LRRC40

Chr 1

leucine rich repeat containing 40

Also known as: dJ677H15.1

NCBI Gene: 55631 ENSG00000066557 UniProt: Q9H9A6

The LRRC40 protein is predicted to function in intracellular signal transduction and is located in cellular membranes. Mutations in this gene have not been definitively associated with human disease based on the available information. The gene shows very low constraint against loss-of-function variants (pLI near zero, LOEUF 1.35), suggesting tolerance to protein disruption.

ResearchSummary from RefSeq

Predicted to be involved in intracellular signal transduction. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.35

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.000

Z-score -0.01

OE 1.00 (0.75–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.97 (0.88–1.07)

287 obs / 296.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.00 (0.75–1.35)

0≤0.351.4

Missense OE?0.97 (0.88–1.07)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 31 / 30.9Missense obs/exp: 287 / 296.0Syn Z: 0.84

Background carrier burden — how many people carry a rare variant somewhere in LRRC40?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

733 rare PASS variants

Rare truncating (LoF)

1 in 860

161 rare PASS variants

Rare synonymous (reference)

1 in 240

270 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRRC40. 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 74	1 in 940
South Asian	~43k	1 in 83	1 in 650
Remaining (unassigned)	~30k	1 in 63	1 in 860
European (Finnish)	~27k	1 in 130	1 in 520
Admixed American	~22k	1 in 52	1 in 870
African / African American	~21k	1 in 71	1 in 730
East Asian	~20k	1 in 94	1 in 620
Ashkenazi Jewish	~13k	1 in 410	1 in 2,600
Middle Eastern	~2,884	1 in 65	1 in 560

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 15 coding exons well covered in gnomAD exomes; exons 3, 5, 6, 7, 8 and 6 more marginal. Genomes: all 15.? see exons ↓