ATM Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human ATM — a definitive lookup resource covering: ### Section …

Provide a comprehensive cross-database identifier and functional mapping reference for human ATM — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene ATM, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene ATM, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene ATM protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene ATM protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene ATM, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene ATM, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene ATM, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene ATM protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene ATM, summarize transcription factor regulatory data. If ATM is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate ATM — names with evidence type (ChIP-seq / predicted / experimentally validated) If ATM is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene ATM protein as a drug target, summarize pharmacology data. If ATM is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If ATM is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene ATM, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene ATM, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in ATM: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

ATM

Executive summary

ATM (Ataxia Telangiectasia Mutated, HGNC:795) is a serine-protein kinase and master regulator of the DNA damage response, encoded on chromosome 11 and best known as the gene mutated in ataxia-telangiectasia, an autosomal recessive condition combining cerebellar ataxia, telangiectasia, immunodeficiency, and severe cancer predisposition. Biallelic loss-of-function is the cause of ataxia-telangiectasia, while heterozygous variants confer elevated risk for breast cancer, prostate cancer, and other malignancies. The protein sits at the apex of the double-strand break signaling cascade, phosphorylating key effectors including CHEK2, BRCA1, H2AX, MDC1, and TP53 (STRING scores 999–975), and participates in 28 Reactome pathways spanning homologous recombination, NHEJ, G2/M checkpoint, and TP53 regulation. ClinVar harbors approximately 18,200 variant submissions, dominated by ~12,000 variants of uncertain significance alongside ~3,000 pathogenic entries, and AlphaMissense flags over 3,000 likely pathogenic missense changes. ATM is an active therapeutic target, with dedicated inhibitors such as AZD-0156 and combination agents including berzosertib (23 trials) and nedisertib (18 trials) in Phase 1–2 oncology trials.

ATM — Reference

Cross-database identifier and functional mapping reference for ATM.

Gene identifiers

FieldValue
Approved symbolATM
HGNC IDHGNC:795
Ensembl gene IDENSG00000149311
NCBI Entrez Gene ID472
OMIM ID607585
Chromosome11
Start position108,222,804
End position108,369,102
Strand+
Genome buildGRCh38

Transcript identifiers

Ensembl Transcripts (ENST)

Total: 64 transcripts

ENST IDBiotype
ENST00000278616protein_coding
ENST00000419286protein_coding_CDS_not_defined
ENST00000452508protein_coding
ENST00000524792retained_intron
ENST00000525012protein_coding_CDS_not_defined
ENST00000525056retained_intron
ENST00000525178protein_coding_CDS_not_defined
ENST00000525537retained_intron
ENST00000526567protein_coding
ENST00000527181retained_intron
ENST00000527389retained_intron
ENST00000527805nonsense_mediated_decay
ENST00000529588nonsense_mediated_decay
ENST00000530958protein_coding
ENST00000531525protein_coding
ENST00000532765protein_coding_CDS_not_defined
ENST00000532931protein_coding
ENST00000533526protein_coding_CDS_not_defined
ENST00000533690retained_intron
ENST00000533733retained_intron
ENST00000533979protein_coding_CDS_not_defined
ENST00000601453protein_coding
ENST00000638443nonsense_mediated_decay
ENST00000638786protein_coding_CDS_not_defined
ENST00000639240protein_coding
ENST00000639953protein_coding
ENST00000640388protein_coding
ENST00000675595nonsense_mediated_decay
ENST00000675843protein_coding
ENST00000682147protein_coding_CDS_not_defined
ENST00000682286protein_coding_CDS_not_defined
ENST00000682289retained_intron
ENST00000682302retained_intron
ENST00000682430protein_coding_CDS_not_defined
ENST00000682465protein_coding
ENST00000682516protein_coding_CDS_not_defined
ENST00000682569retained_intron
ENST00000682956retained_intron
ENST00000683100retained_intron
ENST00000683150protein_coding
ENST00000683174nonsense_mediated_decay
ENST00000683468protein_coding
ENST00000683488retained_intron
ENST00000683524protein_coding_CDS_not_defined
ENST00000683605retained_intron
ENST00000683914protein_coding
ENST00000684029protein_coding
ENST00000684037nonsense_mediated_decay
ENST00000684061retained_intron
ENST00000684152retained_intron
ENST00000684179retained_intron
ENST00000684180retained_intron
ENST00000684447retained_intron
ENST00000713593nonsense_mediated_decay
ENST00000713840nonsense_mediated_decay
ENST00000713841nonsense_mediated_decay
ENST00000713842nonsense_mediated_decay
ENST00000713843nonsense_mediated_decay
ENST00000713844protein_coding
ENST00000713845protein_coding
ENST00000713846protein_coding
ENST00000713847protein_coding
ENST00000923922protein_coding
ENST00000971291protein_coding

RefSeq mRNA Transcripts (NM_)

Total: 12 NM_ accessions

RefSeq IDStatusMANE Select
NM_000051REVIEWED✓
NM_001106821PROVISIONAL
NM_001178328REVIEWED
NM_001339354REVIEWED
NM_001339355REVIEWED
NM_001339356REVIEWED
NM_001351834REVIEWED
NM_001351835REVIEWED
NM_001351836REVIEWED
NM_007499VALIDATED
NM_113518REVIEWED
NM_128315REVIEWED

CCDS Identifiers

  • CCDS31669
  • CCDS86245

MANE Select / Canonical Transcript Exons

Transcript: ENST00000675843 (NM_000051)
Total exons: 63

Exon IDStartEndStrandChromosome
ENSE00003129472108235670108235834+11
ENSE00003725082108227776108227888+11
ENSE00003742933108227595108227696+11
ENSE00003744805108229178108229323+11
ENSE00004021445108316011108316113+11
ENSE00004021446108315823108315911+11
ENSE00004021447108365082108365218+11
ENSE00004021448108329021108329238+11
ENSE00004021449108256215108256340+11
ENSE00004021450108284227108284473+11
ENSE00004021451108294927108295059+11
ENSE00004021452108310160108310315+11
ENSE00004021453108365325108369102+11
ENSE00004021454108244788108245026+11
ENSE00004021455108343222108343371+11
ENSE00004021456108331879108332037+11
ENSE00004021457108246964108247127+11
ENSE00004021458108332762108332900+11
ENSE00004021459108307897108307984+11
ENSE00004021460108319954108320058+11
ENSE00004021461108335845108335961+11
ENSE00004021462108271064108271146+11
ENSE00004021463108279491108279608+11
ENSE00004021464108289602108289801+11
ENSE00004021465108325310108325544+11
ENSE00004021466108272532108272607+11
ENSE00004021467108280995108281168+11
ENSE00004021468108330214108330421+11
ENSE00004021469108243953108244118+11
ENSE00004021470108333886108333968+11
ENSE00004021471108347279108347365+11
ENSE00004021472108282710108282879+11
ENSE00004021473108248933108249102+11
ENSE00004021474108223067108223186+11
ENSE00004021475108252817108252912+11
ENSE00004021476108327645108327758+11
ENSE00004021477108293313108293477+11
ENSE00004021478108253814108254039+11
ENSE00004021479108297287108297382+11
ENSE00004021480108299714108299885+11
ENSE00004021481108345743108345908+11
ENSE00004021482108287600108287715+11
ENSE00004021483108258986108259075+11
ENSE00004021484108257481108257606+11
ENSE00004021485108302853108303029+11
ENSE00004021486108317373108317521+11
ENSE00004021487108321301108321420+11
ENSE00004021488108271251108271406+11
ENSE00004021489108292619108292793+11
ENSE00004021490108288977108289103+11
ENSE00004021491108326058108326225+11
ENSE00004021492108331444108331557+11
ENSE00004021493108250701108251072+11
ENSE00004021494108267171108267342+11
ENSE00004021495108301648108301789+11
ENSE00004021496108304675108304852+11
ENSE00004021497108251837108252031+11
ENSE00004021498108268410108268609+11
ENSE00004021499108353766108353880+11
ENSE00004021500108272722108272852+11
ENSE00004021501108334969108335109+11
ENSE00004021502108354811108354874+11
ENSE00004021503108312411108312498+11

Protein identifiers

UniProt Accessions

  • Q13315 (canonical, reviewed) — Serine-protein kinase ATM | Ataxia telangiectasia mutated

RefSeq Proteins (NP_)

AccessionStatusGeneMANE Select
NP_000042REVIEWEDATM✓ Canonical
NP_001100291PROVISIONALAtm
NP_001319707REVIEWEDATM
NP_001326745REVIEWEDATM
NP_001326746REVIEWEDATM
NP_001338763REVIEWEDATM
NP_001338764REVIEWEDATM
NP_001338765REVIEWEDATM
NP_009465REVIEWEDTEL1
NP_031525VALIDATEDAtm
NP_180324REVIEWEDATC
NP_189242REVIEWEDTEL1

Protein Domains and Families

InterPro (IPR)

IDNameType
IPR000403Phosphatidylinositol 3-/4-kinase, catalytic domainDomain
IPR003151PIK-related kinase, FATDomain
IPR003152FATC domainDomain
IPR011009Protein kinase-like domain superfamilyHomologous superfamily
IPR014009PIK-related kinase, FAT domainDomain
IPR016024Armadillo-type foldHomologous superfamily
IPR018936Phosphatidylinositol 3-/4-kinase, conserved siteConserved site
IPR021668Telomere-length maintenance and DNA damage repair (TAN)Domain
IPR036940Phosphatidylinositol 3-/4-kinase, catalytic domain superfamilyHomologous superfamily
IPR038980Serine/threonine-protein kinase ATM, plantFamily
IPR044107ATM, catalytic domain (PIKKc_ATM)Domain

Pfam (PF)

  • PF00454
  • PF02259
  • PF02260
  • PF11640

SMART (SM)

  • SM00146
  • SM01342
  • SM01343

Superfamily (SSF)

  • SSF48371
  • SSF56112

Antibody Availability

No antibody resources found in biobtree for ATM protein.

Structure

Experimental Structures: 14 PDB Entries

PDB IDTitleMethodResolution
5NP0Closed dimer of human ATMCryo-EM5.7 Å
5NP1Open protomer of human ATMCryo-EM5.7 Å
6HKAFATC domain of human ATMNMRNot reported
6K9KMonomeric human ATM kinaseCryo-EM7.82 Å
6K9LDimeric ATM kinaseCryo-EM4.27 Å
7NI4ATM kinase with M4076 inhibitorCryo-EM3.0 Å
7NI5ATM kinase with KU-55933 inhibitorCryo-EM2.78 Å
7NI6ATM kinase with ATPySCryo-EM2.8 Å
7SICHuman ATM DimerCryo-EM2.51 Å
7SIDHuman ATM Dimer bound to Nbs1Cryo-EM2.53 Å
8OXMATM(Q2971A) with AMP-PNP and p53 peptideCryo-EM3.3 Å
8OXOATM(Q2971A) C-terminal dimer with AMP-PNP and p53 peptideCryo-EM3.0 Å
8OXPATM(Q2971A) with AMP-PNPCryo-EM2.6 Å
8OXQATM(Q2971A) C-terminal dimer with AMP-PNPCryo-EM2.5 Å

Total: 14 experimental structures (13 Cryo-EM, 1 NMR)

Predicted Structures

AlphaFold Model: AF-Q13315-F1 (v2) or AF-Q13315-F4 (v3/v4)
pLDDT Confidence Metrics: Data not available in queried biobtree dataset

Cross-species orthologs

OrganismGene IDSymbol
Mouse (Mus musculus)ENSMUSG00000034218Atm
Rat (Rattus norvegicus)ENSRNOG00000029773Atm
Zebrafish (Danio rerio)ENSDARG00000002385atm
Fruit fly (Drosophila melanogaster)FBGN0045035tefu
Worm (C. elegans)WBGENE00000467cep-1
Yeast (S. cerevisiae)852190TEL1

Clinical variants & AI predictions

ClinVar Variant Classification

ClassificationEstimated Count
Pathogenic~3,000+
Likely Pathogenic~1,500+
Uncertain Significance~12,000+
Likely Benign~600+
Benign~100+
Total~18,200

Top 30 Pathogenic/Likely Pathogenic Variants

ClinVar IDHGVS NotationCondition/Classification
141167c.283C>T (p.Gln95Ter)Pathogenic - Nonsense
141373c.8998C>T (p.Gln3000Ter)Pathogenic - Nonsense
141240c.8505C>A (p.Cys2835Ter)Pathogenic - Nonsense
141233c.7913G>A (p.Trp2638Ter)Pathogenic - Nonsense
141846c.4227del (p.Ser1411fs)Pathogenic - Frameshift
141734c.3381_3384del (p.Gln1128fs)Pathogenic - Frameshift
141546c.381del (p.Thr127_Val128insTer)Pathogenic - Frameshift
1071816c.856C>T (p.Gln286Ter)Pathogenic - Nonsense
1069441c.1262C>G (p.Ser421Ter)Pathogenic - Nonsense
1069197c.1179G>A (p.Trp393Ter)Pathogenic - Nonsense
127417c.6100C>T (p.Arg2034Ter)Pathogenic - Nonsense
142057c.2921+1G>TPathogenic - Splice site
1066028c.2638+1G>TPathogenic/Likely Pathogenic - Splice site
141218c.6095+1G>APathogenic - Splice site
127426c.6572+1G>APathogenic/Likely Pathogenic - Splice site
1068261c.7788+1G>APathogenic/Likely Pathogenic - Splice site
1066285c.8151+1G>APathogenic/Likely Pathogenic - Splice site
1066672c.7307+1G>APathogenic/Likely Pathogenic - Splice site
1068029c.4436+1G>APathogenic/Likely Pathogenic - Splice site
127470c.9112del (p.Gln3038fs)Pathogenic - Frameshift
127445c.7456C>T (p.Arg2486Ter)Pathogenic - Nonsense
127432c.6976-10_6989delPathogenic - Deletion
140823c.6047A>G (p.Asp2016Gly)Pathogenic/Likely Pathogenic - Missense
142700c.8147T>C (p.Val2716Ala)Pathogenic - Missense
142791c.8122G>A (p.Asp2708Asn)Pathogenic - Missense
141522c.3284G>A (p.Arg1095Lys)Likely Pathogenic - Missense
142187c.9022C>T (p.Arg3008Cys)Likely Pathogenic - Missense
1013733c.3248A>G (p.His1083Arg)Pathogenic/Likely Pathogenic - Missense
127362c.2932T>C (p.Ser978Pro)Benign - Note: contradictory annotation
1068803c.3455_3456del (p.Ser1152fs)Pathogenic/Likely Pathogenic - Frameshift

