LY6H

Chr 8

lymphocyte antigen 6 family member H

Also known as: NMLY6

NCBI Gene: 4062ENSG00000176956UniProt: O94772

The LY6H protein modulates nicotinic acetylcholine receptor activity by inhibiting alpha-3:beta-4-containing receptors and affecting intracellular trafficking of alpha-7-containing receptors. Currently, no human diseases have been definitively associated with LY6H mutations in the medical literature. The gene shows tolerance to loss-of-function variants with a low constraint score (pLI = 0.17, LOEUF = 1.0).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
58
P/LP submissions
0%
P/LP missense
1.00
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— LY6H
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 32 VUS of 92 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
1.00LOEUF
pLI 0.168
Z-score 1.58
OE 0.32 (0.13–1.00)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.61Z-score
OE missense 0.81 (0.67–1.00)
67 obs / 82.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.13–1.00)
0≤0.351.4
Missense OE0.81 (0.67–1.00)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 2 / 6.3Missense obs/exp: 67 / 82.5Syn Z: -0.18
DN
0.6358th %ile
GOF
0.6540th %ile
LOF
0.2774th %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

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic4
VUS32
Likely Benign1
54
Pathogenic
4
Likely Pathogenic
32
VUS
1
Likely 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
24
8
0
32
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total02566091

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

View in ClinVar →

Protein Context — Lollipop Plot

LY6H · protein map & ClinVar variants

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

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 3 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