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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.

This is an interactive structure display. Feel free to play with it after the tour!

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

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Summary

ATM - ENST00000278616

Gene ATM - ENSG00000149311 | ENSP00000278616 | ENST00000278616
Ensembl | RefSeq | UniProt
Location GRCh38 11:108222832-108369099 Ensembl UCSC
Description ATM serine/threonine kinase

Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. {ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871}.;

Condition(s)
  • Ataxia telangiectasia (AT)

    A rare recessive disorder characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. Patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation.
    The disease is caused by mutations affecting the gene represented in this entry. OMIM

    MedGen: C0004135 C1458155 C0950123 C0677776 C0017636 OrphaNet: 100 360 180250 145

Sequence
MSLVLNDLLI
10
CCRQLEHDRA
20
TERKKEVEKF
30
KRLIRDPETI
40
KHLDRHSDSK
50
QGKYLNWDAV
60
FRFLQKYIQK
70
ETECLRIAKP
80
NVSASTQASR
90
QKKMQEISSL
100
VKYFIKCANR
110
RAPRLKCQEL
120
LNYIMDTVKD
130
SSNGAIYGAD
140
CSNILLKDIL
150
SVRKYWCEIS
160
QQQWLELFSV
170
YFRLYLKPSQ
180
DVHRVLVARI
190
IHAVTKGCCS
200
QTDGLNSKFL
210
DFFSKAIQCA
220
RQEKSSSGLN
230
HILAALTIFL
240
KTLAVNFRIR
250
VCELGDEILP
260
TLLYIWTQHR
270
LNDSLKEVII
280
ELFQLQIYIH
290
HPKGAKTQEK
300
GAYESTKWRS
310
ILYNLYDLLV
320
NEISHIGSRG
330
KYSSGFRNIA
340
VKENLIELMA
350
DICHQVFNED
360
TRSLEISQSY
370
TTTQRESSDY
380
SVPCKRKKIE
390
LGWEVIKDHL
400
QKSQNDFDLV
410
PWLQIATQLI
420
SKYPASLPNC
430
ELSPLLMILS
440
QLLPQQRHGE
450
RTPYVLRCLT
460
EVALCQDKRS
470
NLESSQKSDL
480
LKLWNKIWCI
490
TFRGISSEQI
500
QAENFGLLGA
510
IIQGSLVEVD
520
REFWKLFTGS
530
ACRPSCPAVC
540
CLTLALTTSI
550
VPGTVKMGIE
560
QNMCEVNRSF
570
SLKESIMKWL
580
LFYQLEGDLE
590
NSTEVPPILH
600
SNFPHLVLEK
610
ILVSLTMKNC
620
KAAMNFFQSV
630
PECEHHQKDK
640
EELSFSEVEE
650
LFLQTTFDKM
660
DFLTIVRECG
670
IEKHQSSIGF
680
SVHQNLKESL
690
DRCLLGLSEQ
700
LLNNYSSEIT
710
NSETLVRCSR
720
LLVGVLGCYC
730
YMGVIAEEEA
740
YKSELFQKAK
750
SLMQCAGESI
760
TLFKNKTNEE
770
FRIGSLRNMM
780
QLCTRCLSNC
790
TKKSPNKIAS
800
GFFLRLLTSK
810
LMNDIADICK
820
SLASFIKKPF
830
DRGEVESMED
840
DTNGNLMEVE
850
DQSSMNLFND
860
YPDSSVSDAN
870
EPGESQSTIG
880
AINPLAEEYL
890
SKQDLLFLDM
900
LKFLCLCVTT
910
AQTNTVSFRA
920
ADIRRKLLML
930
IDSSTLEPTK
940
SLHLHMYLML
950
LKELPGEEYP
960
LPMEDVLELL
970
KPLSNVCSLY
980
RRDQDVCKTI
990
LNHVLHVVKN
1000
LGQSNMDSEN
1010
TRDAQGQFLT
1020
VIGAFWHLTK
1030
ERKYIFSVRM
1040
ALVNCLKTLL
1050
EADPYSKWAI
1060
LNVMGKDFPV
1070
NEVFTQFLAD
1080
NHHQVRMLAA
1090
ESINRLFQDT
1100
KGDSSRLLKA
1110
LPLKLQQTAF
1120
ENAYLKAQEG
1130
MREMSHSAEN
1140
PETLDEIYNR
1150
KSVLLTLIAV
1160
VLSCSPICEK
1170
QALFALCKSV
1180
KENGLEPHLV
1190
KKVLEKVSET
1200
FGYRRLEDFM
1210
ASHLDYLVLE
1220
WLNLQDTEYN
1230
LSSFPFILLN
1240
YTNIEDFYRS
1250
CYKVLIPHLV
1260
IRSHFDEVKS
1270
IANQIQEDWK
1280
SLLTDCFPKI
1290
LVNILPYFAY
1300
EGTRDSGMAQ
1310
QRETATKVYD
1320
MLKSENLLGK
1330
QIDHLFISNL
1340
PEIVVELLMT
1350
LHEPANSSAS
1360
QSTDLCDFSG
1370
DLDPAPNPPH
1380
FPSHVIKATF
1390
AYISNCHKTK
1400
LKSILEILSK
1410
SPDSYQKILL
1420
AICEQAAETN
1430
NVYKKHRILK
1440
IYHLFVSLLL
1450
KDIKSGLGGA
1460
WAFVLRDVIY
1470
TLIHYINQRP
1480
SCIMDVSLRS
1490
FSLCCDLLSQ
1500
VCQTAVTYCK
1510
DALENHLHVI
1520
VGTLIPLVYE
1530
QVEVQKQVLD
1540
LLKYLVIDNK
1550
DNENLYITIK
1560
LLDPFPDHVV
1570
FKDLRITQQK
1580
IKYSRGPFSL
1590
LEEINHFLSV
1600
SVYDALPLTR
1610
LEGLKDLRRQ
1620
LELHKDQMVD
1630
IMRASQDNPQ
1640
DGIMVKLVVN
1650
LLQLSKMAIN
1660
HTGEKEVLEA
1670
VGSCLGEVGP
1680
IDFSTIAIQH
1690
SKDASYTKAL
1700
KLFEDKELQW
1710
TFIMLTYLNN
1720
TLVEDCVKVR
1730
SAAVTCLKNI
1740
LATKTGHSFW
1750
EIYKMTTDPM
1760
LAYLQPFRTS
1770
RKKFLEVPRF
1780
DKENPFEGLD
1790
DINLWIPLSE
1800
NHDIWIKTLT
1810
CAFLDSGGTK
1820
CEILQLLKPM
1830
CEVKTDFCQT
1840
VLPYLIHDIL
1850
LQDTNESWRN
1860
LLSTHVQGFF
1870
TSCLRHFSQT
1880
SRSTTPANLD
1890
SESEHFFRCC
1900
LDKKSQRTML
1910
AVVDYMRRQK
1920
RPSSGTIFND
1930
AFWLDLNYLE
1940
VAKVAQSCAA
1950
HFTALLYAEI
1960
YADKKSMDDQ
1970
EKRSLAFEEG
1980
SQSTTISSLS
1990
EKSKEETGIS
2000
LQDLLLEIYR
2010
SIGEPDSLYG
2020
CGGGKMLQPI
2030
TRLRTYEHEA
2040
MWGKALVTYD
2050
LETAIPSSTR
2060
QAGIIQALQN
2070
LGLCHILSVY
2080
LKGLDYENKD
2090
WCPELEELHY
2100
QAAWRNMQWD
2110
HCTSVSKEVE
2120
GTSYHESLYN
2130
ALQSLRDREF
2140
STFYESLKYA
2150
RVKEVEEMCK
2160
RSLESVYSLY
2170
PTLSRLQAIG
2180
ELESIGELFS
2190
RSVTHRQLSE
2200
VYIKWQKHSQ
2210
LLKDSDFSFQ
2220
EPIMALRTVI
2230
LEILMEKEMD
2240
NSQRECIKDI
2250
LTKHLVELSI
2260
LARTFKNTQL
2270
PERAIFQIKQ
2280
YNSVSCGVSE
2290
WQLEEAQVFW
2300
AKKEQSLALS
2310
ILKQMIKKLD
2320
ASCAANNPSL
2330
KLTYTECLRV
2340
CGNWLAETCL
2350
ENPAVIMQTY
2360
LEKAVEVAGN
2370
YDGESSDELR
2380
NGKMKAFLSL
2390
ARFSDTQYQR
2400
IENYMKSSEF
2410
ENKQALLKRA
2420
KEEVGLLREH
2430
KIQTNRYTVK
2440
VQRELELDEL
2450
ALRALKEDRK
2460
RFLCKAVENY
2470
INCLLSGEEH
2480
DMWVFRLCSL
2490
WLENSGVSEV
2500
NGMMKRDGMK
2510
IPTYKFLPLM
2520
YQLAARMGTK
2530
MMGGLGFHEV
2540
LNNLISRISM
2550
DHPHHTLFII
2560
LALANANRDE
2570
FLTKPEVARR
2580
SRITKNVPKQ
2590
SSQLDEDRTE
2600
AANRIICTIR
2610
SRRPQMVRSV
2620
EALCDAYIIL
2630
ANLDATQWKT
2640
QRKGINIPAD
2650
QPITKLKNLE
2660
DVVVPTMEIK
2670
VDHTGEYGNL
2680
VTIQSFKAEF
2690
RLAGGVNLPK
2700
IIDCVGSDGK
2710
ERRQLVKGRD
2720
DLRQDAVMQQ
2730
VFQMCNTLLQ
2740
RNTETRKRKL
2750
TICTYKVVPL
2760
SQRSGVLEWC
2770
TGTVPIGEFL
2780
VNNEDGAHKR
2790
YRPNDFSAFQ
2800
CQKKMMEVQK
2810
KSFEEKYEVF
2820
MDVCQNFQPV
2830
FRYFCMEKFL
2840
DPAIWFEKRL
2850
AYTRSVATSS
2860
IVGYILGLGD
2870
RHVQNILINE
2880
QSAELVHIDL
2890
GVAFEQGKIL
2900
PTPETVPFRL
2910
TRDIVDGMGI
2920
TGVEGVFRRC
2930
CEKTMEVMRN
2940
SQETLLTIVE
2950
VLLYDPLFDW
2960
TMNPLKALYL
2970
QQRPEDETEL
2980
HPTLNADDQE
2990
CKRNLSDIDQ
3000
SFNKVAERVL
3010
MRLQEKLKGV
3020
EEGTVLSVGG
3030
QVNLLIQQAI
3040
DPKNLSRLFP
3050
GWKAWV
3056
PDB and PDB position 5np1 ~> 2227 (Explore)
gnomAD This variant is not present in gnomAD .
Pathogenicity pathogenic according to Clinvar
Literature for Arg2227 in ATM Not present
Literature for similar variants in homologous proteins Not present
Older predictions

Literature

Literature for Arg2227Cys in ATM

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: pathogenic according to Clinvar

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

Helix prediction details

Prediction: benign 41%

The Arg2227Cys mutation in the protein has been classified as benign by our ensemble classifier system, with baseline confidence. There is a 69% 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

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

Evolutionary pressure

Conservation

The wildtype was observed in 83.08% of the 1005 sequences analyzed. The variant type was observed in < 1% of observed sequences.


This residue is involved in 1 CationPi interaction, 2 Hydrogen Bonds and 7 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.