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UniProtKB/Swiss-Prot O43502: Variant p.Leu138Phe

DNA repair protein RAD51 homolog 3
Gene: RAD51C
Variant information

Variant position:  138
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Leucine (L) to Phenylalanine (F) at position 138 (L138F, p.Leu138Phe).
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 large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 BROVCA3; reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51.
Any additional useful information about the variant.

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



Sequence information

Variant position:  138
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  376
The length of the canonical sequence.

Location on the sequence:   MKTTEICGAPGVGKTQLCMQ  L AVDVQIPECFGGVAGEAVFI
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                         MKTTEICGAPGVGKTQLCMQLAVDVQIPECFGGVAGEAVFI

Mouse                         MKTTEVCGVPGVGKTQLCMQLAVDVQIPECFGGVAGEAVFI

Slime mold                    KKITEICGVPGIGKTNMAFQLLVNTSIPFDLGGVQGKAIYI

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 – 376 DNA repair protein RAD51 homolog 3
Alternative sequence 135 – 135 C -> W. In isoform 2.
Alternative sequence 136 – 376 Missing. In isoform 2.
Mutagenesis 131 – 131 K -> A. Significant loss of function; abolishes Holliday junction resolution activity.
Mutagenesis 131 – 131 K -> R. Partial loss of function.


Literature citations

Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair.
Park J.Y.; Singh T.R.; Nassar N.; Zhang F.; Freund M.; Hanenberg H.; Meetei A.R.; Andreassen P.R.;
Oncogene 33:4803-4812(2014)
Cited for: INTERACTION WITH BRCA2; RAD51 AND PALB2; IDENTIFICATION IN A PALB2-CONTAINING HR COMPLEX; CHARACTERIZATION OF VARIANT BROVCA3 PHE-138; CHARACTERIZATION OF VARIANT ASN-159; CHARACTERIZATION OF VARIANT FANCO HIS-258;

Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene.
Meindl A.; Hellebrand H.; Wiek C.; Erven V.; Wappenschmidt B.; Niederacher D.; Freund M.; Lichtner P.; Hartmann L.; Schaal H.; Ramser J.; Honisch E.; Kubisch C.; Wichmann H.E.; Kast K.; Deissler H.; Engel C.; Muller-Myhsok B.; Neveling K.; Kiechle M.; Mathew C.G.; Schindler D.; Schmutzler R.K.; Hanenberg H.;
Nat. Genet. 42:410-414(2010)
Cited for: VARIANTS ARG-3; THR-126; ASN-159; ALA-169; SER-264; VAL-264; ALA-287 AND GLN-366; VARIANTS BROVCA3 VAL-125 AND PHE-138;

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.