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…

MultiplemechanismLOEUF 1.40

Clinical Summary— LRRC27

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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

87 VUS of 127 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?

1.40LOEUF

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

This gene — mechanism propensity

0.7229th %ile

GOF

0.81top 10%

LOF

0.3261th %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

127 submitted variants in ClinVar

ClinVar

Classification Summary

VUS87

Likely Benign16

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	86	87
Likely Benign	0	16	16
Benign	0	1	1
Total	1	103	104

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

View in ClinVar →

98 pathogenic / likely-pathogenic (of 110) ClinVar copy-number / structural variants overlap LRRC27 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →