LYST

lysosomal trafficking regulator, the group of WD repeat domain containing|BEACH domain containing |MicroRNA protein coding host genes

Basic information

Region (hg38): 1:235661041-235883724

Previous symbols: [ "CHS1" ]

Links

ENSG00000143669 ∙ NCBI:1130 ∙ OMIM:606897 ∙ HGNC:1968 ∙ Uniprot:Q99698 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Chediak-Higashi syndrome (Definitive), mode of inheritance: AR
• Chediak-Higashi syndrome (Strong), mode of inheritance: AR
• Chediak-Higashi syndrome (Strong), mode of inheritance: AR
• Chediak-Higashi syndrome (Supportive), mode of inheritance: AR
• attenuated Chédiak-Higashi syndrome (Supportive), mode of inheritance: AR
• Chediak-Higashi syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chediak-Higashi syndrome	AR	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals can have infection susceptibility, and prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for hematologic complications and malignancy is warranted; For the accelerated phase, chemoimmunotherapy then transition to continuation therapy can be beneficial; For bleeding, platelet transfusions and DDAVP may be beneficial to prevent and/or treat episodes; BMT/HSCT has been described	Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic	13584476; 5908967; 5156632; 5064229; 711501; 2697195; 2070553; 2058369; 8030398; 8701696; 9215680; 10422800; 10527680; 11857544; 15790783; 20503323; 20301751; 21488161; 23521865; 24521565

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LYST gene.

• Ch�diak-Higashi_syndrome (3484 variants)
• Inborn_genetic_diseases (454 variants)
• not_provided (452 variants)
• not_specified (194 variants)
• LYST-related_disorder (96 variants)
• Autoinflammatory_syndrome (81 variants)
• CHEDIAK-HIGASHI_SYNDROME,_CHILDHOOD_TYPE (7 variants)
• Meniere_disease (6 variants)
• Thrombocytopenia (3 variants)
• Abnormal_bleeding (3 variants)
• CHEDIAK-HIGASHI_SYNDROME,_ADULT_TYPE (3 variants)
• Spastic_ataxia (3 variants)
• Recurrent_infections (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Adrenocortical_carcinoma,_hereditary (1 variants)
• Susceptibility_to_severe_COVID-19 (1 variants)
• Optic_neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LYST gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000081.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			21	1133	9	1163
missense	2	10	1580	77	11	1680
nonsense	64	45	8			117
start loss						0
frameshift	67	48	13			128
splice donor/acceptor (+/-2bp)	4	37	8			49
Total	137	140	1630	1210	20

Highest pathogenic variant AF is 0.000026757334

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LYST	protein_coding	protein_coding	ENST00000389794	51	222600

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125658	0	90	125748	0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	1758	1.93e+3	0.910	0.000101	25039
Missense in Polyphen		592	754.77	0.78434		9855
Synonymous	-0.232	706	698	1.01	0.0000375	7172
Loss of Function	9.58	44	184	0.239	0.0000104	2282

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000998	0.000934
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000329	0.000326
Finnish	0.000555	0.000554
European (Non-Finnish)	0.000344	0.000325
Middle Eastern	0.000329	0.000326
South Asian	0.000294	0.000294
Other	0.000655	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be required for sorting endosomal resident proteins into late multivesicular endosomes by a mechanism involving microtubules.

Intolerance Scores

• loftool: 0.601
• rvis_EVS: -3.04
• rvis_percentile_EVS: 0.5

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.498

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: lyst
• Affected structure: liver
• Phenotype tag: abnormal
• Phenotype quality: fatty

Gene ontology

• Biological process: lysosome organization;protein transport;leukocyte chemotaxis;melanosome organization;endosome to lysosome transport via multivesicular body sorting pathway;mast cell secretory granule organization;natural killer cell mediated cytotoxicity;defense response to bacterium;defense response to protozoan;pigmentation;defense response to virus
• Cellular component: cytoplasm;microtubule cytoskeleton
• Molecular function: protein binding