LYST

Chr 1AR

lysosomal trafficking regulator

Also known as: CHS, CHS1, Mauve

NCBI Gene: 1130ENSG00000143669UniProt: Q99698

This gene encodes a protein that regulates intracellular protein trafficking in endosomes, and may be involved in pigmentation. Mutations in this gene are associated with Chediak-Higashi syndrome, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants, though the full-length nature of some of these variants has not been determined. [provided by RefSeq, Apr 2013]

Primary Disease Associations & Inheritance

Chediak-Higashi syndromeMIM #214500
AR
595
ClinVar variants
81
Pathogenic / LP
0.02
pLI score
1
Active trials
Clinical Summary— LYST
🧬
Gene-Disease Validity (ClinGen)
Chediak-Higashi syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
81 Pathogenic / Likely Pathogenic· 224 VUS of 595 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.31LOEUF
pLI 0.015
Z-score 9.58
OE 0.24 (0.19–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
1.41Z-score
OE missense 0.91 (0.87–0.95)
1758 obs / 1932.1 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.0.24 (0.19–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.87–0.95)
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.1.01
0≤1.21.6
LoF obs/exp: 44 / 184.4Missense obs/exp: 1758 / 1932.1Syn Z: -0.23

ClinVar Variant Classifications

595 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic41
VUS224
Likely Benign287
Benign2
Conflicting1
40
Pathogenic
41
Likely Pathogenic
224
VUS
287
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
0
22
0
40
Likely Pathogenic
25
0
16
0
41
VUS
1
206
16
1
224
Likely Benign
0
3
99
185
287
Benign
0
0
1
1
2
Conflicting
—1
Total44209154187595

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

View in ClinVar →

Protein Context — Lollipop Plot

LYST · protein map & ClinVar variants

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

Gene2Phenotype Curations

LYST-related Chediak-Higashi syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Chediak-Higashi syndrome

MIM #214500

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — LYST
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pediatric hemophagocytic lymphohistiocytosis.
Canna SW et al.·Blood
2020Review
Chediak-Higashi syndrome.
Talbert ML et al.·Curr Opin Hematol
2023Review
Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders.
Gadoury-Levesque V et al.·Blood Adv
2020Cohort
Chediak-Higashi syndrome.
Kaplan J et al.·Curr Opin Hematol
2008Review
Chedíak-Higashi Syndrome: Hair-to-toe spectrum.
Greene S et al.·Semin Pediatr Neurol
2024Review
Spectrum of LYST mutations in Chediak-Higashi syndrome: a report of novel variants and a comprehensive review of the literature.
Morimoto M et al.·J Med Genet
2024Review
Angeborene hämophagozytische Lymphohistiozytose (HLH).
Pachlopnik Schmid J et al.·Klin Padiatr
2010Review
LYST deficiency impairs autophagic lysosome reformation in neurons and alters lysosome number and size.
Serra-Vinardell J et al.·Cell Mol Life Sci
2023
Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells.
Konigsberg IR et al.·Respir Res
2024
Peripheral neuropathy and parkinsonism: a large clinical and pathogenic spectrum.
Vital A et al.·J Peripher Nerv Syst
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Lymphatic System Transfer (LYST) with Pedicled SCIP for Patients with Lymphedema and Concomitant Chronic Venous Disease.
Xu KY et al.·Plast Reconstr Surg
2026Cohort
A murine model lacking Lyst recapitulates Chediak-Higashi syndrome with an earlier-onset neurodegenerative phenotype.
Greene S et al.·Commun Biol
2025🔓 Open AccessFunctional
Comprehensive analysis of a novel LYST mutation in a Tunisian patient with Chediak-Higashi syndrome.
Amri Y et al.·BMC Med Genomics
2025🔓 Open Access
SQST-1/p62-regulated SKN-1/Nrf mediates a phagocytic stress response via transcriptional activation of lyst-1/LYST.
Elkhalil A et al.·PLoS Genet
2025🔓 Open Access
The ASPARAGINE-RICH PROTEIN-LYST-INTERACTING PROTEIN5 complex regulates noncanonical AUTOPHAGY8 degradation in Arabidopsis.
Wu Y et al.·Plant Physiol
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Chediak-Higashi Syndrome

Study of Chediak-Higashi Syndrome

RECRUITING
NCT00005917National Human Genome Research Institute (NHGRI)Started 2002-09-10

External Resources

Links to major genomics databases and tools