LRRC70

Chr 5

leucine rich repeat containing 70

Also known as: SLRN

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
MultiplemechanismLOEUF 1.11
Clinical SummaryLRRC70
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.11LOEUF
pLI 0.000
Z-score 1.20
OE 0.70 (0.451.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
2.52Z-score
OE missense 0.59 (0.520.67)
176 obs / 298.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.70 (0.451.11)
00.351.4
Missense OE0.59 (0.520.67)
00.61.4
Synonymous OE0.76
01.21.6
LoF obs/exp: 13 / 18.6Missense obs/exp: 176 / 298.7Syn Z: 1.98
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LRRC70 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found