SpliceAI Splice Effect Predictions

Total Count: ~11,573 predictions

Variant PositionGeneEffect TypeScore
11:108223865:C:GATMdonor_gain0.99
11:108223864:GC:GATMdonor_gain0.98
11:108223065:G:GGATMdonor_gain0.98
11:108223062:G:GTATMdonor_gain0.97
11:108223056:G:GTATMdonor_gain0.97
11:108223062:GGA:GATMdonor_gain0.97
11:108223019:G:GTATMdonor_gain0.99
11:108223019:GAA:GATMdonor_gain0.97
11:108223022:G:GGATMdonor_gain0.97
11:108223021:A:AGATMdonor_gain0.95
11:108223063:GAG:GATMdonor_gain0.97
11:108223063:GA:GATMdonor_gain0.95
11:108223033:G:GTATMdonor_gain0.80
11:108222959:A:AGATMdonor_gain0.97
11:108222965:G:GTATMdonor_gain0.96
11:108222931:G:GTATMdonor_gain0.88
11:108222931:G:TATMdonor_gain0.87
11:108222899:C:TATMdonor_gain0.79
11:108222885:G:GAATMdonor_gain0.84
11:108222884:T:TAATMdonor_gain0.73
11:108222852:C:TATMdonor_gain0.79
11:108223061:GGGA:GATMdonor_gain0.96
11:108222966:A:GATMdonor_gain0.77
11:108223033:G:TATMdonor_gain0.72
11:108223025:G:AATMdonor_gain0.73
11:108222975:GGCA:GATMdonor_gain0.67
11:108222850:G:GTATMdonor_gain0.67
11:108223050:G:GTATMdonor_gain0.63
11:108223048:T:AATMdonor_gain0.68
11:108223051:A:TATMdonor_gain0.52

AlphaMissense Likely Pathogenic Predictions

Total Count: ~3,000+ likely_pathogenic predictions

Variant PositionGeneProtein ChangePathogenicity Score
11:108227872:T:GATMW57G0.965
11:108227872:T:AATMW57R0.998
11:108227872:T:CATMW57R0.998
11:108227874:G:CATMW57C0.996
11:108227874:G:TATMW57C0.996
11:108227873:G:CATMW57S0.987
11:108227831:T:CATML43P0.994
11:108227647:T:CATML8P0.992
11:108227692:G:CATMR23P0.992
11:108227796:G:CATMK31N0.903
11:108227796:G:TATMK31N0.903
11:108227668:T:CATML15P0.978
11:108227801:T:CATML33P0.978
11:108227831:T:AATML43Q0.980
11:108227659:G:AATMC12Y0.926
11:108227659:G:CATMC12S0.795
11:108227658:T:CATMC12R0.972
11:108227650:T:CATML9P0.923
11:108227647:T:AATML8Q0.969
11:108227647:T:GATML8R0.963
11:108227804:T:GATMI34S0.902
11:108227833:G:CATMD44H0.968
11:108227834:A:TATMD44V0.949
11:108227668:T:GATML15R0.946
11:108227630:T:AATMS2R0.929
11:108227630:T:GATMS2R0.929
11:108227628:A:CATMS2R0.929
11:108227804:T:AATMI34N0.931
11:108227831:T:GATML43R0.966
11:108227873:G:TATMW57L0.967

Pathways & Gene Ontology

Reactome Pathways

Total: 28 pathways (23 canonical + 5 disease-related)

Pathway IDPathway Name
R-HSA-2559586DNA Damage/Telomere Stress Induced Senescence
R-HSA-3371453Regulation of HSF1-mediated heat shock response
R-HSA-349425Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-5685938HDR through Single Strand Annealing (SSA)
R-HSA-5685942HDR through Homologous Recombination (HRR)
R-HSA-5693548Sensing of DNA Double Strand Breaks
R-HSA-5693554Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571Nonhomologous End-Joining (NHEJ)
R-HSA-5693579Homologous DNA Pairing and Strand Exchange
R-HSA-5693607Processing of DNA double-strand break ends
R-HSA-5693616Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6796648TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6803204TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-6803207TP53 Regulates Transcription of Caspase Activators and Caspases
R-HSA-6804756Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757Regulation of TP53 Degradation
R-HSA-6804760Regulation of TP53 Activity through Methylation
R-HSA-69473G2/M DNA damage checkpoint
R-HSA-69541Stabilization of p53
R-HSA-912446Meiotic recombination
R-HSA-9664873Pexophagy
R-HSA-9701192Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331Defective HDR through HRR due to PALB2 loss of BRCA1 binding function
R-HSA-9704646Defective HDR through HRR due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709570Impaired BRCA2 binding to RAD51
R-HSA-9709603Impaired BRCA2 binding to PALB2

MSigDB Gene Sets

Total: 100 gene sets (KEGG pathways, GO gene sets, canonical pathways, transcription factor targets, miRNA targets)

Gene Ontology Annotations

Biological Process: 68 terms (TOP 20)

GO IDTerm
GO:0000077DNA damage checkpoint signaling
GO:0000425pexophagy
GO:0000723telomere maintenance
GO:0000724double-strand break repair via homologous recombination
GO:0000729DNA double-strand break processing
GO:0001541ovarian follicle development
GO:0001756somitogenesis
GO:0002331pre-B cell allelic exclusion
GO:0006302double-strand break repair
GO:0006303double-strand break repair via nonhomologous end joining
GO:0006468protein phosphorylation
GO:0006974DNA damage response
GO:0007094mitotic spindle assembly checkpoint signaling
GO:0007095mitotic G2 DNA damage checkpoint signaling
GO:0007131reciprocal meiotic recombination
GO:0007140male meiotic nuclear division
GO:0007143female meiotic nuclear division
GO:0007165signal transduction
GO:0007420brain development
GO:0007507heart development

Molecular Function: 9 terms (all)

GO IDTerm
GO:0003677DNA binding
GO:0004674protein serine/threonine kinase activity
GO:0004677DNA-dependent protein kinase activity
GO:0005524ATP binding
GO:00163031-phosphatidylinositol-3-kinase activity
GO:0035979histone H2AXS139 kinase activity
GO:0042802identical protein binding
GO:0044877protein-containing complex binding
GO:0106310protein serine kinase activity

Cellular Component: 12 terms (all)

GO IDTerm
GO:0005634nucleus
GO:0005654nucleoplasm
GO:0005694chromosome
GO:0005730nucleolus
GO:0005737cytoplasm
GO:0005782peroxisomal matrix
GO:0005813centrosome
GO:0005819spindle
GO:0005829cytosol
GO:0035861site of double-strand break
GO:0098850extrinsic component of synaptic vesicle membrane
GO:1990391DNA repair complex

Protein interactions & networks

Protein-protein interactions (PPIs)

Total interactions: ~6,600 interaction records across major databases:

  • STRING: 6,446 records (highest-confidence curated interactions)
  • BioGRID: 668 experimentally validated interactions
  • IntAct: 264 direct/physical interactions with confidence scores

TOP 30 highest-confidence interacting proteins (STRING score 999–835):

UniProtGeneProtein NameSTRING Score
O96017CHEK2Serine/threonine-protein kinase Chk2999
P38398BRCA1Breast cancer type 1 susceptibility protein999
Q14676MDC1Mediator of DNA damage checkpoint protein 1997
Q12888TP53BP1TP53-binding protein 1996
P43246MSH2DNA mismatch repair protein Msh2995
Q8WXE1ATRIPATR-interacting protein995
P52701MSH6DNA mismatch repair protein Msh6994
P40692MLH1DNA mismatch repair protein Mlh1992
P16104H2AFXHistone H2AX984
O14757CHEK1Serine/threonine-protein kinase Chk1975
P04637TP53Cellular tumor antigen p53975
P51587BRCA2Breast cancer type 2 susceptibility protein972
Q9BXW9FANCD2Fanconi anemia group D2 protein968
P13010XRCC5DNA repair protein Ku80964
O43313ATMINATM interactor961
Q06609RAD51DNA repair protein RAD51 homolog 1958
Q8N2W9PIAS4E3 SUMO-protein ligase PIAS4956
Q00987MDM2E3 ubiquitin-protein ligase Mdm2955
Q9Y6K9IKBKGNF-kappa-B essential modulator949
P49959MRE11Double-strand break repair protein MRE11941
O60934NBNNibrin (DNA repair complex)936
Q92993KAT5Histone acetyltransferase KAT5936
P12956XRCC6DNA repair protein Ku70931
O15297PPM1DProtein phosphatase 1D924
Q13547HDAC1Histone deacetylase 1923
O75943RAD17Cell cycle checkpoint protein RAD17912
Q09472EP300Histone acetyltransferase p300901
Q6ZW49PAXIP1PAX-interacting protein 1900
P60484PTENPhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase PTEN893
Q99728BARD1BRCA1-associated RING domain protein 1893

Key functional clusters: DNA damage response (CHEK1/2, TP53, H2AFX), DNA repair (BRCA1/2, MSH2/6, MLH1, RAD51, MRE11), checkpoint control (MDC1, TP53BP1), chromatin remodeling (HDAC1, KAT5, EP300).

Protein similarity

Structural/Embedding Similarity (ESM2 embeddings; 88 homologs identified)

UniProtTop SimilarityAvg SimilarityDescription
Q17QT71.00000.9891ATM ortholog (extremely similar structure)
Q2KJI31.00000.9894ATM ortholog
Q8BHZ01.00000.9890ATM ortholog
Q9NUQ91.00000.9894ATM ortholog
Q96Q150.99990.9925ATM-related kinase (97.7% identity)
Q95JJ50.99990.9907ATM ortholog
Q8TEL60.99990.9903ATM-related
O431490.99960.9896Zinc finger domain protein
Q5R4M20.99970.9887ATM-related kinase
Q8K2A70.99970.9916ATM-related
Q5ZLS80.99970.9916ATM-related kinase
Q5ZM410.99910.9908ATM-related
Q6DFV10.99950.9922ATM-related kinase
Q5SSH70.99960.9895ATM-related
Q5VW360.99930.9924ATM-related kinase
Q5UIP00.99960.9895ATM-related
Q96M890.99990.9907ATM ortholog
P785270.99940.9936DNA-dependent protein kinase catalytic subunit
Q5XI940.99920.9910ATM-related kinase
Q6PR540.99960.9894ATM-related

Sequence Homology (DIAMOND BLAST; 30 homologs identified)

UniProtIdentity %BitscoreGene/Description
Q8BKX697.706,960ATM ortholog (very high conservation)
Q96Q1597.706,960ATM-related kinase
Q9Z1L098.402,109ATM-related protein
Q8BTI998.402,107Checkpoint/ATM-like kinase
C5J7W873.405,246ATM ortholog
Q1331588.405,370ATM (self)
Q6PQD588.405,360ATM-like kinase
Q1353590.304,737ATR (ATM and Rad3-related)
Q6238883.805,063ATM ortholog
Q5BHE262.003,474ATM-like protein
P3260068.503,249Serine/threonine kinase
P3516968.303,269Serine/threonine kinase
Q6FX4254.102,543Kinase-related protein
Q75DB856.302,194Checkpoint kinase-like
O1435652.102,329DNA damage kinase
Q9Y7K252.002,318Serine/threonine kinase
Q6CT3450.602,163Kinase domain protein
Q95Q9543.501,390Protein kinase
Q6CAD242.30442Kinase-related
Q9N3Q441.00229Distantly related kinase

Summary: ATM shares highest structural similarity with orthologs across species (>0.99 ESM2 similarity) and sequence homology with ATR (90.3% identity, related apical kinase). Most similar proteins cluster in the PIKK (phosphoinositide 3-kinase-related kinase) superfamily and checkpoint control pathways.

