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Here you can see the gene and the variant being analyzed.

We summarize a large amount of clinical data on this gene here. Links are added where available to source information.

Prediction information is summarized here, the percentage shows the likelihood that the variant is pathogenic.

Agreement is a measure (out of 5 stars) of how much our predictors agree between each other. When predictors agree, the prediction is more likely to be correct.

Data quality is a measure (out of 5 stars) of how good the underlying data for this prediction is. This is an assessment of the depth of our alignments and the number of structures available, among other factors.

This table shows literature for this exact position and protein, if it is available.

This table shows literature for this position in homologous proteins, if it is available.

This is a description of our prediction.

This plot illustrates the agreement between different classifiers. If the prediction distributions align on one side it indicates increased certainty in the prediction.

This describes the data quality for this position.

Here are the four factors that contributed most to the prediction. Factors that contributed to a benign prediction are colored blue, pathogenic factors are colored red.

This plot shows all the factors for prediction. Factors that contributed to a benign prediction are colored blue, pathogenic factors are colored red.

This plot shows the conservation on this position.

Here the conservation statistics are described.

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This is a list of interactions we found for this position.

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Summary

BRCA1 - ENST00000357654

Gene BRCA1 - ENSG00000012048 | ENSP00000350283 | ENST00000357654
Ensembl | RefSeq | UniProt
Location GRCh38 17:43044295-43125483 Ensembl UCSC
Description BRCA1, DNA repair associated

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator

Condition(s)
  • Breast-ovarian cancer, familial, 1 (BROVCA1)

    A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. OMIM

    MedGen: C0678222 C1458155 C1140680 C2676676 C0677776 C0006142 C0027672 OrphaNet: 180250 145 213500 227535

  • Breast cancer (BC)

    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.
    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. OMIM

    MedGen: C0677776 C0006142 C1458155 C0678222 OrphaNet: 180250 145 227535

  • Pancreatic cancer 4 (PNCA4)

    A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. OMIM

    MedGen: C0027672

  • Fanconi anemia, complementation group S (FANCS)

    A form of Fanconi anemia, a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. OMIM

    MedGen: C2676676 C0027672 C1140680

  • Ovarian cancer (OC)

    The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
    Disease susceptibility is associated with variations affecting the gene represented in this entry. OMIM

