LYST

Chr 1

lysosomal trafficking regulator

Also known as: CHS, CHS1, Mauve

The protein regulates intracellular vesicle trafficking and fission, particularly of lysosomes and lytic granules, and controls phagosome maturation and TLR-mediated inflammatory responses in immune cells. Mutations cause Chediak-Higashi syndrome, a lysosomal storage disorder inherited in an autosomal recessive pattern. The disease results from loss of protein function, leading to defective vesicle trafficking and immune cell dysfunction.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.31
Clinical SummaryLYST
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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.
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ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 169 VUS of 400 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — LYST
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.015
Z-score 9.58
OE 0.24 (0.190.31)
Highly constrained

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

Missense Constraint
1.41Z-score
OE missense 0.91 (0.870.95)
1758 obs / 1932.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.190.31)
00.351.4
Missense OE0.91 (0.870.95)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 44 / 184.4Missense obs/exp: 1758 / 1932.1Syn Z: -0.23

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic8
VUS169
Likely Benign149
Benign1
23
Pathogenic
8
Likely Pathogenic
169
VUS
149
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
0
2
0
23
Likely Pathogenic
8
0
0
0
8
VUS
2
158
8
1
169
Likely Benign
0
5
48
96
149
Benign
0
0
0
1
1
Total311635898350

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