VNN2

Chr 6

vanin 2

Also known as: FOAP-4, GPI-80

NCBI Gene: 8875ENSG00000112303UniProt: O95498

This gene product is a member of the Vanin family of proteins that share extensive sequence similarity with each other, and also with biotinidase. The family includes secreted and membrane-associated proteins, a few of which have been reported to participate in hematopoietic cell trafficking. No biotinidase activity has been demonstrated for any of the vanin proteins, however, they possess pantetheinase activity, which may play a role in oxidative-stress response. The encoded protein is a GPI-anchored cell surface molecule that plays a role in transendothelial migration of neutrophils. This gene lies in close proximity to, and in same transcriptional orientation as two other vanin genes on chromosome 6q23-q24. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

112
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— VNN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 91 VUS of 112 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.57LOEUF
pLI 0.000
Z-score -0.37
OE 1.09 (0.77–1.57)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.47Z-score
OE missense 1.08 (0.98–1.19)
299 obs / 277.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.09 (0.77–1.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.98–1.19)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 21 / 19.2Missense obs/exp: 299 / 277.1Syn Z: -0.47

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS91
Likely Benign5
Benign3
Conflicting1
12
Pathogenic
91
VUS
5
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
85
6
0
91
Likely Benign
0
5
0
0
5
Benign
0
3
0
0
3
Conflicting
—1
Total093180112

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

View in ClinVar →

Protein Context — Lollipop Plot

VNN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
VANIN 2; VNN2
MIM #603571 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
VNN2-expressing circulating monocytes exhibit unique functional characteristics and are decreased in patients with primary Sjögren's syndrome.
Bahabayi A et al.·J Autoimmun
2024Cohort
Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.
Zhu R et al.·Cell Res
2021Cohort
Healthy myeloid-derived suppressor cells express the surface ectoenzyme Vanin-2 (VNN2).
Soler DC et al.·Mol Immunol
2022
Upregulated Vanins and their potential contribution to periodontitis.
Yu W et al.·BMC Oral Health
2022
Rare Variant Association Analysis Uncovers Involvement of VNN2 in Stroke Outcome.
Alcaide-Consuegra E et al.·Stroke
2025
The hematopoietic stem cell marker VNN2 is associated with chemoresistance in pediatric B-cell precursor ALL.
Bornhauser B et al.·Blood Adv
2020
The proteomic signature of circulating extracellular vesicles following intracerebral hemorrhage: Novel insights into mechanisms underlying recovery.
Casado-Fernández L et al.·Neurobiol Dis
2024Functional
Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia.
Louka E et al.·J Exp Med
2021
Comparative transcriptome analysis of unfractionated peripheral blood leukocytes after exercise in human.
Nie M et al.·Sci Rep
2023
Pan-cancer single-cell and spatial transcriptomics implicate cancer-associated fibroblasts in neutrophil immunosuppressive phenotypic transitions and immunotherapy resistance.
Guo Z et al.·Funct Integr Genomics
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools