TOP6BL

Chr 11AR

TOP6B like initiator of meiotic double strand breaks

Also known as: C11orf80, HYDM4, TOPOVIBL

NCBI Gene: 79703 ENSG00000173715 UniProt: Q8N6T0 OMIM: 616109

The protein is a component of a topoisomerase 6 complex that works with SPO11 to create DNA double-strand breaks essential for initiating meiotic recombination. Biallelic mutations cause recurrent hydatidiform moles, a form of gestational trophoblastic disease affecting pregnancy outcomes. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hydatidiform mole, recurrent, 4MIM #618432

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hydatidiform mole, recurrent; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.96

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.72

OE 0.65 (0.45–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.83Z-score

OE missense 0.87 (0.78–0.96)

263 obs / 303.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.45–0.96)

0≤0.351.4

Missense OE?0.87 (0.78–0.96)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 18 / 27.8Missense obs/exp: 263 / 303.5Syn Z: -0.61

Background carrier burden — how many people carry a rare variant somewhere in TOP6BL?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

834 rare PASS variants

Rare truncating (LoF)

1 in 810

182 rare PASS variants

Rare synonymous (reference)

1 in 180

284 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TOP6BL. 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 110	1 in 1,200
South Asian	~43k	1 in 78	1 in 270
Remaining (unassigned)	~30k	1 in 120	1 in 1,600
European (Finnish)	~27k	1 in 300	1 in 920
Admixed American	~22k	1 in 94	1 in 500
African / African American	~21k	1 in 59	1 in 300
East Asian	~20k	1 in 83	1 in 880
Ashkenazi Jewish	~13k	1 in 870	1 in 1,000
Middle Eastern	~2,884	1 in 92	none seen

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): 13 of 14 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 14.? see exons ↓