LRRC27

Chr 10

leucine rich repeat containing 27

NCBI Gene: 80313 ENSG00000148814 UniProt: Q9C0I9

LRRC27 encodes a leucine-rich repeat-containing protein involved in ciliary function and structure. Mutations cause autosomal recessive primary ciliary dyskinesia, characterized by chronic respiratory infections, situs inversus, and male infertility due to defective ciliary motility. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.40

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.40LOEUF

pLI 0.000

Z-score -0.03

OE 1.01 (0.74–1.40)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.59Z-score

OE missense 1.09 (1.00–1.20)

334 obs / 305.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.01 (0.74–1.40)

0≤0.351.4

Missense OE?1.09 (1.00–1.20)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 26 / 25.8Missense obs/exp: 334 / 305.0Syn Z: -1.11

Background carrier burden — how many people carry a rare variant somewhere in LRRC27?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 54

885 rare PASS variants

Rare truncating (LoF)

1 in 290

162 rare PASS variants

Rare synonymous (reference)

1 in 110

292 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRRC27. 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 90	1 in 570
South Asian	~43k	1 in 45	1 in 280
Remaining (unassigned)	~30k	1 in 37	1 in 300
European (Finnish)	~27k	1 in 190	1 in 3,200
Admixed American	~22k	1 in 47	1 in 590
African / African American	~21k	1 in 47	1 in 330
East Asian	~20k	1 in 72	1 in 400
Ashkenazi Jewish	~13k	1 in 300	1 in 1,200
Middle Eastern	~2,884	1 in 41	1 in 390

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 10.? see exons ↓