HPS1

HPS1 biogenesis of lysosomal organelles complex 3 subunit 1, the group of MicroRNA protein coding host genes|Biogenesis of lysosomal organelles complex 3

Basic information

Region (hg38): 10:98410938-98446963

Previous symbols: [ "HPS" ]

Links

ENSG00000107521 ∙ NCBI:3257 ∙ OMIM:604982 ∙ HGNC:5163 ∙ Uniprot:Q92902 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 1 (Definitive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 1 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome with pulmonary fibrosis (Supportive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 1	AR	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic; Pulmonary	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; Lung transplantation has been described	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary	3921802; 2916560; 8896559; 9562579; 9497254; 10411151; 10768343; 11414528; 12126938; 16210149; 19398212; 19729668; 20301464; 20514622; 20662851; 21833017

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPS1 gene.

• not provided (799 variants)
• Hermansky-Pudlak syndrome 1 (246 variants)
• Hermansky-Pudlak syndrome (118 variants)
• not specified (49 variants)
• Inborn genetic diseases (27 variants)
• HPS1-related condition (7 variants)
• Hermansky-Pudlak syndrome with pulmonary fibrosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPS1 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			3	263	7	273
missense	2	5	204	14	4	229
nonsense	20	15				35
start loss						0
frameshift	31	33				64
inframe indel			2			2
splice donor/acceptor (+/-2bp)		21				21
splice region	1	2	7	51	4	65
non coding		1	31	102	56	190
Total	53	75	240	379	67

Highest pathogenic variant AF is 0.000361

Variants in HPS1

This is a list of pathogenic ClinVar variants found in the HPS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-98410950-C-T		not specified	Uncertain significance (Mar 23, 2023)
10-98415012-C-G		not specified	Uncertain significance (Sep 20, 2023)
10-98415024-C-T		not specified	Uncertain significance (Feb 23, 2023)
10-98415071-C-T		not specified	Uncertain significance (Jan 19, 2024)
10-98415122-C-G		not specified	Uncertain significance (Feb 17, 2023)
10-98416238-G-T		Hermansky-Pudlak syndrome 1	Benign (Jan 13, 2018)
10-98416315-C-T		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 13, 2018)
10-98416329-C-T		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 13, 2018)
10-98416347-A-G		Hermansky-Pudlak syndrome 1	Benign (Jan 12, 2018)
10-98416347-AGG-GGA		Hermansky-Pudlak syndrome	Uncertain significance (Jun 14, 2016)
10-98416349-G-A		Hermansky-Pudlak syndrome 1	Benign (Jan 13, 2018)
10-98416352-A-T		Hermansky-Pudlak syndrome 1	Uncertain significance (Apr 27, 2017)
10-98416397-C-T		Hermansky-Pudlak syndrome 1	Benign (Jan 13, 2018)
10-98416479-C-T		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 12, 2018)
10-98416521-G-A		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 12, 2018)
10-98416559-T-C		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 12, 2018)
10-98416563-C-A		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 12, 2018)
10-98416582-A-G		Hermansky-Pudlak syndrome 1	Benign (Jan 13, 2018)
10-98416596-C-T		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 13, 2018)
10-98416609-T-C		Hermansky-Pudlak syndrome 1	Benign (Jan 13, 2018)
10-98416612-A-C		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 12, 2018)
10-98416621-G-A		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 13, 2018)
10-98416648-C-T		Hermansky-Pudlak syndrome 1	Benign (Jan 12, 2018)
10-98416796-T-C		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 13, 2018)
10-98416798-C-A		Hermansky-Pudlak syndrome 1	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPS1	protein_coding	protein_coding	ENST00000325103	18	30730

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.32e-7	1.00	125671	0	77	125748	0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.116	401	408	0.984	0.0000265	4511
Missense in Polyphen		151	151.46	0.99696		1765
Synonymous	-0.604	191	181	1.06	0.0000120	1425
Loss of Function	3.07	18	38.6	0.467	0.00000193	422

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000619	0.000618
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000389	0.000378
Middle Eastern	0.000165	0.000163
South Asian	0.000330	0.000327
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38 (PubMed:23084991). {ECO:0000269|PubMed:23084991}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.813
• rvis_EVS: 0.85
• rvis_percentile_EVS: 88.49

Haploinsufficiency Scores

• pHI: 0.566
• hipred: N
• hipred_score: 0.289
• ghis: 0.461

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.637

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hps1
• Phenotype: cellular 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; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; pigmentation 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; 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); respiratory system phenotype

Gene ontology

• Biological process: lysosome organization;visual perception;response to stimulus;melanosome assembly
• Cellular component: cytoplasm;lysosome;cytosol;BLOC-3 complex;cytoplasmic vesicle
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;protein dimerization activity