VPS45

vacuolar protein sorting 45 homolog

Basic information

Region (hg38): 1:150067279-150145329

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 (583 variants)
Inborn_genetic_diseases (50 variants)
not_provided (41 variants)
not_specified (26 variants)
VPS45-related_disorder (10 variants)
Severe_congenital_neutropenia (1 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. These statistics are base on transcript: NM_000007259.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	233 clinvar	3 clinvar	245
missense	1 clinvar	4 clinvar	178 clinvar	5 clinvar	1 clinvar	189
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift		2 clinvar	3 clinvar	1 clinvar		6
splice donor/acceptor (+/-2bp)					1 clinvar	1
Total	1	7	192	239	5

Highest pathogenic variant AF is 0.0000116293

Loading clinvar variants...

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
Phenotype

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