LYST

Summary

LYST (lysosomal trafficking regulator, HGNC:1968) is a protein-coding gene on chromosome 1q42.3, encoding Lysosomal-trafficking regulator (Q99698). Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes.

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.

Source: NCBI Gene 1130 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Chediak-Higashi syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 3,992 total — 137 pathogenic, 107 likely-pathogenic
• Phenotypes (HPO): 104
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000081

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1968
Approved symbol	LYST
Name	lysosomal trafficking regulator
Location	1q42.3
Locus type	gene with protein product
Status	Approved
Aliases	CHS, Mauve
Ensembl gene	ENSG00000143669
Ensembl biotype	protein_coding
OMIM	606897
Entrez	1130

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 12 protein_coding, 7 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined, 5 retained_intron

ENST00000389793, ENST00000461526, ENST00000462376, ENST00000465349, ENST00000468107, ENST00000468626, ENST00000473037, ENST00000475277, ENST00000487530, ENST00000489585, ENST00000492844, ENST00000697178, ENST00000697179, ENST00000697180, ENST00000697181, ENST00000697182, ENST00000697183, ENST00000697184, ENST00000697185, ENST00000697186, ENST00000697235, ENST00000697236, ENST00000697237, ENST00000697238, ENST00000697239, ENST00000697240, ENST00000697241, ENST00000697242, ENST00000697248, ENST00000697249

RefSeq mRNA: 2 — MANE Select: NM_000081 NM_000081, NM_001301365

CCDS: CCDS31062

Canonical transcript exons

ENST00000389793 — 53 exons

Exon	Start	End
ENSE00000961469	235758972	235759599
ENSE00001423778	235866843	235866906
ENSE00001424390	235833578	235833667
ENSE00001509893	235661041	235663078
ENSE00003458799	235762720	235762851
ENSE00003461154	235720661	235720905
ENSE00003475755	235741422	235741628
ENSE00003477451	235712057	235712197
ENSE00003484512	235774913	235775086
ENSE00003506340	235830226	235830424
ENSE00003508546	235800871	235801097
ENSE00003510003	235791699	235792125
ENSE00003522261	235733503	235733691
ENSE00003523539	235788701	235788845
ENSE00003526789	235686949	235687047
ENSE00003528984	235781927	235782087
ENSE00003529091	235802908	235803064
ENSE00003530827	235702747	235702977
ENSE00003537661	235693350	235693486
ENSE00003542717	235777063	235777308
ENSE00003543955	235677480	235677619
ENSE00003551321	235800320	235800386
ENSE00003556676	235731032	235731177
ENSE00003567871	235664465	235664621
ENSE00003571882	235808455	235810534
ENSE00003581883	235709091	235709308
ENSE00003586687	235729596	235729657
ENSE00003590346	235773842	235773991
ENSE00003593340	235787200	235787373
ENSE00003594713	235804504	235804665
ENSE00003599764	235733830	235733906
ENSE00003603021	235697083	235697272
ENSE00003618959	235728076	235728131
ENSE00003638964	235780865	235781055
ENSE00003648042	235766079	235766277
ENSE00003649483	235724028	235724180
ENSE00003654583	235663984	235664055
ENSE00003659400	235716712	235716778
ENSE00003659472	235770160	235770297
ENSE00003661514	235812971	235813061
ENSE00003674489	235677091	235677188
ENSE00003676905	235805743	235806772
ENSE00003684084	235793503	235793612
ENSE00003691151	235730847	235730943
ENSE00003693863	235715201	235715357
ENSE00003711526	235751210	235751362
ENSE00003717310	235752005	235752171
ENSE00003726648	235755478	235755647
ENSE00003730070	235743979	235744157
ENSE00003733869	235757281	235757458
ENSE00003735459	235746336	235746527
ENSE00003745038	235734483	235734659
ENSE00003747123	235753044	235753274

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0797 / max 843.2844, expressed in 1564 samples.

FANTOM5 promoters (23 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18172	6.5410	1221
18173	2.8195	911
18191	1.0013	322
18175	0.8042	431
18171	0.6281	172
18174	0.2906	130
18170	0.2064	48
18180	0.1546	50
18169	0.0887	28
18179	0.0863	24

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.58	gold quality
mononuclear cell	CL:0000842	97.12	gold quality
leukocyte	CL:0000738	96.90	gold quality
nipple	UBERON:0002030	96.39	gold quality
trabecular bone tissue	UBERON:0002483	96.02	gold quality
bone marrow	UBERON:0002371	94.83	gold quality
blood	UBERON:0000178	94.37	gold quality
pylorus	UBERON:0001166	94.23	gold quality
bone marrow cell	CL:0002092	94.10	gold quality
upper leg skin	UBERON:0004262	93.61	gold quality
cardia of stomach	UBERON:0001162	93.37	gold quality
granulocyte	CL:0000094	93.33	gold quality
calcaneal tendon	UBERON:0003701	93.33	gold quality
colonic epithelium	UBERON:0000397	92.01	gold quality
sperm	CL:0000019	91.36	gold quality
saphenous vein	UBERON:0007318	91.34	gold quality
middle temporal gyrus	UBERON:0002771	90.44	gold quality
male germ cell	CL:0000015	90.32	gold quality
skin of hip	UBERON:0001554	90.22	gold quality
thymus	UBERON:0002370	89.98	gold quality
urethra	UBERON:0000057	89.63	gold quality
periodontal ligament	UBERON:0008266	88.93	gold quality
skin of abdomen	UBERON:0001416	88.80	gold quality
sural nerve	UBERON:0015488	88.62	gold quality
inferior vagus X ganglion	UBERON:0005363	88.60	gold quality
tendon	UBERON:0000043	88.43	gold quality
visceral pleura	UBERON:0002401	88.39	gold quality
dorsal root ganglion	UBERON:0000044	87.97	gold quality
corpus callosum	UBERON:0002336	87.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.90	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	36.38
E-CURD-122	yes	26.43
E-MTAB-6678	yes	23.09
E-CURD-112	yes	22.60
E-MTAB-9067	yes	16.07
E-CURD-46	yes	9.64
E-GEOD-81383	no	3032.52
E-MTAB-6075	no	2140.46
E-CURD-10	no	385.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting LYST, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-607	99.97	73.62	5593

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 23)

• Childhood, adolescent, and adult forms of Chediak-Higashi syndrome correlate with different genotypes. (PMID:11857544)
• The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins. (PMID:11984006)
• results suggest that the Beige protein interacts with at least two different partners and that the Beige protein affects cellular events, such as nuclear PtdIns(4,5)P2 localization, in addition to lysosome size (PMID:12753649)
• two newly described nonsense mutations are expected to give rise to a severe phenotype and the patient had absolutely no cytotoxicity by natural killer cells or cytotoxic lymphocytes (PMID:15896657)
• CHS1/LYST protein is involved in either vesicle fusion or fission. CHS1/LYST affects hematologic, immunologic and neurologic processes. Review. (PMID:18043242)
• R1836X mutation in the LYST gene is associated with Chediak Higashi syndrome. (PMID:21488161)
• gene sequencing of all exons of the lysosome trafficking regulator (CHS1/LYST) gene and revealed a nonsense mutation in exon 5 (c.925C>T, p.R309X). (PMID:24072239)
• this is the first report of a severe early-onset Chediak-Higashi syndrome (CHS0 with a homozygous LYST/CHS1 missense mutation. (PMID:24112114)
• present an AR-HSP family with cerebellar ataxia and neuropathy with a novel homozygous missense mutation in the lysosomal trafficking regulator (LYST) gene. LYST is known as the causative gene for Chediak-Higashi syndrome. (PMID:24521565)
• involved in the regulation of phospholipase D activity (PMID:24830864)
• Lysosome degradation and traffcking of cargo via autophagy, endocytosis or retrograde transport are not affected by LYST depletion. (PMID:25216107)
• Lack of LYST during endolysosomal biogenesis leads to the formation of enlarged hybrid organelles and blocks the terminal maturation of lytic granules into secretory granules. (PMID:25425525)
• Effects of LYST mutations in Chediak-Higashi syndrome show that LYST is involved in regulation of natural killer cell lytic activity, from lytic granule size to polarization and exocytosis, as well as endolysosomal compartment identity. (PMID:26478006)
• Mutation in LYST gene is associated with hemophagocytic lymphohistiocytosis. (PMID:27781387)
• Pathway analysis of the genes associated with the 46 CpG sites revealed an enrichment of immune system process genes, including LYST (cg16962115, FDR = 1.24E-04), CADM1 (cg21933078, FDR = 1.22E-02) and NFATC1 (cg06784563, FDR = 1.46E-02) (PMID:28637314)
• LYST mutations in sporadic chordoma (PMID:29026114)
• homozygous c.6077_6078insA (p.Tyr2026Terfs) mutation was detected in the LYST gene in both patients (PMID:29652989)
• LYST mutation was found in a family (PMID:31795567)
• A compound heterozygote in LYST gene, consisting of a missense mutation c.5719A > G and an intron mutation c.4863-4G > A, was identified from the patient by using amplicon sequencing. The missense mutation is reported for the first time. (PMID:31906877)
• Chediak-Higashi syndrome presenting as a hereditary spastic paraplegia. (PMID:34483340)
• LYST deficiency impairs autophagic lysosome reformation in neurons and alters lysosome number and size. (PMID:36707427)
• Spectrum of LYST mutations in Chediak-Higashi syndrome: a report of novel variants and a comprehensive review of the literature. (PMID:37788905)
• Lysosomal trafficking regulator restricts intracellular growth of Coxiella burnetii by inhibiting the expansion of Coxiella-containing vacuole and upregulating nos2 expression. (PMID:38282619)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lyst	ENSDARG00000008575
mus_musculus	Lyst	ENSMUSG00000019726
rattus_norvegicus	Lyst	ENSRNOG00000058094

