LRRC19

Chr 9

leucine rich repeat containing 19

NCBI Gene: 64922 ENSG00000184434 UniProt: Q9H756 OMIM: 619068

LRRC19 encodes a pathogen-recognition receptor that mediates NF-kappaB signaling pathway activation and induces pro-inflammatory cytokine expression, particularly important for preventing uropathogenic bacterial infections in the kidney and regulating host-microbiota interactions in the gut. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.777), and no established Mendelian disease associations have been reported to date. Clinical significance of LRRC19 variants in pediatric patients remains unclear given the lack of documented disease phenotypes.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable signaling receptor activity. Acts upstream of or within positive regulation of non-canonical NF-kappaB signal transduction. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.78

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -0.72

OE 1.21 (0.82–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.44Z-score

OE missense 1.09 (0.97–1.23)

193 obs / 176.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.21 (0.82–1.78)

0≤0.351.4

Missense OE?1.09 (0.97–1.23)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 16 / 13.2Missense obs/exp: 193 / 176.7Syn Z: -1.45

Background carrier burden — how many people carry a rare variant somewhere in LRRC19?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

494 rare PASS variants

Rare truncating (LoF)

1 in 1,700

84 rare PASS variants

Rare synonymous (reference)

1 in 610

196 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRRC19. 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 160	1 in 2,400
South Asian	~43k	1 in 92	1 in 1,400
Remaining (unassigned)	~30k	1 in 82	1 in 830
European (Finnish)	~27k	1 in 310	1 in 4,200
Admixed American	~22k	1 in 110	1 in 630
African / African American	~21k	1 in 82	1 in 420
East Asian	~20k	1 in 140	1 in 680
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 5,600
Middle Eastern	~2,884	1 in 100	1 in 540

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 4.? see exons ↓