Transcription factor regulatory data

Note: ATM (Ataxia Telangiectasia Mutated) is a serine/threonine kinase, not a sequence-specific DNA binding transcription factor. JASPAR motifs are not available for ATM. However, ATM has documented regulatory interactions affecting gene expression, primarily through kinase-mediated signaling that modulates transcription factor activity.

Downstream targets: 27 total

TOP 27 genes regulated by ATM (from CollecTRI/TRRUST and other curated sources):

TargetRegulationEvidence
GADD45AActivatesTRRUST
BAXActivatesTRRUST
CFLARActivatesTRRUST
FASActivatesTRRUST
DUSP1ActivatesTRRUST
FOXM1ActivatesTRRUST
MCL1ActivatesTRRUST
E2F1ActivatesGOA
PMAIP1RepressesTRRUST
BCL2RepressesTRRUST
VEGFARepressesTRRUST
TERF1RepressesTRRUST
TNFRSF10BRepressesTRRUST
CDKN1AUnknownTRRUST
PCNAUnknownTRRUST
PBKUnknownTRRUST
APLFUnknownTRRUST
COL3A1UnknownTRRUST
ZFHX3UnknownTRRUST
SLC2A1UnknownTRRUST
PVRUnknownTRRUST
PDGFRBUnknownTRRUST
MTF1UnknownTRRUST
KLRK1UnknownTRRUST
ITGA8UnknownTRRUST
IGF1RUnknownTRRUST
SP1UnknownTRRUST

Upstream regulators: 26 total

Transcription factors that regulate ATM:

RegulatorRegulationEvidence TypeConfidence
E2F1ActivatesExTRI, TRRUST, TFactS, SIGNOR, GEREDB, Pavlidis2021, DoRothEA_AHigh
BRCA1ActivatesTRRUST, SIGNORExperimentally validated
MYCActivatesGEREDBPredicted
TP63UnknownExTRIHigh
FOXO3UnknownExTRI, GEREDB, NTNU CuratedHigh
E2F3UnknownPredicted-
SP1UnknownExTRI, TRRUST, DoRothEA_ALow
RELAUnknownExTRILow
AHRUnknownExTRILow
DMAP1UnknownTRRUST-
ARUnknownDoRothEA_A-
BTF3UnknownPredicted-
NFATC2UnknownPredicted-
TWIST1UnknownPredicted-
MEF2DUnknownPredicted-
GLI3UnknownPredicted-
RBPJUnknownPredicted-
TFCP2UnknownPredicted-
GRHL3UnknownPredicted-
RBBP8UnknownPredicted-
KMT2AUnknownPredicted-
TWIST2UnknownPredicted-
NR2C2UnknownPredicted-
NFAT5UnknownPredicted-
ZNF148UnknownPredicted-
AP1UnknownPredicted-

Evidence sources: TRRUST (manually curated), ExTRI (experimentally validated), SIGNOR (signaling network), GEREDB (gene regulation database), NTNU Curated (expert curation), DoRothEA_A (inference from regulatory networks)

Drug & pharmacology data

ATM is an established drug target with 100+ molecules in ChEMBL targeting the serine/threonine kinase domain (CHEMBL3797).

Targeting molecules

  • Total count: 100+ compounds in ChEMBL

  • High-phase molecules (Phase 1-2):

    1. BERZOSERTIB (CHEMBL3989870) — Phase 2, ATR kinase inhibitor (also blocks ATM), 23 clinical trials
    2. NEDISERTIB/peposertib (CHEMBL4297629, M3814) — Phase 1, DNA-PK inhibitor with ATM activity, 18 clinical trials
    3. AZD-0156 (CHEMBL4297899) — Phase 1, ATM kinase inhibitor, 1 clinical trial
    4. STREPTONIGRIN (CHEMBL11417) — Phase 2, topoisomerase inhibitor
    5. CALCIMYCIN (CHEMBL1256686) — Phase 2, calcium ionophore

  • Phase 4 (Approved, off-target activity):

    • AMIODARONE HYDROCHLORIDE (CHEMBL1083993) — antiarrhythmic
    • AMITRIPTYLINE HYDROCHLORIDE (CHEMBL1200964) — tricyclic antidepressant
    • NAFTIFINE HYDROCHLORIDE (CHEMBL1200493) — antifungal
    • ESTRADIOL ACETATE (CHEMBL1200430) — hormone
    • METHYSERGIDE MALEATE (CHEMBL1200938) — antimigraine agent

Clinical trials (top 20)

Predominantly early-phase trials (Phase 1-2) combining ATM/ATR inhibitors with chemotherapy or radiation:

Berzosertib (23 trials):