Paralogs (7): NSMAF (ENSG00000035681), WDFY4 (ENSG00000128815), NBEAL1 (ENSG00000144426), NBEAL2 (ENSG00000160796), WDFY3 (ENSG00000163625), NBEA (ENSG00000172915), LRBA (ENSG00000198589)

Protein

Protein identifiers

Lysosomal-trafficking regulator — Q99698 (reviewed: Q99698)

Alternative names: Beige homolog

All UniProt accessions (15): Q99698, A0A8V8TKS8, A0A8V8TKT6, A0A8V8TKU7, A0A8V8TKW4, A0A8V8TL52, A0A8V8TL58, A0A8V8TL78, A0A8V8TL83, A0A8V8TM32, A0A8V8TM69, A0A8V8TMB4, A0A8V8TMC0, A0A8V8TME5, H7C4F5

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes. Might regulate trafficking of effectors involved in exocytosis. In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules. In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes. In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways.

Subunit / interactions. Interacts with CPAP, LIP8 and ZNF521.

Subcellular location. Cytoplasm.

Tissue specificity. Abundantly expressed in adult and fetal thymus, peripheral blood leukocytes, bone marrow and several regions of the adult brain.

Disease relevance. Chediak-Higashi syndrome (CHS) [MIM:214500] A rare autosomal recessive disorder characterized by hypopigmentation, severe immunologic deficiency, a bleeding tendency, neurologic abnormalities, abnormal intracellular transport to and from the lysosome, and giant inclusion bodies in a variety of cell types. Most patients die at an early age unless they receive an allogeneic hematopoietic stem cell transplant (SCT). The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99698-1	1	yes
Q99698-2	2
Q99698-3	3

RefSeq proteins (2): NP_000072, NP_001288294 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000409	BEACH_dom	Domain
IPR001680	WD40_rpt	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR023362	PH-BEACH_dom	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR036372	BEACH_dom_sf	Homologous_superfamily
IPR050865	BEACH_Domain	Family

Pfam: PF00400, PF02138, PF14844

UniProt features (49 total): sequence variant 15, modified residue 10, repeat 7, region of interest 4, compositionally biased region 4, splice variant 4, domain 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q99698 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 164, 165, 166, 1509, 1510, 2105, 2124, 2213, 2217, 2264

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 559 (showing top): GOBP_LYSOSOMAL_TRANSPORT, PAX4_01, GOBP_CELL_CHEMOTAXIS, GOBP_VACUOLE_ORGANIZATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_VESICLE_ORGANIZATION, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_CELLULAR_PIGMENTATION, GOBP_VACUOLAR_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY

GO Biological Process (14): phagocytosis (GO:0006909), protein transport (GO:0015031), leukocyte chemotaxis (GO:0030595), melanosome organization (GO:0032438), endosome to lysosome transport via multivesicular body sorting pathway (GO:0032510), mast cell secretory granule organization (GO:0033364), natural killer cell mediated cytotoxicity (GO:0042267), defense response to bacterium (GO:0042742), defense response to protozoan (GO:0042832), pigmentation (GO:0043473), defense response to virus (GO:0051607), lymphocyte mediated immunity (GO:0002449), immune response (GO:0006955), defense response to other organism (GO:0098542)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), microtubule cytoskeleton (GO:0015630)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	3
endocytosis	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
leukocyte migration	1
cell chemotaxis	1
pigment granule organization	1
endosome to lysosome transport	1
endosome transport via multivesicular body sorting pathway	1
secretory granule organization	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
response to bacterium	1
response to protozoan	1
defense response to other organism	1
biological_process	1
response to virus	1
leukocyte mediated immunity	1
immune system process	1
response to stimulus	1
response to other organism	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoskeleton	1

Protein interactions and networks

STRING

1444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYST	VTA1	Q9NP79	933
LYST	UNC13D	Q70J99	822
LYST	STX11	O75558	809
LYST	AP3B1	O00203	797
LYST	STXBP2	Q15833	793
LYST	RAB27A	P51159	775
LYST	HPS5	Q9UPZ3	746
LYST	HPS3	Q969F9	741
LYST	PIK3R4	Q99570	699
LYST	BLOC1S3	Q6QNY0	683
LYST	SH2D1A	O60880	680
LYST	HPS6	Q86YV9	654
LYST	FIG4	Q92562	622
LYST	BLOC1S6	Q9UL45	620
LYST	VPS4B	O75351	610

IntAct

40 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
LYST	E2	psi-mi:“MI:0915”(physical association)	0.370
Dync1li1	SSR3	psi-mi:“MI:0914”(association)	0.350
Tnpo1	CCHCR1	psi-mi:“MI:0914”(association)	0.350
LLGL2	RBBP6	psi-mi:“MI:0914”(association)	0.350
Vamp2	RTL8C	psi-mi:“MI:0914”(association)	0.350
Ccdc9	ACIN1	psi-mi:“MI:0914”(association)	0.350
SAP30	BRMS1	psi-mi:“MI:0914”(association)	0.350
TACC1	TACC2	psi-mi:“MI:0914”(association)	0.350
Cep85l	CLK2	psi-mi:“MI:0914”(association)	0.350
GAR1	TAF1	psi-mi:“MI:0914”(association)	0.350
MLH1	CAPZA2	psi-mi:“MI:0914”(association)	0.350
DAP3	MBNL1	psi-mi:“MI:0914”(association)	0.350
KIF1C	HSPA8	psi-mi:“MI:0914”(association)	0.350
KLC3	KLC1	psi-mi:“MI:0914”(association)	0.350
MYH13	C1orf226	psi-mi:“MI:0914”(association)	0.350
PPIA		psi-mi:“MI:0914”(association)	0.350
CSNK2A2	CNOT1	psi-mi:“MI:0914”(association)	0.350
CSNK2B	OSBPL8	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	PLEKHG3	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (72): LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS), LYST (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EYB2, A0JMF7, A2AHC3, A3KMW7, A5D8S0, A5WUN7, B0S6S9, D3Z8E6, D3Z987, F1M5M3, F1MJR8, F1QB81, P70347, P97412, Q0P5X5, Q0VET5, Q15468, Q2M2Z5, Q2T9I9, Q3UEN2, Q3V0M2, Q49A88, Q49AJ0, Q5CZC0, Q5RA75, Q5RHB5, Q5SW75, Q5T5Y3, Q60664, Q6JPI3, Q6NRK3, Q6PUR7, Q71F56, Q76I76, Q7M6U3, Q7TSH4, Q8C753, Q8CCC3, Q8IWB6, Q8K2J4

