BLM
BLM RecQ like helicase, the group of RecQ like helicases
Basic information
Region (hg38): 15:90717346-90816166
Links
Phenotypes
GenCC
Source:
- Bloom syndrome (Definitive), mode of inheritance: AR
- Bloom syndrome (Definitive), mode of inheritance: AR
- osteosarcoma (Moderate), mode of inheritance: AR
- Bloom syndrome (Moderate), mode of inheritance: AR
- Bloom syndrome (Strong), mode of inheritance: AR
- Bloom syndrome (Definitive), mode of inheritance: AR
- Bloom syndrome (Supportive), mode of inheritance: AR
- breast cancer (Disputed Evidence), mode of inheritance: AD
- Bloom syndrome (Definitive), mode of inheritance: AR
- hereditary nonpolyposis colon cancer (Disputed Evidence), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Bloom syndrome | AR | Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Oncologic | Surveillance and early diagnosis of malignancy could potentially be beneficial; Avoidance of ionizing radiation/DNA-damaging chemicals (as well as sun exposure) can reduce morbidity; Individuals may be susceptible to infections, and prompt treatment, as well as control of gastroesophageal reflux, which can be contributory, can be beneficial | Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Pulmonary | 5923432; 7386453; 7273457; 6705251; 3040954; 3808032; 3808031; 2721026; 1809225; 7585968; 8875252; 9062585; 9285778; 10464606; 11477604; 12242432; 15137905; 17407155; 18471088; 18974064; 20301572; 21815139; 22514588; 23028338; 23443610; 24118499; 35420546 |
| Variants may also be related to risk of malignancy in the general poulation |
ClinVar
This is a list of variants' phenotypes submitted to
- Bloom_syndrome (3814 variants)
- Hereditary_cancer-predisposing_syndrome (2809 variants)
- not_provided (456 variants)
- not_specified (163 variants)
- BLM-related_disorder (71 variants)
- Hereditary_breast_ovarian_cancer_syndrome (18 variants)
- Hereditary_cancer (12 variants)
- Ovarian_cancer (11 variants)
- Colorectal_cancer (9 variants)
- Olaparib_response (3 variants)
- Microcephaly (3 variants)
- See_cases (1 variants)
- Endometrial_carcinoma (1 variants)
- Familial_cancer_of_breast (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BLM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000057.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 25 | 1032 | 1067 | |||
| missense | 21 | 2393 | 178 | 2605 | ||
| nonsense | 101 | 42 | 150 | |||
| start loss | 2 | 1 | 3 | |||
| frameshift | 218 | 106 | 10 | 336 | ||
| splice donor/acceptor (+/-2bp) | 79 | 88 | ||||
| Total | 330 | 252 | 2442 | 1211 | 14 |
Highest pathogenic variant AF is 0.000158002
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BLM | protein_coding | protein_coding | ENST00000355112 | 21 | 98302 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.54e-15 | 0.999 | 125554 | 0 | 194 | 125748 | 0.000772 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.887 | 664 | 731 | 0.908 | 0.0000362 | 9393 |
| Missense in Polyphen | 207 | 243.13 | 0.8514 | 3141 | ||
| Synonymous | 1.14 | 248 | 272 | 0.912 | 0.0000148 | 2626 |
| Loss of Function | 3.14 | 34 | 60.3 | 0.564 | 0.00000292 | 827 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00133 | 0.00130 |
| Ashkenazi Jewish | 0.00418 | 0.00418 |
| East Asian | 0.000544 | 0.000544 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.000796 | 0.000783 |
| Middle Eastern | 0.000544 | 0.000544 |
| South Asian | 0.000462 | 0.000457 |
| Other | 0.000338 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:9388193, PubMed:24816114, PubMed:25901030). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction (PubMed:20639533, PubMed:24257077, PubMed:25901030). {ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:9388193}.;
- Disease
- DISEASE: Bloom syndrome (BLM) [MIM:210900]: An autosomal recessive disorder. It is characterized by proportionate pre- and postnatal growth deficiency, sun-sensitive telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability. {ECO:0000269|PubMed:10862105, ECO:0000269|PubMed:7585968, ECO:0000269|PubMed:9285778}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Fanconi anemia pathway - Homo sapiens (human);Homologous recombination - Homo sapiens (human);HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;Generic Transcription Pathway;SUMOylation of DNA damage response and repair proteins;Homology Directed Repair;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;SUMOylation;Fanconi anemia pathway;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Regulation of Telomerase;Processing of DNA double-strand break ends;ATM pathway;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR)
(Consensus)
Recessive Scores
- pRec
- 0.617
Intolerance Scores
- loftool
- 0.959
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 42.36
Haploinsufficiency Scores
- pHI
- 0.760
- hipred
- Y
- hipred_score
- 0.715
- ghis
- 0.560
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.660
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Blm
- Phenotype
- neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; immune system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype;
Gene ontology
- Biological process
- regulation of cyclin-dependent protein serine/threonine kinase activity;resolution of meiotic recombination intermediates;double-strand break repair via homologous recombination;DNA double-strand break processing;DNA synthesis involved in DNA repair;strand displacement;DNA strand renaturation;DNA replication;DNA repair;double-strand break repair via nonhomologous end joining;DNA recombination;cellular response to DNA damage stimulus;mitotic G2 DNA damage checkpoint;response to X-ray;meiotic DNA double-strand break processing involved in reciprocal meiotic recombination;replication fork processing;DNA duplex unwinding;negative regulation of apoptotic process;G-quadruplex DNA unwinding;double-strand break repair via synthesis-dependent strand annealing;positive regulation of transcription, DNA-templated;negative regulation of DNA recombination;negative regulation of mitotic recombination;alpha-beta T cell differentiation;positive regulation of alpha-beta T cell proliferation;replication fork protection;protein complex oligomerization;protein homooligomerization;meiotic chromosome separation;negative regulation of cell division;telomeric D-loop disassembly;negative regulation of thymocyte apoptotic process;resolution of recombination intermediates;cellular response to ionizing radiation;cellular response to hydroxyurea;cellular response to camptothecin;regulation of DNA-dependent DNA replication;t-circle formation;negative regulation of double-strand break repair via single-strand annealing;positive regulation of double-strand break repair via homologous recombination
- Cellular component
- nuclear chromosome;chromosome, telomeric region;lateral element;nucleus;nucleoplasm;replication fork;chromosome;nucleolus;cytoplasm;cytosol;nuclear matrix;PML body;pronucleus
- Molecular function
- four-way junction DNA binding;Y-form DNA binding;bubble DNA binding;p53 binding;DNA binding;DNA helicase activity;single-stranded DNA binding;ATP-dependent DNA helicase activity;helicase activity;protein binding;ATP binding;ATP-dependent helicase activity;DNA-dependent ATPase activity;zinc ion binding;four-way junction helicase activity;ATPase activity;annealing helicase activity;protein homodimerization activity;ATP-dependent 3'-5' DNA helicase activity;G-quadruplex DNA binding;forked DNA-dependent helicase activity;telomeric D-loop binding;telomeric G-quadruplex DNA binding;8-hydroxy-2'-deoxyguanosine DNA binding