  • NCT02487095 — Topotecan + VX-970 in small cell cancers (COMPLETED, Ph1/2)
  • NCT02567409 — Cisplatin + gemcitabine ± berzosertib in urothelial cancer (COMPLETED, Ph2)
  • NCT02595892 — Gemcitabine ± M6620 in ovarian cancer (ACTIVE_NOT_RECRUITING, Ph2)
  • NCT03517969 — M6620 + carboplatin ± docetaxel in CRPC (ACTIVE_NOT_RECRUITING, Ph2)
  • NCT04216316 — Berzosertib + carboplatin/gemcitabine/pembrolizumab in NSCLC (ACTIVE_NOT_RECRUITING, Ph1/2)
  • NCT04802174 — Lurbinectedin + berzosertib in SCLC (RECRUITING, Ph1/2)
  • NCT04826341 — Sacituzumab govitecan + berzosertib in SCLC/HR-deficient cancers (RECRUITING, Ph1/2)

Nedisertib/Peposertib (18 trials):

  • NCT04071236 — Radium-223 ± M3814 ± avelumab in advanced prostate cancer (RECRUITING, Ph1/2)
  • NCT04172532 — M3814 + radiotherapy in pancreatic cancer (RECRUITING, Ph1/2)
  • NCT03770689 — Peposertib + capecitabine + RT in rectal cancer (COMPLETED, Ph1/2)
  • NCT04555577 — Peposertib + radiation + temozolomide in glioblastoma (RECRUITING, Ph1)
  • NCT05711615 — Low-dose doxorubicin + peposertib in advanced sarcoma (RECRUITING, Ph1)

AZD-0156 (1 trial):

  • NCT02588105 — AZD0156 alone or with other agents in advanced cancer (COMPLETED, Ph1)

Pharmacogenomics

  • PharmGKB status: ATM (PA61) is flagged as a VIP (Very Important Pharmacogene) with documented variant annotations
  • Known interactions: ATM variants associated with ataxia-telangiectasia and cancer predisposition; limited formal pharmacogenomic guidelines for ATM inhibitor dosing
  • Clinical relevance: ATM deficiency/mutation status considered for patient selection in DDR-deficient tumor trials; no standard pharmacogenomic-guided dosing protocols published

Based on the biobtree data available for the human ATM gene (ENSG00000149311), here’s the expression summary:

Expression profiles

Tissue Expression (Bgee)

ATM shows ubiquitous expression across human tissues with gold-quality expression data from 277 conditions. The gene has a maximum expression score of 97.33 and an average score of 85.83, indicating broad and generally high expression across tissues.

RankTissue/Anatomical StructureExpression StatusScore
1Calcaneal tendonPresent97.33
2Colonic epitheliumPresent97.24
3Corpus callosumPresent96.41
4Lymph nodePresent96.36
5Bone marrow cellPresent96.26
6Body of pancreasPresent95.70
7Adrenal tissuePresent95.39
8Sural nervePresent95.28
9TonsilPresent95.10
10TendonPresent94.86
11Superficial temporal arteryPresent94.55
12Ventricular zonePresent94.50
13Buccal mucosa cellPresent94.38
14LeukocytePresent94.37
15SpleenPresent94.31
16Mononuclear cellPresent94.26
17MonocytePresent94.26
18GranulocytePresent94.24
19Left ovaryPresent93.84
20Male germ line stem cell in testisPresent93.75
21Right ovaryPresent93.70
22Pituitary glandPresent93.10
23C1 segment of cervical spinal cordPresent93.01
24Epithelium of nasopharynxPresent92.81
25NasopharynxPresent92.79
26Trigeminal ganglionPresent92.74
27Ganglionic eminencePresent92.73
28Bone marrowPresent92.60
29BloodPresent92.52
30Vermiform appendixPresent92.50

Tissue-specific patterns: ATM is highly expressed in lymphoid tissues (lymph node, spleen, tonsil, bone marrow), immune cell types (leukocytes, monocytes, granulocytes), reproductive tissues (ovaries, testis), and connective tissues (tendons, nerves). This pattern aligns with ATM’s role in DNA damage response and cell cycle checkpoint control, critical for rapidly dividing immune and germ cells.

Single-Cell Expression (SCXA)

ATM is profiled across 12 single-cell RNA-seq experiments from Single Cell Expression Atlas, spanning 610 cell clusters with maximum mean expression of 1811.22 and average expression of 385.95.

Notable SCXA datasets:

  • E-CURD-97: CD4+ regulatory T cells and memory T cells from multiple tissues (1,677 cells)
  • E-HCAD-31: Pancreatic islet cells, healthy and type II diabetic (38,217 cells)
  • E-MTAB-11011: B cells in COVID-19, active and recovered disease (15,100 cells)
  • E-MTAB-8911: Clonally expanded T-lymphocytes in chronic graft-versus-host disease (19,075 cells)
  • E-MTAB-9067: Fetal liver and bone marrow hematopoiesis (5,865 cells)
  • E-MTAB-9221: Whole blood from COVID-19 patients and controls (27,943 cells)
  • E-MTAB-6386: PBMC-derived B cells from healthy donors (117 cells)
  • E-MTAB-7303: iPSC-derived dopamine neurons for Parkinson’s disease modeling (123 cells)

Single-cell patterns: ATM expression is particularly prominent in hematopoietic and immune cell lineages (T cells, B cells, monocytes), consistent with the gene’s role in immunological function and the disease phenotype of ataxia-telangiectasia (immune deficiency).

Disease associations

Mendelian / Monogenic Diseases

Primary Condition:

DiseaseID(s)InheritanceEvidence Level
Ataxia telangiectasiaOMIM:208900, MONDO:0008840, Orphanet:100Autosomal recessiveDefinitive/Strong

Cancer Predisposition Syndromes:

DiseaseID(s)InheritanceEvidence Level
Hereditary breast carcinomaOMIM:114480, MONDO:0016419Autosomal dominantDefinitive
ATM-related cancer predispositionMONDO:0700270Autosomal dominantDefinitive
Ataxia-telangiectasia variantMONDO:0018266, Orphanet:370109Autosomal recessiveModerate
Prostate cancer (familial)MONDO:0700275, MONDO:0008315Autosomal dominantModerate
Gastric carcinomaMONDO:0001056, MONDO:0004950Autosomal dominantLimited
Hereditary nonpolyposis colon cancerMONDO:0018630Autosomal dominantLimited
SarcomaMONDO:0005089Autosomal dominantModerate

Phenotype Associations (HPO Terms)

Top 30 Clinical Phenotypes:

  1. HP:0001251 - Ataxia
  2. HP:0000524 - Conjunctival telangiectasia
  3. HP:0000639 - Nystagmus
  4. HP:0001288 - Gait disturbance
  5. HP:0100579 - Mucosal telangiectasiae
  6. HP:0100585 - Telangiectasia of the skin
  7. HP:0002715 - Abnormality of the immune system
  8. HP:0002721 - Immunodeficiency
  9. HP:0005374 - Cellular immunodeficiency
  10. HP:0004315 - Decreased circulating IgG concentration
  11. HP:0002720 - Decreased circulating IgA concentration
  12. HP:0001888 - Decreased total lymphocyte count
  13. HP:0005403 - Decreased total T cell count
  14. HP:0000252 - Microcephaly
  15. HP:0004322 - Short stature
  16. HP:0003220 - Abnormality of chromosome stability
  17. HP:0002664 - Neoplasm
  18. HP:0003002 - Breast carcinoma
  19. HP:0001402 - Hepatocellular carcinoma
  20. HP:0002861 - Melanoma
  21. HP:0001909 - Leukemia
  22. HP:0006721 - Acute lymphoblastic leukemia
  23. HP:0002665 - Lymphoma
  24. HP:0012539 - Non-Hodgkin lymphoma
  25. HP:0012189 - Hodgkin lymphoma
  26. HP:0002073 - Progressive cerebellar ataxia
  27. HP:0001250 - Seizure
  28. HP:0100543 - Cognitive impairment
  29. HP:0001508 - Failure to thrive
  30. HP:0007495 - Prematurely aged appearance

Complex Disease / GWAS Associations

Top 30 Genome-Wide Association Studies:

Trait/DiseaseP-valueMapped GeneStudy
Eosinophil count3.0e-29ATMGCST90002381
Eosinophil percentage of white cells8.0e-21ATMGCST90002382
Cutaneous malignant melanoma2.0e-21ATMGCST010304
Nevus count or cutaneous melanoma4.0e-21ATMGCST010303
Refractive error4.0e-19C11orf65GCST010002
Red blood cell count1.0e-11ATMGCST005996
Uterine fibroids3.0e-12ATMGCST006462
Leukocyte telomere length7.0e-12C11orf65GCST008366
Myeloproliferative neoplasms2.0e-10ATMGCST90000032
Lymphocyte count6.0e-10C11orf65, ATMGCST90002388
Eosinophil count6.0e-09ATMGCST004600
Melanoma3.0e-09ATMGCST001267, GCST004142
Renal cell carcinoma9.0e-09ATMGCST004710
Prostate cancer8.0e-09ATMGCST006085
Response to metformin in type 2 diabetes3.0e-09C11orf65GCST000927
Mean reticulocyte volume3.0e-09ATMGCST90002396
Leukocyte telomere length2.0e-10C11orf65GCST008366
Uterine fibroids7.0e-08ATMGCST006462
Gastric cancer6.0e-07ATMGCST002992
Rheumatoid arthritis1.0e-08ATMGCST002318
Gastric adenocarcinoma (histologically verified)2.0e-07ATMGCST002990
Rheumatoid arthritis4.0e-07CUL5GCST006959
Alzheimer’s disease (late onset)6.0e-07C11orf65, ATMGCST005549
Nevus count or cutaneous melanoma8.0e-11C11orf65, ATMGCST007505
Nonunion in individuals with fractures3.0e-07—GCST007250
Uterine fibroids3.0e-11ATMGCST006462
Gastric adenocarcinoma1.0e-06ATMGCST002990
Gastric cancer3.0e-06ATMGCST002992
Leukocyte telomere length1.0e-08ATMGCST009856
Rheumatoid arthritis1.0e-08ATMGCST002318

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 42 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, ensembl, entrez, esm2_similarity, exon, gencc, go, gwas, hgnc, hpa, hpo, intact, interpro, jaspar, mim, mondo, msigdb, orphanet, pdb, pfam, pharmgkb_gene, reactome, refseq, scxa, scxa_expression, smart, spliceai, string_interaction, supfam, transcript, uniprot
Generated: 2026-05-25 — For the latest data, query BioBTree directly via MCP or API.
View API calls (216)