Diamond homologs: A0A1L8HX76, A4IHS2, A9UZS7, B3MHX6, B3NLK7, B4GIU9, B4HN85, B4J9K1, B4KQU8, B4MYI5, B4P528, O94411, P97412, P97452, Q14137, Q1DJF7, Q28XF0, Q3SZD4, Q499N3, Q4PHV3, Q4VBE8, Q54MZ3, Q54TD8, Q562C2, Q68EI0, Q7K0Y1, Q7PTC5, Q7T0W1, Q7ZXX9, Q86JF2, Q8C0J2, Q99698, Q9BV38, Q9M3B4, A8XSV3, D4A929, E7FAW3, E9Q2M9, F4HZB2, F4IG73

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
LYST	“down-regulates activity”	RAB5A	binding
LYST	“down-regulates activity”	RAB5B	binding
LYST	“down-regulates activity”	RAB5C	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	171.9×	4e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	151.7×	6e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	151.7×	6e-13
Activation of BH3-only proteins	7	112.1×	6e-12
RHO GTPases activate PKNs	7	71.6×	2e-10
Intrinsic Pathway for Apoptosis	7	66.1×	2e-10
FOXO-mediated transcription	5	54.2×	3e-07
Apoptosis	8	43.3×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	47.0×	1e-05
intracellular protein localization	7	18.8×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

3992 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	137
Likely pathogenic	107
Uncertain significance	1677
Likely benign	1654
Benign	144

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075026	NM_000081.4(LYST):c.2832del (p.Ser945fs)	Pathogenic
1075027	NM_000081.4(LYST):c.1406T>A (p.Leu469Ter)	Pathogenic
1173104	NM_000081.4(LYST):c.4322_4325del (p.Glu1441fs)	Pathogenic
1323257	NM_000081.4(LYST):c.1897A>T (p.Lys633Ter)	Pathogenic
1323258	NM_000081.4(LYST):c.11002G>T (p.Glu3668Ter)	Pathogenic
1323261	NM_000081.4(LYST):c.10468G>T (p.Gly3490Ter)	Pathogenic
1323262	NM_000081.4(LYST):c.7645C>T (p.Gln2549Ter)	Pathogenic
1323263	NM_000081.4(LYST):c.9377_9389del (p.Gly3126fs)	Pathogenic
1350886	NM_000081.4(LYST):c.575del (p.Phe191_Leu192insTer)	Pathogenic
1361717	NM_000081.4(LYST):c.236_237del (p.Leu79fs)	Pathogenic
1378721	NM_000081.4(LYST):c.6283C>T (p.Gln2095Ter)	Pathogenic
1401196	NM_000081.4(LYST):c.4978C>T (p.Gln1660Ter)	Pathogenic
1447041	NM_000081.4(LYST):c.10568_10569del (p.Val3523fs)	Pathogenic
1452670	NM_000081.4(LYST):c.8691_8692del (p.Gln2898fs)	Pathogenic
1452697	NM_000081.4(LYST):c.9449del (p.Asn3150fs)	Pathogenic
1452929	NM_000081.4(LYST):c.3574G>T (p.Glu1192Ter)	Pathogenic
1453205	NM_000081.4(LYST):c.6187del (p.Arg2063fs)	Pathogenic
1454348	NM_000081.4(LYST):c.8536-1G>A	Pathogenic
1457029	NC_000001.10:g.(?235826240)(235976381_?)del	Pathogenic
180621	NM_000081.4(LYST):c.925C>T (p.Arg309Ter)	Pathogenic
180625	NM_000081.4(LYST):c.5506C>T (p.Arg1836Ter)	Pathogenic
1926788	NM_000081.4(LYST):c.433C>T (p.Arg145Ter)	Pathogenic
2008485	NM_000081.4(LYST):c.7168C>T (p.Gln2390Ter)	Pathogenic
2012301	NM_000081.4(LYST):c.8760del (p.Ser2920fs)	Pathogenic
2020927	NM_000081.4(LYST):c.3910del (p.Glu1304fs)	Pathogenic
2022157	NM_000081.4(LYST):c.1391del (p.Glu464fs)	Pathogenic
2035081	NM_000081.4(LYST):c.4264del (p.Ala1422fs)	Pathogenic
2036761	NM_000081.4(LYST):c.6397C>T (p.Gln2133Ter)	Pathogenic
2040982	NM_000081.4(LYST):c.2540del (p.Lys847fs)	Pathogenic
2051422	NM_000081.4(LYST):c.3770T>A (p.Leu1257Ter)	Pathogenic

