VPS45

Chr 1

vacuolar protein sorting 45 homolog

Also known as: H1, H1VPS45, SCN5, VPS45A, VPS45B, VPS54A, VSP45, VSP45A

NCBI Gene: 11311 ENSG00000136631 UniProt: Q9NRW7

Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec1 domain family, and shows a high degree of sequence similarity to mouse, rat and yeast Vps45. The exact function of this gene is not known, but its high expression in peripheral blood mononuclear cells suggests a role in trafficking proteins, including inflammatory mediators. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]

Research

ResearchGenerating clinical summary…

LOEUF 0.66

Clinical Summary— VPS45

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 205 VUS of 699 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.000

Z-score 3.14

OE 0.43 (0.28–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.63Z-score

OE missense 0.74 (0.66–0.83)

229 obs / 309.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.43 (0.28–0.66)

0≤0.351.4

Missense OE?0.74 (0.66–0.83)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 15 / 35.1Missense obs/exp: 229 / 309.5Syn Z: 1.67

ClinVar Variant Classifications

699 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic15

VUS205

Likely Benign409

Benign37

Conflicting14

Pathogenic

Likely Pathogenic

205

VUS

409

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	13	2	0	0	15
VUS	1	185	11	8	205
Likely Benign	3	13	168	225	409
Benign	1	0	34	2	37
Conflicting	—				14
Total	18	201	213	235	681

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap VPS45 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →