VPS39

Chr 15

VPS39 subunit of HOPS complex

Also known as: TLP, VAM6, hVam6p

NCBI Gene: 23339 ENSG00000166887 UniProt: Q96JC1

This gene encodes a protein that may promote clustering and fusion of late endosomes and lysosomes. The protein may also act as an adaptor protein that modulates the transforming growth factor-beta response by coupling the transforming growth factor-beta receptor complex to the Smad pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

Mechanism· predicted

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?

0.68LOEUF

pLI 0.000

Z-score 3.45

OE 0.50 (0.36–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.65Z-score

OE missense 0.66 (0.60–0.72)

314 obs / 476.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.50 (0.36–0.68)

0≤0.351.4

Missense OE?0.66 (0.60–0.72)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 27 / 54.4Missense obs/exp: 314 / 476.8Syn Z: 0.01

Background carrier burden — how many people carry a rare variant somewhere in VPS39?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

889 rare PASS variants

Rare truncating (LoF)

1 in 1,600

144 rare PASS variants

Rare synonymous (reference)

1 in 90

413 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for VPS39. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,600
South Asian	~43k	1 in 64	1 in 2,500
Remaining (unassigned)	~30k	1 in 90	1 in 2,700
European (Finnish)	~27k	1 in 370	1 in 1,500
Admixed American	~22k	1 in 100	1 in 1,400
African / African American	~21k	1 in 81	1 in 1,200
East Asian	~20k	1 in 76	1 in 1,600
Ashkenazi Jewish	~13k	1 in 420	1 in 2,200
Middle Eastern	~2,884	1 in 88	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 25 coding exons well covered in gnomAD exomes and genomes.? see exons ↓