LRFN2

Chr 6

leucine rich repeat and fibronectin type III domain containing 2

Also known as: FIGLER2, KIAA1246, SALM1

NCBI Gene: 57497ENSG00000156564UniProt: Q9ULH4

Predicted to be involved in modulation of chemical synaptic transmission and regulation of postsynapse organization. Predicted to be located in plasma membrane. Predicted to be active in several cellular components, including Schaffer collateral - CA1 synapse; cell surface; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2025]

118
ClinVar variants
6
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— LRFN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 107 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.71LOEUF
pLI 0.014
Z-score 2.41
OE 0.36 (0.20–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.60Z-score
OE missense 0.80 (0.74–0.87)
406 obs / 507.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.20–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.74–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 6 / 16.6Missense obs/exp: 406 / 507.7Syn Z: -1.02

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS107
Likely Benign4
Benign1
6
Pathogenic
107
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
106
1
0
107
Likely Benign
0
1
0
3
4
Benign
0
0
0
1
1
Total010774118

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

View in ClinVar →

Protein Context — Lollipop Plot

LRFN2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cone Synaptic function is modulated by the leucine rich repeat (LRR) adhesion molecule LRFN2.
Hasan N et al.·eNeuro
2024🔓 Open Access
Bladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8+ T cell infiltration and functional transition.
Yu A et al.·J Immunother Cancer
2023🔓 Open AccessFunctional
LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/β-Catenin and NF-κB signaling pathway.
Zhou Y et al.·Cancer Sci
2022🔓 Open Access
Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2.
McMillan KJ et al.·Elife
2021🔓 Open Access
Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice.
Maekawa R et al.·PLoS One
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools