LRRC52

Chr 1

leucine rich repeat containing 52

NCBI Gene: 440699 ENSG00000162763 UniProt: Q8N7C0 OMIM: 615218

This protein functions as an auxiliary subunit that modulates the gating properties of large-conductance calcium-activated potassium (BK) channels and KCNU1 channels, shifting their voltage dependence of activation. Based on current databases, no definitive disease associations have been established for pathogenic variants in this gene. The gene shows minimal constraint against loss-of-function variation (pLI near 0, LOEUF 1.66), suggesting haploinsufficiency may be tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables potassium channel activator activity; transmembrane transporter binding activity; and voltage-gated potassium channel activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.66

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.000

Z-score 0.13

OE 0.95 (0.56–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.88–1.13)

173 obs / 174.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.95 (0.56–1.66)

0≤0.351.4

Missense OE?0.99 (0.88–1.13)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 8 / 8.4Missense obs/exp: 173 / 174.4Syn Z: -1.27

Background carrier burden — how many people carry a rare variant somewhere in LRRC52?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

420 rare PASS variants

Rare truncating (LoF)

1 in 1,900

55 rare PASS variants

Rare synonymous (reference)

1 in 220

194 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRRC52. 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 240	1 in 2,000
South Asian	~43k	1 in 150	1 in 1,600
Remaining (unassigned)	~30k	1 in 96	1 in 2,500
European (Finnish)	~27k	1 in 260	1 in 840
Admixed American	~22k	1 in 160	1 in 1,400
African / African American	~21k	1 in 150	1 in 2,800
East Asian	~20k	1 in 250	1 in 1,000
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 180	≈ 1 in 1,400

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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