VPS45

vacuolar protein sorting 45 homolog

Basic information

Region (hg38): 1:150067278-150145329

Previous symbols: [ "VPS45B", "VPS45A" ]

Links

ENSG00000136631 ∙ NCBI:11311 ∙ OMIM:610035 ∙ HGNC:14579 ∙ Uniprot:Q9NRW7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital neutropenia-myelofibrosis-nephromegaly syndrome (Supportive), mode of inheritance: AR
• congenital neutropenia-myelofibrosis-nephromegaly syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neutropenia, severe congenital, 5, autosomal recessive	AR	Allergy/Immunology/Infectious	Individuals have been described with frequent and severe infections, and awareness may allow prophylactic measures (including treatment with G-CSF), as well as early and aggressive treatment of infections; HSCT has been described	Allergy/Immunology/Infectious	23599270; 23738510

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS45 gene.

• Congenital neutropenia-myelofibrosis-nephromegaly syndrome (430 variants)
• not provided (41 variants)
• not specified (25 variants)
• Inborn genetic diseases (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS45 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	180	3	185
missense	1	2	125	2	1	131
nonsense			2			2
start loss						0
frameshift			3	1		4
inframe indel						0
splice donor/acceptor (+/-2bp)					1	1
splice region			5	37	1	43
non coding			3	65	28	96
Total	1	2	135	248	33

Highest pathogenic variant AF is 0.00000659

Variants in VPS45

This is a list of pathogenic ClinVar variants found in the VPS45 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-150067346-T-A			Benign (May 17, 2021)
1-150067854-C-T		Congenital neutropenia-myelofibrosis-nephromegaly syndrome • not specified • VPS45-related disorder	Conflicting classifications of pathogenicity (Mar 16, 2020)
1-150067855-G-T			Uncertain significance (Feb 01, 2024)
1-150067863-C-T		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Jun 29, 2023)
1-150067884-G-A		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Apr 14, 2023)
1-150067890-T-C		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Nov 27, 2023)
1-150067895-A-G		Congenital neutropenia-myelofibrosis-nephromegaly syndrome • Inborn genetic diseases	Uncertain significance (Dec 31, 2023)
1-150067905-G-A		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Jun 20, 2023)
1-150067914-G-A		Congenital neutropenia-myelofibrosis-nephromegaly syndrome • VPS45-related disorder	Likely benign (Jun 27, 2022)
1-150067915-C-T		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Uncertain significance (Jul 19, 2022)
1-150067919-G-A			Uncertain significance (Mar 30, 2021)
1-150067921-A-G		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Uncertain significance (Sep 07, 2021)
1-150067929-A-G		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Nov 06, 2023)
1-150067930-C-A		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Uncertain significance (May 29, 2022)
1-150067935-C-T		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Mar 10, 2022)
1-150067944-A-G		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Jan 31, 2024)
1-150067950-G-A		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Uncertain significance (Jul 19, 2022)
1-150067960-C-G		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Jun 27, 2023)
1-150067960-C-CTT		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Dec 11, 2022)
1-150067964-T-C		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Jul 29, 2022)
1-150067966-C-T		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Dec 19, 2022)
1-150067967-T-G		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Jul 06, 2023)
1-150067968-C-A		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Oct 14, 2023)
1-150067969-A-T		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Jul 06, 2022)
1-150068612-A-T		Congenital neutropenia-myelofibrosis-nephromegaly syndrome	Likely benign (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS45	protein_coding	protein_coding	ENST00000369130	15	78137

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000509	1.00	125705	0	42	125747	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.63	229	309	0.740	0.0000161	3731
Missense in Polyphen		65	112.74	0.57652		1371
Synonymous	1.67	85	107	0.795	0.00000513	1095
Loss of Function	3.14	15	35.1	0.427	0.00000208	394

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000207	0.000207
Ashkenazi Jewish	0.00	0.00
East Asian	0.000282	0.000272
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000162	0.000158
Middle Eastern	0.000282	0.000272
South Asian	0.000328	0.000327
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in vesicle-mediated protein trafficking from the Golgi stack through the trans-Golgi network.
• Pathway: Endocytosis - Homo sapiens (human);Vesicle-mediated transport;Membrane Trafficking;Factors involved in megakaryocyte development and platelet production;Hemostasis;Intra-Golgi traffic;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.830
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.153
• hipred: Y
• hipred_score: 0.648
• ghis: 0.618

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.829

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps45

Zebrafish Information Network

• Gene name: vps45
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: intracellular protein transport;vesicle docking involved in exocytosis;blood coagulation
• Cellular component: Golgi membrane;cellular_component;Golgi apparatus;synaptic vesicle;endosome membrane;integral component of membrane
• Molecular function: molecular_function;protein binding