HPS3

HPS3 biogenesis of lysosomal organelles complex 2 subunit 1, the group of Biogenesis of lysosomal organelles complex 2

Basic information

Region (hg38): 3:149129637-149173732

Links

ENSG00000163755 ∙ NCBI:84343 ∙ OMIM:606118 ∙ HGNC:15597 ∙ Uniprot:Q969F9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 3 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome without pulmonary fibrosis (Supportive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 3 (Definitive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 3	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	11455388; 20301464

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPS3 gene.

• not provided (866 variants)
• Hermansky-Pudlak syndrome 3 (230 variants)
• Hermansky-Pudlak syndrome (93 variants)
• Inborn genetic diseases (41 variants)
• Deficiency of ferroxidase (24 variants)
• not specified (21 variants)
• HPS3-related condition (3 variants)
• Hermansky-Pudlak syndrome 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPS3 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			2	310	5	317
missense		2	204	5	4	215
nonsense	23	39				62
start loss			1			1
frameshift	48	62	1			111
inframe indel			3			3
splice donor/acceptor (+/-2bp)	9	22				31
splice region			15	46	2	63
non coding			33	99	59	191
Total	80	125	244	414	68

Highest pathogenic variant AF is 0.0000526

Variants in HPS3

This is a list of pathogenic ClinVar variants found in the HPS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-149129654-T-C		Hermansky-Pudlak syndrome 3	Benign/Likely benign (Jul 09, 2018)
3-149129674-C-T		Hermansky-Pudlak syndrome 3	Uncertain significance (Jan 13, 2018)
3-149129681-C-A		Hermansky-Pudlak syndrome 3	Uncertain significance (Jan 12, 2018)
3-149129724-A-C			Uncertain significance (Feb 04, 2022)
3-149129730-C-T		Hermansky-Pudlak syndrome 3	Pathogenic (Jun 20, 2023)
3-149129733-C-T		Hermansky-Pudlak syndrome 3	Conflicting classifications of pathogenicity (Aug 16, 2022)
3-149129735-G-C			Likely benign (Apr 06, 2023)
3-149129738-C-G		Hermansky-Pudlak syndrome • Hermansky-Pudlak syndrome 3	Pathogenic (Aug 04, 2023)
3-149129741-C-T			Likely benign (Nov 09, 2021)
3-149129742-C-T			Likely benign (Dec 23, 2021)
3-149129744-G-A			Likely benign (Feb 08, 2022)
3-149129744-G-T			Likely benign (May 20, 2023)
3-149129746-AC-A			Pathogenic (Jan 10, 2020)
3-149129747-C-T			Likely benign (Dec 20, 2020)
3-149129750-G-A			Likely benign (Dec 02, 2023)
3-149129750-G-C			Likely benign (Feb 14, 2023)
3-149129753-C-T			Likely benign (Nov 24, 2022)
3-149129756-G-C			Likely benign (Mar 18, 2022)
3-149129758-C-A		Hermansky-Pudlak syndrome 3	Pathogenic/Likely pathogenic (Feb 14, 2023)
3-149129759-G-A			Likely benign (Apr 10, 2021)
3-149129761-AG-CC			Uncertain significance (Sep 17, 2021)
3-149129774-C-T		not specified • Hermansky-Pudlak syndrome 3 • Hermansky-Pudlak syndrome	Conflicting classifications of pathogenicity (Jan 31, 2024)
3-149129777-C-T			Likely benign (Jun 03, 2023)
3-149129781-C-T			Likely benign (Dec 06, 2022)
3-149129786-G-A			Likely benign (Mar 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPS3	protein_coding	protein_coding	ENST00000296051	17	44149

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.94e-21	0.0999	125593	0	155	125748	0.000616

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.160	525	535	0.981	0.0000277	6529
Missense in Polyphen		263	276.53	0.95107		3491
Synonymous	-0.378	215	208	1.03	0.0000110	1927
Loss of Function	1.44	38	48.9	0.778	0.00000239	641

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000763	0.000761
Ashkenazi Jewish	0.00179	0.00179
East Asian	0.00158	0.00158
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000505	0.000501
Middle Eastern	0.00158	0.00158
South Asian	0.00102	0.00101
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in early stages of melanosome biogenesis and maturation. {ECO:0000250|UniProtKB:Q91VB4}.

Recessive Scores

• pRec: 0.164

Intolerance Scores

• loftool: 0.961
• rvis_EVS: -1.28
• rvis_percentile_EVS: 5.13

Haploinsufficiency Scores

• pHI: 0.551
• hipred: N
• hipred_score: 0.251
• ghis: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.128

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hps3
• 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); homeostasis/metabolism phenotype; pigmentation phenotype; hematopoietic system phenotype; vision/eye phenotype

Gene ontology

• Biological process: organelle organization;pigmentation
• Cellular component: cytoplasm;BLOC-2 complex
• Molecular function: protein binding