HPS6

HPS6 biogenesis of lysosomal organelles complex 2 subunit 3, the group of Biogenesis of lysosomal organelles complex 2

Basic information

Region (hg38): 10:102065348-102068036

Links

ENSG00000166189 ∙ NCBI:79803 ∙ OMIM:607522 ∙ HGNC:18817 ∙ Uniprot:Q86YV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 6 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome without pulmonary fibrosis (Supportive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 6 (Definitive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 6 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 6	AR	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic	Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary	12548288; 20301464; 27225848

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPS6 gene.

• not provided (325 variants)
• Hermansky-Pudlak syndrome 6 (81 variants)
• Inborn genetic diseases (39 variants)
• not specified (34 variants)
• Hermansky-Pudlak syndrome (18 variants)
• HPS6-related condition (6 variants)
• Storage pool disease of platelets (2 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPS6 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			11	87	7	105
missense	1	2	199	6	1	209
nonsense	13	7				20
start loss			1			1
frameshift	15	11	2			28
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1		1	2
Total	29	20	218	93	9

Highest pathogenic variant AF is 0.0000525

Variants in HPS6

This is a list of pathogenic ClinVar variants found in the HPS6 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-102065470-G-A		Hermansky-Pudlak syndrome 6 • not specified • HPS6-related disorder	Conflicting classifications of pathogenicity (Jun 10, 2020)
10-102065475-A-G		Hermansky-Pudlak syndrome 6	Uncertain significance (Apr 01, 2022)
10-102065478-A-T			Pathogenic (Jun 09, 2023)
10-102065481-C-T		Hermansky-Pudlak syndrome 6	Uncertain significance (Aug 23, 2022)
10-102065485-C-T		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
10-102065487-G-A			Uncertain significance (Jul 29, 2022)
10-102065489-G-A			Likely benign (Sep 21, 2023)
10-102065490-ACT-A		Hermansky-Pudlak syndrome 6	Likely pathogenic (Dec 30, 2017)
10-102065491-C-T			Uncertain significance (Aug 01, 2022)
10-102065498-G-T			Likely benign (May 19, 2023)
10-102065500-TG-T			Pathogenic (Nov 05, 2023)
10-102065504-C-G		HPS6-related disorder	Likely benign (Jan 11, 2024)
10-102065504-C-T			Likely benign (Apr 14, 2023)
10-102065507-G-A			Likely benign (Mar 27, 2023)
10-102065511-CT-GG			Uncertain significance (Oct 24, 2022)
10-102065516-C-T			Likely benign (Jan 03, 2024)
10-102065517-G-A			Uncertain significance (May 06, 2021)
10-102065518-C-G		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
10-102065519-C-T			Likely benign (Aug 02, 2023)
10-102065521-T-C			Uncertain significance (Jan 15, 2022)
10-102065523-G-GGCGGC		Hermansky-Pudlak syndrome • HPS6-related disorder	Pathogenic (Dec 24, 2023)
10-102065528-C-T			Likely benign (Nov 19, 2023)
10-102065531-G-A			Likely benign (Dec 09, 2023)
10-102065544-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
10-102065552-G-T			Likely benign (Nov 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPS6	protein_coding	protein_coding	ENST00000299238	1	2646

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000277	0.997	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0257	404	403	1.00	0.0000235	4748
Missense in Polyphen		108	127.6	0.84639		1637
Synonymous	-1.65	220	191	1.15	0.0000103	1880
Loss of Function	2.61	10	23.7	0.421	0.00000160	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules (PubMed:17041891). Acts as cargo adapter for the dynein-dynactin motor complex to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Facilitates retrograde lysosomal trafficking by linking the motor complex to lysosomes, and perinuclear positioning of lysosomes is crucial for the delivery of endocytic cargos to lysosomes, for lysosome maturation and functioning (PubMed:25189619). {ECO:0000269|PubMed:17041891, ECO:0000269|PubMed:25189619}.

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.341
• rvis_EVS: -1.04
• rvis_percentile_EVS: 7.71

Haploinsufficiency Scores

• pHI: 0.101
• hipred: Y
• hipred_score: 0.520
• ghis: 0.644

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.861

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hps6
• Phenotype: immune system phenotype; renal/urinary system 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); vision/eye phenotype; normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; pigmentation phenotype; homeostasis/metabolism phenotype; craniofacial 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

Gene ontology

• Biological process: organelle organization;blood coagulation;melanocyte differentiation;lysosome localization;protein localization to membrane
• Cellular component: lysosomal membrane;endoplasmic reticulum;membrane;BLOC-2 complex;early endosome membrane
• Molecular function: protein binding;Rab GTPase binding;GTP-dependent protein binding