BLM

Chr 15AR

BLM RecQ like helicase

Also known as: BS, MGRISCE1, RECQ2, RECQL2, RECQL3

NCBI Gene: 641ENSG00000197299UniProt: P54132

The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families. [provided by RefSeq, May 2020]

Primary Disease Associations & Inheritance

Bloom syndromeMIM #210900
AR
582
ClinVar variants
57
Pathogenic / LP
0.00
pLI score
8
Active trials
Clinical Summary— BLM
🧬
Gene-Disease Validity (ClinGen)
Bloom syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
57 Pathogenic / Likely Pathogenic· 376 VUS of 582 total submissions
💊
Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.75LOEUF
pLI 0.000
Z-score 3.14
OE 0.56 (0.43–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.89Z-score
OE missense 0.91 (0.85–0.97)
664 obs / 731.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.43–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.85–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 34 / 60.3Missense obs/exp: 664 / 731.5Syn Z: 1.14

ClinVar Variant Classifications

582 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic13
VUS376
Likely Benign143
Benign1
Conflicting5
44
Pathogenic
13
Likely Pathogenic
376
VUS
143
Likely Benign
1
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
0
16
0
44
Likely Pathogenic
10
0
3
0
13
VUS
2
348
24
2
376
Likely Benign
1
1
55
86
143
Benign
0
0
1
0
1
Conflicting
—5
Total413499988582

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BLM · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

BLM-related Bloom syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
BLOOM SYNDROME; BLM
MIM #210900 · #

Bloom syndrome

MIM #210900

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — BLM
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nicotinamide phosphoribosyltransferase prompts bleomycin-induced pulmonary fibrosis by driving macrophage M2 polarization in mice.
Chen Y et al.·Theranostics
2024
CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade.
Rogers CM et al.·Science
2025
Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis.
Prêle CM et al.·Eur Respir J
2022
Pulmonary fibrosis model of mice induced by different administration methods of bleomycin.
Gul A et al.·BMC Pulm Med
2023Functional
MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program.
Wang Y et al.·Sci Adv
2021
Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions.
Della Latta V et al.·Pharmacol Res
2015Review
Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease.
Facchin S et al.·Neurogastroenterol Motil
2020Cohort
Ficolin B secreted by alveolar macrophage exosomes exacerbates bleomycin-induced lung injury via ferroptosis through the cGAS-STING signaling pathway.
Wu X et al.·Cell Death Dis
2023
Bleomycin (review).
Bishun NP et al.·Oncology
1978Review
Loss of PTEN induces lung fibrosis via alveolar epithelial cell senescence depending on NF-κB activation.
Tian Y et al.·Aging Cell
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Sickle Cell Disease (SCD)

Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients

ACTIVE NOT RECRUITING
NCT03814746Phase PHASE3Novartis PharmaceuticalsStarted 2019-07-26
Crizanlizumab (SEG101)Placebo
Bladder Cancer

Genetic Susceptibility to Bladder Cancer

ACTIVE NOT RECRUITING
NCT00848289M.D. Anderson Cancer CenterStarted 1998-02-10
Interviews
StrokeGenetic Association Studies

Genetic Variants in Stroke

NOT YET RECRUITING
NCT07186517Hospital Moinhos de VentoStarted 2025-10-01
Breast CancerProstate Cancer

Onco-Genomas Brasil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System

RECRUITING
NCT05306600Hospital Moinhos de VentoStarted 2022-11-09
whole exome and whole genome sequencing analysis
Cardiomyopathy, HypertrophicCardiomyopathy, DilatedCardiomyopathy Restrictive

National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil's Unified Health System Through a Multicenter Registry

RECRUITING
NCT06546137Hospital do CoracaoStarted 2025-04-30
whole genome sequencing
Gastric CancerGastroEsophageal Cancer

Study of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers

ACTIVE NOT RECRUITING
NCT05379972Phase PHASE2University of Colorado, DenverStarted 2023-01-12
PembrolizumabOlaparibStereotactic Body Radiation Therapy
Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING
NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01
ST-01156
Metastatic Pancreatic Ductal AdenocarcinomaHomologous Recombination Deficiency (HRD)

A Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy

ACTIVE NOT RECRUITING
NCT04666740Phase PHASE2Memorial Sloan Kettering Cancer CenterStarted 2020-12-18
PembrolizumabOlaparib

External Resources

Links to major genomics databases and tools