    MedGen: C0919267 OrphaNet: 145

Sequence
MDLSALRVEE
10
VQNVINAMQK
20
ILECPICLEL
30
IKEPVSTKCD
40
HIFCKFCMLK
50
LLNQKKGPSQ
60
CPLCKNDITK
70
RSLQESTRFS
80
QLVEELLKII
90
CAFQLDTGLE
100
YANSYNFAKK
110
ENNSPEHLKD
120
EVSIIQSMGY
130
RNRAKRLLQS
140
EPENPSLQET
150
SLSVQLSNLG
160
TVRTLRTKQR
170
IQPQKTSVYI
180
ELGSDSSEDT
190
VNKATYCSVG
200
DQELLQITPQ
210
GTRDEISLDS
220
AKKAACEFSE
230
TDVTNTEHHQ
240
PSNNDLNTTE
250
KRAAERHPEK
260
YQGSSVSNLH
270
VEPCGTNTHA
280
SSLQHENSSL
290
LLTKDRMNVE
300
KAEFCNKSKQ
310
PGLARSQHNR
320
WAGSKETCND
330
RRTPSTEKKV
340
DLNADPLCER
350
KEWNKQKLPC
360
SENPRDTEDV
370
PWITLNSSIQ
380
KVNEWFSRSD
390
ELLGSDDSHD
400
GESESNAKVA
410
DVLDVLNEVD
420
EYSGSSEKID
430
LLASDPHEAL
440
ICKSERVHSK
450
SVESNIEDKI
460
FGKTYRKKAS
470
LPNLSHVTEN
480
LIIGAFVTEP
490
QIIQERPLTN
500
KLKRKRRPTS
510
GLHPEDFIKK
520
ADLAVQKTPE
530
MINQGTNQTE
540
QNGQVMNITN
550
SGHENKTKGD
560
SIQNEKNPNP
570
IESLEKESAF
580
KTKAEPISSS
590
ISNMELELNI
600
HNSKAPKKNR
610
LRRKSSTRHI
620
HALELVVSRN
630
LSPPNCTELQ
640
IDSCSSSEEI
650
KKKKYNQMPV
660
RHSRNLQLME
670
GKEPATGAKK
680
SNKPNEQTSK
690
RHDSDTFPEL
700
KLTNAPGSFT
710
KCSNTSELKE
720
FVNPSLPREE
730
KEEKLETVKV
740
SNNAEDPKDL
750
MLSGERVLQT
760
ERSVESSSIS
770
LVPGTDYGTQ
780
ESISLLEVST
790
LGKAKTEPNK
800
CVSQCAAFEN
810
PKGLIHGCSK
820
DNRNDTEGFK
830
YPLGHEVNHS
840
RETSIEMEES
850
ELDAQYLQNT
860
FKVSKRQSFA
870
PFSNPGNAEE
880
ECATFSAHSG
890
SLKKQSPKVT
900
FECEQKEENQ
910
GKNESNIKPV
920
QTVNITAGFP
930
VVGQKDKPVD
940
NAKCSIKGGS
950
RFCLSSQFRG
960
NETGLITPNK
970
HGLLQNPYRI
980
PPLFPIKSFV
990
KTKCKKNLLE
1000
ENFEEHSMSP
1010
EREMGNENIP
1020
STVSTISRNN
1030
IRENVFKEAS
1040
SSNINEVGSS
1050
TNEVGSSINE
1060
IGSSDENIQA
1070
ELGRNRGPKL
1080
NAMLRLGVLQ
1090
PEVYKQSLPG
1100
SNCKHPEIKK
1110
QEYEEVVQTV
1120
NTDFSPYLIS
1130
DNLEQPMGSS
1140
HASQVCSETP
1150
DDLLDDGEIK
1160
EDTSFAENDI
1170
KESSAVFSKS
1180
VQKGELSRSP
1190
SPFTHTHLAQ
1200
GYRRGAKKLE
1210
SSEENLSSED
1220
EELPCFQHLL
1230
FGKVNNIPSQ
1240
STRHSTVATE
1250
CLSKNTEENL
1260
LSLKNSLNDC
1270
SNQVILAKAS
1280
QEHHLSEETK
1290
CSASLFSSQC
1300
SELEDLTANT
1310
NTQDPFLIGS
1320
SKQMRHQSES
1330
QGVGLSDKEL
1340
VSDDEERGTG
1350
LEENNQEEQS
1360
MDSNLGEAAS
1370
GCESETSVSE
1380
DCSGLSSQSD
1390
ILTTQQRDTM
1400
QHNLIKLQQE
1410
MAELEAVLEQ
1420
HGSQPSNSYP
1430
SIISDSSALE
1440
DLRNPEQSTS
1450
EKAVLTSQKS
1460
SEYPISQNPE
1470
GLSADKFEVS
1480
ADSSTSKNKE
1490
PGVERSSPSK
1500
CPSLDDRWYM
1510
HSCSGSLQNR
1520
NYPSQEELIK
1530
VVDVEEQQLE
1540
ESGPHDLTET
1550
SYLPRQDLEG
1560
TPYLESGISL
1570
FSDDPESDPS
1580
EDRAPESARV
1590
GNIPSSTSAL
1600
KVPQLKVAES
1610
AQSPAAAHTT
1620
DTAGYNAMEE
1630
SVSREKPELT
1640
ASTERVNKRM
1650
SMVVSGLTPE
1660
EFMLVYKFAR
1670
KHHITLTNLI
1680
TEETTHVVMK
1690
TDAEFVCERT
1700
LKYFLGIAGG
1710
KWVVSYFWVT
1720
QSIKERKMLN
1730
EHDFEVRGDV
1740
VNGRNHQGPK
1750
RARESQDRKI
1760
FRGLEICCYG
1770
PFTNMPTDQL
1780
EWMVQLCGAS
1790
VVKELSSFTL
1800
GTGVHPIVVV
1810
QPDAWTEDNG
1820
FHAIGQMCEA
1830
PVVTREWVLD
1840
SVALYQCQEL
1850
DTYLIPQIPH
1860
SHY
1863
PDB and PDB position 4y2g ~> 1720 (Explore)
gnomAD Exome Allele Frequency: 0.00017531
Genome Allele Frequency: 0.0001273723
gnomAD
Pathogenicity benign according to VKGL
Literature for Thr1720 in BRCA1 Not present
Literature for similar variants in homologous proteins Not present
Older predictions

Literature

Literature for Thr1720Ala in BRCA1

There is no literature available for this specific variant


Literature for similar variants in homologous proteins

There is no literature available for variants in a homologous proteins

Helix classification

Classification: benign according to VKGL

This variant was found in the VKGL dataset. According to this authoritative source this variant is classified as benign. A prediction is available for this variant, but this source takes precedence in our classification.

Helix prediction details

Prediction: benign 15%

The Thr1720Ala mutation in the protein has been classified as benign by our ensemble classifier system, with high confidence. There is a 83% agreement between all subclassifiers.

Data quality

Data quality for this region is considered good. This means that enhanced, deep alignments are present and there is a variety of data for the algorithm to predict from.

Prediction factors

External models have estimated which sets of features contributed primarily to the classification. These sets of features are listed here.

Primary contributing factors

  • Position features point towards pathogenic
  • Protein evolutionary pressure points towards pathogenic
  • Residue differences point towards benign
  • Gene vulnerability points towards pathogenic

Evolutionary pressure

Conservation

The wildtype was observed in 43.89% of the 998 sequences analyzed. The variant type was observed in 1.10% of observed sequences.


This residue is involved in 2 Hydrogen Bonds, 3 Hydrophobic interactions.

Interaction statistics were calculated using advanced molecular optimization techniques and may not be visible in the plain PDB file. Please download the YASARA scene to explore the interactions in more detail.