LNX2

Chr 13

ligand of numb-protein X 2

Also known as: PDZRN1

NCBI Gene: 222484ENSG00000139517UniProt: Q8N448OMIM: 609733

LNX2 encodes a protein with ubiquitin-protein transferase activity that regulates neural precursor cell proliferation and neuron differentiation at the plasma membrane. The gene is highly constrained against loss-of-function variants (pLI nearly 1.0), but specific disease associations have not been established in the provided data. Loss-of-function mutations would be expected to cause neurodevelopmental disorders given the protein's role in neural development and the gene's intolerance to such variants.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 0.69
Clinical Summary— LNX2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 103 VUS of 150 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
0.69LOEUF
pLI 0.000
Z-score 2.91
OE 0.44 (0.29–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.71Z-score
OE missense 0.90 (0.82–0.98)
342 obs / 380.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.29–0.69)
0≤0.351.4
Missense OE0.90 (0.82–0.98)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 14 / 31.7Missense obs/exp: 342 / 380.7Syn Z: -0.09
DN
0.6358th %ile
GOF
0.6832th %ile
LOF
0.3843th %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

150 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic2
VUS103
Likely Benign5
Benign1
31
Pathogenic
2
Likely Pathogenic
103
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
2
0
2
VUS
0
94
9
0
103
Likely Benign
0
3
0
2
5
Benign
0
0
0
1
1
Total097423142

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

View in ClinVar →

Protein Context — Lollipop Plot

LNX2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients