LRRC70

Chr 5

leucine rich repeat containing 70

Also known as: SLRN

NCBI Gene: 100130733 ENSG00000186105 UniProt: Q7Z2Q7

LRRC70 encodes a plasma membrane protein that renders cells highly sensitive to activation by cytokines and lipopolysaccharide. Mutations cause autosomal recessive primary immunodeficiency with defective lymphocyte activation and susceptibility to infection. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF >1), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

Involved in positive regulation of response to cytokine stimulus. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.11

Clinical Summary— LRRC70

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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

83 VUS of 87 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?

1.11LOEUF

pLI 0.000

Z-score 1.20

OE 0.70 (0.45–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

2.52Z-score

OE missense 0.59 (0.52–0.67)

176 obs / 298.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.70 (0.45–1.11)

0≤0.351.4

Missense OE?0.59 (0.52–0.67)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 13 / 18.6Missense obs/exp: 176 / 298.7Syn Z: 1.98

This gene — mechanism propensity

0.6937th %ile

GOF

0.75top 25%

LOF

0.3067th %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

87 submitted variants in ClinVar

ClinVar

Classification Summary

VUS83

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	83	83
Likely Benign	4	4
Benign	0	0
Total	87	87

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap LRRC70 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →