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…

MultiplemechanismLOEUF 1.66

Clinical Summary— LRRC52

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 VUS of 47 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.6938th %ile

GOF

0.74top 25%

LOF

0.2873th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	42	0	42
Likely Benign	2	0	2
Benign	1	1	2
Total	45	1	46

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap LRRC52 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →