BLM

Chr 15AR

BLM RecQ like helicase

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

NCBI Gene: 641 ENSG00000197299 UniProt: P54132 OMIM: 210900

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bloom syndromeMIM #210900

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

667

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — BLM

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.000

Z-score 3.14

OE 0.56 (0.43–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.89Z-score

OE missense 0.91 (0.85–0.97)

664 obs / 731.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.43–0.75)

0≤0.351.4

Missense OE?0.91 (0.85–0.97)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 34 / 60.3Missense obs/exp: 664 / 731.5Syn Z: 1.14

Background carrier burden — how many people carry a rare variant somewhere in BLM?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

1,647 rare PASS variants

Rare truncating (LoF)

1 in 350

257 rare PASS variants

Rare synonymous (reference)

1 in 83

578 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BLM. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 53	1 in 360
South Asian	~43k	1 in 32	1 in 480
Remaining (unassigned)	~30k	1 in 29	1 in 500
European (Finnish)	~27k	1 in 97	1 in 1,200
Admixed American	~22k	1 in 32	1 in 440
African / African American	~21k	1 in 36	1 in 390
East Asian	~20k	1 in 35	1 in 320
Ashkenazi Jewish	~13k	1 in 140	1 in 1,800
Middle Eastern	~2,884	1 in 45	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 20 of 21 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: all 21.? see exons ↓