BLM

BLM RecQ like helicase, the group of RecQ like helicases

Basic information

Region (hg38): 15:90717345-90816166

Links

ENSG00000197299 ∙ NCBI:641 ∙ OMIM:604610 ∙ HGNC:1058 ∙ Uniprot:P54132 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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

Clinical Genomic Database

Source: CGD

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
Variants may also be related to risk of malignancy in the general poulation

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BLM gene.

• Bloom syndrome (3112 variants)
• Hereditary cancer-predisposing syndrome (1954 variants)
• not provided (339 variants)
• not specified (162 variants)
• Hereditary breast ovarian cancer syndrome (18 variants)
• BLM-related condition (14 variants)
• Ovarian cancer (11 variants)
• Hereditary cancer (7 variants)
• - (5 variants)
• Inborn genetic diseases (4 variants)
• Microcephaly (3 variants)
• Familial cancer of breast;Endometrial carcinoma;Colorectal cancer (1 variants)
• See cases (1 variants)
• Hereditary disease (1 variants)
• Olaparib response (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			15	770	4	789
missense	1	3	1854	25	6	1889
nonsense	88	27	4			119
start loss		2				2
frameshift	146	91	6	1	1	245
inframe indel			36	1		37
splice donor/acceptor (+/-2bp)	2	62	4			68
splice region		3	59	92	4	158
non coding		2	27	271	52	352
Total	237	187	1946	1068	63

Highest pathogenic variant AF is 0.000171

Variants in BLM

This is a list of pathogenic ClinVar variants found in the BLM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-90717375-G-T		Bloom syndrome	Uncertain significance (Jan 13, 2018)
15-90717380-C-T		Bloom syndrome	Uncertain significance (Jan 13, 2018)
15-90717386-T-A		Bloom syndrome	Uncertain significance (Jan 12, 2018)
15-90717412-G-C		Bloom syndrome	Uncertain significance (Jan 12, 2018)
15-90717416-C-T		Bloom syndrome	Uncertain significance (Jan 12, 2018)
15-90717440-G-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Feb 19, 2021)
15-90717456-G-C		not specified • Bloom syndrome	Benign (Dec 04, 2013)
15-90717714-G-C			Benign (Jun 23, 2018)
15-90717735-G-C			Benign (Jun 23, 2018)
15-90747136-G-C			Benign (Jun 23, 2018)
15-90747387-A-T		Bloom syndrome	Uncertain significance (Sep 04, 2020)
15-90747389-G-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 23, 2023)
15-90747393-A-C		Bloom syndrome	Likely pathogenic (May 01, 2018)
15-90747393-A-G		Bloom syndrome	Uncertain significance (Jun 25, 2023)
15-90747394-T-C		Bloom syndrome • Hereditary cancer-predisposing syndrome	Likely pathogenic (Jan 12, 2023)
15-90747396-G-T		Bloom syndrome • Hereditary cancer-predisposing syndrome	Uncertain significance (Feb 25, 2024)
15-90747397-C-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 04, 2021)
15-90747399-G-A		Bloom syndrome	Uncertain significance (Jul 19, 2022)
15-90747399-G-GCT		Bloom syndrome	Likely pathogenic (Feb 12, 2023)
15-90747401-T-C		Bloom syndrome • Hereditary cancer-predisposing syndrome	Likely benign (May 26, 2023)
15-90747402-G-A		Bloom syndrome	Uncertain significance (May 29, 2022)
15-90747402-G-C		Bloom syndrome	Uncertain significance (Nov 13, 2021)
15-90747402-G-T		Bloom syndrome	Uncertain significance (Aug 26, 2021)
15-90747403-T-A		Bloom syndrome • Hereditary cancer-predisposing syndrome	Uncertain significance (Nov 27, 2023)
15-90747403-T-C		not specified • Bloom syndrome • Hereditary cancer-predisposing syndrome • Hereditary cancer • BLM-related disorder	Conflicting classifications of pathogenicity (Jan 31, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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