HPS6

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

Basic information

Region (hg38): 10:102065349-102068036

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 (Definitive), mode of inheritance: AR
• 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

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 (477 variants)
• Inborn_genetic_diseases (124 variants)
• Hermansky-Pudlak_syndrome_6 (110 variants)
• not_specified (51 variants)
• HPS6-related_disorder (24 variants)
• Hermansky-Pudlak_syndrome (21 variants)
• Storage_pool_disease_of_platelets (2 variants)
• Thrombocytopenia (1 variants)
• 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. These statistics are base on transcript: NM_000024747.6. 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			13	182	3	198
missense	1	5	272	23		301
nonsense	25	11				36
start loss		1	1			2
frameshift	37	24	3			64
splice donor/acceptor (+/-2bp)						0
Total	63	41	289	205	3

Highest pathogenic variant AF is 0.00008951629

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	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

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

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