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UniProtKB/Swiss-Prot Q86YC2: Variant p.Leu35Pro

Partner and localizer of BRCA2
Gene: PALB2
Variant information

Variant position:  35
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 Leucine (L) to Proline (P) at position 35 (L35P, p.Leu35Pro).
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

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. {ECO:0000269|PubMed:17287723, ECO:0000269|PubMed:22241545, ECO:0000269|PubMed:28319063}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Breast cancer susceptibility is strongly associated with PALB2 truncating mutations. Conversely, rare missense mutations do not strongly influence breast cancer risk (PubMed:22241545). {ECO:0000269|PubMed:22241545}.
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; abrogates the interaction with BRCA1; abrogates double-stranded DNA break-initiated homologous recombination; abrogates PALB2 and RAD51 localization to ionizing radiation-induced foci; may weaken homooligomerization.
Any additional useful information about the variant.

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

Sequence information

Variant position:  35
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1186
The length of the canonical sequence.

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.



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.

Chain 1 – 1186 Partner and localizer of BRCA2
Region 1 – 579 DNA-binding (with the preference D loop > dsDNA > ssDNA)
Region 1 – 319 Interaction with BRCA1
Region 1 – 200 Interaction with RAD51
Region 1 – 160 Required for its oligomerization and is important for its focal concentration at DNA damage sites
Coiled coil 9 – 41
Mutagenesis 21 – 21 L -> A. Loss of interaction with BRCA1 but no effect on interaction with BRCA2.
Mutagenesis 28 – 28 Y -> A. Loss of interaction with BRCA1 but no effect on interaction with BRCA2.
Mutagenesis 35 – 35 L -> A. Loss of interaction with BRCA1 but no effect on interaction with BRCA2.
Mutagenesis 42 – 42 E -> A. Loss of interaction with BRCA1 but no effect on interaction with BRCA2.

Literature citations

Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.
Foo T.K.; Tischkowitz M.; Simhadri S.; Boshari T.; Zayed N.; Burke K.A.; Berman S.H.; Blecua P.; Riaz N.; Huo Y.; Ding Y.C.; Neuhausen S.L.; Weigelt B.; Reis-Filho J.S.; Foulkes W.D.; Xia B.;
Oncogene 36:4161-4170(2017)

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.