Published Functional Data on Missense Changes and Unclassified Variants in BRCA1 and BRCA2


This table was generated from our database on 15-03-2002. We will continue to add references to this database and post updates on this site regularly.

 

Gene

Exon

Designation

Assay used

Interaction tested

Result

Reference

BRCA1

2

V11A

E3 Ub-ligase activity assay

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

2

V11A

Radiation sensitivity

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

2

M18T

Radiation sensitivity

None (BRCA1 feature)

As mutant control

(5)

BRCA1

2

M18T

E3 Ub-ligase activity assay

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

2

I21V

E3 Ub-ligase activity assay

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

2

I21V

Radiation sensitivity

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

2

C24R

E3 Ub-ligase activity assay

None (BRCA1 feature)

As mutant control

(5)

BRCA1

2

C24R

Radiation sensitivity

None (BRCA1 feature)

As mutant control

(5)

BRCA1

3

I31M

E3 Ub-ligase activity assay

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

3

I31M

Radiation sensitivity

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

3

T37R

E3 Ub-ligase activity assay

None (BRCA1 feature)

As mutant control

(5)

BRCA1

3

T37R

Radiation sensitivity

None (BRCA1 feature)

As mutant control

(5)

BRCA1

3

C39A

Gel filtration chromatography

BRCA1/RING-BARD1

As wildtype control

(1)

BRCA1

3

H41A

Gel filtration chromatography

BRCA1/RING-BARD1

As wildtype control

(1)

BRCA1

3

I42V

E3 Ub-ligase activity assay

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

3

I42V

Radiation sensitivity

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

5

C61A

Gel filtration chromatography

BRCA1/RING-BARD1

As wildtype control

(1)

BRCA1

5

C61G

Survival assay with HCC1937 (after MMS treatment)

None (BRCA1 feature)

As mutant control

(7)

BRCA1

5

C64A

Gel filtration chromatography

BRCA1/RING-BARD1

As wildtype control

(1)

BRCA1

5

R71G

E3 Ub-ligase activity assay

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

5

R71G

Radiation sensitivity

None (BRCA1 feature)

As wildtype control

(5)

BRCA1

16

T1561I

Transcription activation in yeast (GAL4-fusions)

None (BRCA1 feature)

As wildtype control

(4)

BRCA1

16

L1564P

Transcription activation in yeast (GAL4-fusions)

None (BRCA1 feature)

As wildtype control

(4)

BRCA1

18

C1697R

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA1

18

R1699W

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA1

18

R1699L

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA1

18

G1706E

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA1

18

A1708E

Proteolytic degradation

None (BRCA1 feature)

As mutant control

(6)

BRCA1

18

A1708E

Survival assay with HCC1937 (after MMS treatment)

None (BRCA1 feature)

As mutant control

(7)

BRCA1

18

S1715R (5264C>A)

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA1

18

W1718C

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA1

20

D1733G

Transcription activation in yeast (GAL4-fusions)

None (BRCA1 feature)

As wildtype control

(4)

BRCA1

20

G1738E

Transcription activation in yeast (GAL4-fusions)

None (BRCA1 feature)

As mutant control

(4)

BRCA1

21

M1775R

Proteolytic degradation

None (BRCA1 feature)

Intermediate mt/wt

(6)

BRCA1

23

P1806A

Transcription activation in yeast (GAL4-fusions)

None (BRCA1 feature)

As wildtype control

(4)

BRCA1

24

W1837G

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA1

24

W1837R

Structural prediction (crystallography)

None (BRCA1 feature)

Predicted deleterious

(6)

BRCA2

11

D1420Y (G>T)

DNA binding assay (gel-shift)

BRCA2/BRC3 domain - Rad51

As wildtype control

(3)

BRCA2

11

T1430A

DNA binding assay (gel-shift)

BRCA2/BRC3 domain - Rad51

As mutant control

(3)

BRCA2

11

G1529R

Yeast two-hybrid

BRCA2-BRC4/RAD51

Intermediate mt/wt

(2)

References

     1.    Brzovic PS, Meza JE, King MC, Klevit RE (2001) BRCA1 RING domain cancer-predisposing mutations - Structural consequences and effects on protein-protein interactions. J Biol Chem, 276: 41399-41406.

     2.    Chen CF, Chen PL, Zhong Q, Sharp ZD, Lee WH (1999) Expression of BRC repeats in breast cancer cells disrupts the BRCA2-Rad51 complex and leads to radiation hypersensitivity and loss of G(2)/M checkpoint control. J Biol Chem, 274: 32931-32935.

     3.    Davies AA, Masson JY, Mcllwraith MJ, Stasiak AZ, Stasiak A, Venkitaraman AR, West SC (2001) Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol Cell, 7: 273-282.

     4.    Hayes F, Cayanan C, Barilla D, Monteiro ANA (2000) Functional assay for BRCA1: Mutagenesis of the COOH- terminal region reveals critical residues for transcription activation. Cancer Res, 60: 2411-2418.

     5.    Ruffner H, Joazeiro CA, Hemmati D, Hunter T, Verma IM (2001) Cancer-predisposing mutations within the RING domain of BRCA1: Loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Proc Natl Acad Sci USA, 98: 5134-5139.

     6.    Williams RS, Green R, Glover JNM (2001) Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. Nature Struct Biol, 8: 838-842.

     7.   Zhong Q, Chen CF, Li S, Chen YM, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (1999) Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science, 285: 747-750.