hara S.; Kajiwara T.; Houga S.; Shimizu T.; Toda M.; Yamazaki Y.; Uchida T.; Kunitomo K.; Sonoo H.; Kurebayashi J.; Shimotsuma K.; Nakamura Y.; Miki Y.;
J. Hum. Genet. 43:42-48(1998)
Cited for: VARIANTS BC SER-22; LEU-461; ASP-465; VAL-552; SER-892; ASP-960; ILE-1025 AND ALA-1047;

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.