SpliceAI

8299 predictions. Top by Δscore:

Variant	Effect	Δscore
1:235663074:TAAGG:T	acceptor_gain	1.0000
1:235663077:GG:G	acceptor_gain	1.0000
1:235663079:C:CC	acceptor_gain	1.0000
1:235663978:TCTTA:T	donor_loss	1.0000
1:235663979:CTTA:C	donor_loss	1.0000
1:235663980:TTA:T	donor_loss	1.0000
1:235663981:TAC:T	donor_loss	1.0000
1:235663982:A:C	donor_loss	1.0000
1:235664052:TAACC:T	acceptor_loss	1.0000
1:235664053:AACC:A	acceptor_loss	1.0000
1:235664054:ACCTA:A	acceptor_loss	1.0000
1:235664055:CCTA:C	acceptor_loss	1.0000
1:235664056:C:CG	acceptor_loss	1.0000
1:235664057:T:A	acceptor_loss	1.0000
1:235700669:C:CT	acceptor_gain	1.0000
1:235702828:T:A	donor_gain	1.0000
1:235702973:TATGT:T	acceptor_gain	1.0000
1:235702974:ATGT:A	acceptor_gain	1.0000
1:235702975:TGT:T	acceptor_gain	1.0000
1:235702976:GT:G	acceptor_gain	1.0000
1:235702976:GTC:G	acceptor_loss	1.0000
1:235702977:TC:T	acceptor_loss	1.0000
1:235702978:C:CC	acceptor_gain	1.0000
1:235702978:CT:C	acceptor_loss	1.0000
1:235702979:T:G	acceptor_loss	1.0000
1:235702985:G:GC	acceptor_gain	1.0000
1:235709084:CACT:C	donor_loss	1.0000
1:235709085:ACTT:A	donor_loss	1.0000
1:235709086:CT:C	donor_loss	1.0000
1:235709087:TT:T	donor_loss	1.0000

AlphaMissense

25116 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:235664051:A:G	W3734R	1.000
1:235664051:A:T	W3734R	1.000
1:235677521:A:C	S3633R	1.000
1:235677521:A:T	S3633R	1.000
1:235677523:T:G	S3633R	1.000
1:235697242:A:G	W3469R	1.000
1:235697242:A:T	W3469R	1.000
1:235702889:G:T	P3411H	1.000
1:235702894:C:A	Q3409H	1.000
1:235702894:C:G	Q3409H	1.000
1:235702898:C:A	G3408V	1.000
1:235702898:C:T	G3408E	1.000
1:235702899:C:A	G3408W	1.000
1:235702899:C:G	G3408R	1.000
1:235702899:C:T	G3408R	1.000
1:235702902:A:C	Y3407D	1.000
1:235702902:A:G	Y3407H	1.000
1:235702910:A:T	I3404K	1.000
1:235702912:C:A	M3403I	1.000
1:235702912:C:G	M3403I	1.000
1:235702912:C:T	M3403I	1.000
1:235702913:A:C	M3403R	1.000
1:235702913:A:G	M3403T	1.000
1:235702913:A:T	M3403K	1.000
1:235702922:A:G	L3400P	1.000
1:235709097:A:C	H3379Q	1.000
1:235709097:A:T	H3379Q	1.000
1:235709099:G:C	H3379D	1.000
1:235709100:A:C	F3378L	1.000
1:235709100:A:T	F3378L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007195 (1:235727320 C>T), RS1000045292 (1:235822421 C>T), RS1000054630 (1:235784028 C>T), RS1000060111 (1:235812054 CAAGA>C), RS1000085624 (1:235688429 T>C), RS1000088535 (1:235727001 T>C), RS1000114882 (1:235873525 C>T), RS1000116396 (1:235753768 A>G), RS1000133595 (1:235681097 T>C), RS1000144494 (1:235874009 A>C,G), RS1000156000 (1:235714271 T>C), RS1000168754 (1:235753530 A>G), RS1000217475 (1:235664985 G>T), RS1000217695 (1:235769934 G>C), RS1000226378 (1:235727636 C>A)

