BLM

Chr 15AR

BLM RecQ like helicase

The BLM protein is an ATP-dependent DNA helicase that unwinds double-stranded DNA, participates in DNA replication and repair, and resolves complex DNA structures including Holliday junctions and G-quadruplex DNA to maintain genome stability. Biallelic mutations cause Bloom syndrome, an autosomal recessive disorder characterized by growth deficiency, microcephaly, and immunodeficiency. The gene is highly constrained against loss-of-function variants in the population, reflecting its essential cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.751 OMIM phenotype
Clinical SummaryBLM
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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.
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.000
Z-score 3.14
OE 0.56 (0.430.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.89Z-score
OE missense 0.91 (0.850.97)
664 obs / 731.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.430.75)
00.351.4
Missense OE0.91 (0.850.97)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 34 / 60.3Missense obs/exp: 664 / 731.5Syn Z: 1.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBLM-related Bloom syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.2994th %ile
LOF
0.3841th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
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
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
StrokeGenetic Association Studies

Genetic Variants in Stroke

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

Genetic Susceptibility to Bladder Cancer

ACTIVE NOT RECRUITING
NCT00848289M.D. Anderson Cancer CenterStarted 1998-02-10
Interviews
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
Clinical Literature
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