LYST

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

Basic information

Region (hg38): 1:235661040-235883724

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.

• Chédiak-Higashi syndrome (2631 variants)
• not provided (328 variants)
• Inborn genetic diseases (163 variants)
• not specified (114 variants)
• Autoinflammatory syndrome (84 variants)
• LYST-related condition (20 variants)
• Chediak-Higashi syndrome, childhood type (3 variants)
• Spastic ataxia (3 variants)
• Seizure (3 variants)
• Chediak-Higashi syndrome, adult type (2 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• Optic neuropathy (1 variants)
• Susceptibility to severe COVID-19 (1 variants)
• Abnormal bleeding;Thrombocytopenia (1 variants)
• Recurrent infections (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			21	628	13	662
missense		4	1301	25	7	1337
nonsense	40	26	2			68
start loss						0
frameshift	33	26	1			60
inframe indel		1	23			24
splice donor/acceptor (+/-2bp)	1	20	1			22
splice region			37	74	3	114
non coding			41	273	121	435
Total	74	77	1390	926	141

Highest pathogenic variant AF is 0.0000197

Variants in LYST

This is a list of pathogenic ClinVar variants found in the LYST region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-235661079-G-T		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235661109-T-G		Chédiak-Higashi syndrome	Conflicting classifications of pathogenicity (Nov 01, 2022)
1-235661148-T-C		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235661217-T-C		Chédiak-Higashi syndrome	Benign (Apr 27, 2017)
1-235661407-C-T		Chédiak-Higashi syndrome	Uncertain significance (Jan 12, 2018)
1-235661441-C-A		Chédiak-Higashi syndrome	Benign (Jan 13, 2018)
1-235661502-G-A		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235661512-A-C		Chédiak-Higashi syndrome	Uncertain significance (Jan 12, 2018)
1-235661561-C-G		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235661584-C-A		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235661645-A-G		Chédiak-Higashi syndrome	Conflicting classifications of pathogenicity (Dec 01, 2022)
1-235661665-A-G		Chédiak-Higashi syndrome	Benign (Jan 12, 2018)
1-235661729-C-T		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235661978-C-T		Chédiak-Higashi syndrome	Uncertain significance (Jan 12, 2018)
1-235662019-G-A		Chédiak-Higashi syndrome	Uncertain significance (Jan 12, 2018)
1-235662033-C-T		Chédiak-Higashi syndrome	Uncertain significance (Jan 12, 2018)
1-235662049-C-G		Chédiak-Higashi syndrome	Conflicting classifications of pathogenicity (Jan 01, 2023)
1-235662067-C-G		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235662109-T-C		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235662116-T-C		Chédiak-Higashi syndrome	Uncertain significance (Jan 12, 2018)
1-235662131-T-C		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235662215-C-T		Chédiak-Higashi syndrome	Benign (Jan 12, 2018)
1-235662228-A-G		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235662246-A-G		Chédiak-Higashi syndrome	Uncertain significance (Jan 13, 2018)
1-235662255-C-A		Chédiak-Higashi syndrome	Benign (Jan 13, 2018)

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
0.0150	0.985	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

Haploinsufficiency Scores

• pHI: 0.193
• hipred: Y
• hipred_score: 0.530
• ghis: 0.545

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

Mouse Genome Informatics

• Gene name: Lyst
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; neoplasm; pigmentation phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

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