Disease associations

OMIM: gene MIM:606897 | disease phenotypes: MIM:214500, MIM:108600, MIM:156000, MIM:202300

GenCC curated gene-disease

Disease	Classification	Inheritance
Chediak-Higashi syndrome	Definitive	Autosomal recessive
attenuated Chédiak-Higashi syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Chediak-Higashi syndrome	Definitive	AR

Mondo (8): Chediak-Higashi syndrome (MONDO:0008963), autoinflammatory syndrome (MONDO:0019751), spastic ataxia (MONDO:0017845), Meniere disease (MONDO:0007972), thrombocytopenia (MONDO:0002049), adrenocortical carcinoma, hereditary (MONDO:0008734), optic nerve disorder (MONDO:0002135), attenuated Chédiak-Higashi syndrome (MONDO:0018133)

Orphanet (5): Chédiak-Higashi syndrome (Orphanet:167), Autoinflammatory syndrome (Orphanet:93665), Spastic ataxia (Orphanet:316226), Adrenocortical carcinoma (Orphanet:1501), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

104 total (30 of 104 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000225	Gingival bleeding
HP:0000230	Gingivitis
HP:0000421	Epistaxis
HP:0000486	Strabismus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000704	Periodontitis
HP:0000707	Abnormality of the nervous system
HP:0000726	Dementia
HP:0000762	Decreased nerve conduction velocity
HP:0000763	Sensory neuropathy
HP:0000952	Jaundice
HP:0000969	Edema
HP:0000978	Bruising susceptibility
HP:0000988	Skin rash
HP:0000992	Cutaneous photosensitivity
HP:0001010	Hypopigmentation of the skin
HP:0001104	Macular hypoplasia
HP:0001107	Ocular albinism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001258	Spastic paraplegia
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003155_41	Systemic lupus erythematosus	1.000000e-09
GCST003156_1	Systemic lupus erythematosus	2.000000e-07
GCST003264_887	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST004867_16	Systemic lupus erythematosus	5.000000e-07
GCST90002380_124	Basophil percentage of white cells	1.000000e-09
GCST90002388_55	Lymphocyte count	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007992	basophil percentage of leukocytes
EFO:0004587	lymphocyte count

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D002609	Chediak-Higashi Syndrome	C11.270.040.772; C15.378.553.774.257; C16.320.798.375; C20.673.774.257; C20.673.795.375
D008575	Meniere Disease	C09.218.568.217.500
D009901	Optic Nerve Diseases	C10.292.700; C11.640
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C565972	Adrenocortical Carcinoma, Hereditary (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
trichostatin A	affects cotreatment, increases expression, affects expression	4
bisphenol A	increases methylation, increases expression, affects cotreatment	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
(+)-JQ1 compound	increases expression	2
Benzo(a)pyrene	increases methylation, decreases expression	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
vanadium pentoxide	affects expression	1
seocalcitol	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Allergens	increases expression	1

Cellosaurus cell lines

11 cell lines: 9 induced pluripotent stem cell, 1 finite cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0JX	SANi008-A	Induced pluripotent stem cell	Male
CVCL_C4NX	CIRA00150-19	Induced pluripotent stem cell	Female
CVCL_C4NY	CIRA00150-22	Induced pluripotent stem cell	Female
CVCL_C4NZ	CIRA00153-18	Induced pluripotent stem cell	Female
CVCL_C4P0	CIRA00153-9	Induced pluripotent stem cell	Female
CVCL_CW70	GM02075	Finite cell line	Female
CVCL_CW76	GM03365	Transformed cell line	Male
CVCL_ZW18	CHD-26	Induced pluripotent stem cell	Male
CVCL_ZW19	CHD-19	Induced pluripotent stem cell	Male
CVCL_ZW20	CHD-39	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

288 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE