The LYNX1 protein is a membrane-bound modulator of nicotinic acetylcholine receptors that prevents excessive neuronal excitation by enhancing receptor desensitization and regulating receptor trafficking to the cell surface. Mutations in LYNX1 cause autosomal dominant epileptic encephalopathy with onset in infancy, characterized by seizures and developmental delay. The gene shows tolerance to loss-of-function variants, suggesting the pathogenic variants may act through alternative mechanisms.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
58
P/LP submissions
0%
P/LP missense
1.35
LOEUF
DN
Mechanism· predicted
Clinical SummaryLYNX1
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 23 VUS of 90 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.026
Z-score 1.03
OE 0.53 (0.241.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.97Z-score
OE missense 0.70 (0.560.87)
57 obs / 81.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.241.35)
00.351.4
Missense OE0.70 (0.560.87)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 3 / 5.6Missense obs/exp: 57 / 81.8Syn Z: 0.05
DN
0.73top 25%
GOF
0.5563th %ile
LOF
0.2092th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

90 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic4
VUS23
Likely Benign1
Benign1
54
Pathogenic
4
Likely Pathogenic
23
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
4
0
4
VUS
0
11
12
0
23
Likely Benign
0
0
1
0
1
Benign
0
0
0
1
1
Total01171183

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

View in ClinVar →

Protein Context — Lollipop Plot

LYNX1 · 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.

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Clinical Literature
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