HPS5

HPS5 biogenesis of lysosomal organelles complex 2 subunit 2, the group of Biogenesis of lysosomal organelles complex 2 |WD repeat domain containing

Basic information

Region (hg38): 11:18278667-18322198

Links

ENSG00000110756 ∙ NCBI:11234 ∙ OMIM:607521 ∙ HGNC:17022 ∙ Uniprot:Q9UPZ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 5 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome without pulmonary fibrosis (Supportive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 5 (Definitive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 5 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 5	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; 21833017

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPS5 gene.

• not provided (616 variants)
• Hermansky-Pudlak syndrome 5 (123 variants)
• not specified (47 variants)
• Inborn genetic diseases (40 variants)
• Hermansky-Pudlak syndrome (12 variants)
• HPS5-related condition (4 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 HPS5 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			6	122	5	133
missense		1	239	8	2	250
nonsense	17	1				18
start loss				1		1
frameshift	17	2				19
inframe indel			4			4
splice donor/acceptor (+/-2bp)	4	12	1			17
splice region		1	11	17	1	30
non coding	1		37	90	85	213
Total	39	16	287	221	92

Highest pathogenic variant AF is 0.0000263

Variants in HPS5

This is a list of pathogenic ClinVar variants found in the HPS5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-18278681-T-C		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 13, 2018)
11-18278814-A-T		Hermansky-Pudlak syndrome 5	Benign (Jan 12, 2018)
11-18278859-A-C		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 13, 2018)
11-18278877-CTT-C		Hermansky-Pudlak syndrome	Uncertain significance (Jun 14, 2016)
11-18278922-A-T		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 13, 2018)
11-18278926-A-C		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 12, 2018)
11-18279043-A-G		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 13, 2018)
11-18279070-T-G		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 12, 2018)
11-18279078-G-A		Hermansky-Pudlak syndrome 5	Benign (Jan 13, 2018)
11-18279180-T-A		Hermansky-Pudlak syndrome 5	Benign (Jan 12, 2018)
11-18279194-T-C		Hermansky-Pudlak syndrome 5	Likely benign (Jan 13, 2018)
11-18279227-T-G		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 12, 2018)
11-18279407-G-A		Hermansky-Pudlak syndrome 5	Benign (Jan 12, 2018)
11-18279413-T-C		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 12, 2018)
11-18279418-G-T		Hermansky-Pudlak syndrome 5	Benign (Jan 13, 2018)
11-18279439-A-T		Hermansky-Pudlak syndrome 5	Benign (Jan 13, 2018)
11-18279520-C-T		Hermansky-Pudlak syndrome 5	Likely benign (Jan 12, 2018)
11-18279582-A-G		Hermansky-Pudlak syndrome 5	Benign (Nov 12, 2018)
11-18279583-G-A		Hermansky-Pudlak syndrome 5	Benign (Nov 12, 2018)
11-18279606-A-C		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 12, 2018)
11-18279700-G-A		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 13, 2018)
11-18279725-C-T		Hermansky-Pudlak syndrome 5	Uncertain significance (Mar 30, 2018)
11-18279787-G-T		Hermansky-Pudlak syndrome 5	Uncertain significance (Jan 13, 2018)
11-18279812-G-A		Hermansky-Pudlak syndrome 5	Likely benign (Jan 13, 2018)
11-18279877-T-C		not specified	Likely benign (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPS5	protein_coding	protein_coding	ENST00000349215	22	43523

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.90e-13	0.999	125627	0	121	125748	0.000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0640	585	589	0.993	0.0000297	7397
Missense in Polyphen		197	230.94	0.85302		2959
Synonymous	0.349	209	216	0.970	0.0000110	2157
Loss of Function	3.17	30	55.5	0.540	0.00000258	729

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000984	0.000984
Ashkenazi Jewish	0.00179	0.00179
East Asian	0.000653	0.000653
Finnish	0.000556	0.000554
European (Non-Finnish)	0.000371	0.000369
Middle Eastern	0.000653	0.000653
South Asian	0.000359	0.000359
Other	0.000163	0.000163

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. Regulates intracellular vesicular trafficking in fibroblasts. May be involved in the regulation of general functions of integrins. {ECO:0000269|PubMed:15296495, ECO:0000269|PubMed:17301833}.

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.963
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.27

Haploinsufficiency Scores

• pHI: 0.111
• hipred: N
• hipred_score: 0.448
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.837

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hps5
• 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; immune system phenotype; renal/urinary system phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; 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); pigmentation phenotype

Zebrafish Information Network

• Gene name: hps5
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

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