VNN1

Chr 6

vanin 1

Also known as: HDLCQ8, Tiff66

NCBI Gene: 8876ENSG00000112299UniProt: O95497

This gene encodes a member of the vanin family of proteins, which 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. This protein, like its mouse homolog, is likely a GPI-anchored cell surface molecule. The mouse protein is expressed by the perivascular thymic stromal cells and regulates migration of T-cell progenitors to the thymus. This gene lies in close proximity to, and in the same transcriptional orientation as, two other vanin genes on chromosome 6q23-q24. [provided by RefSeq, Feb 2009]

105
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— VNN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 76 VUS of 105 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

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.
1.04LOEUF
pLI 0.000
Z-score 1.44
OE 0.63 (0.40–1.04)
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.
-0.07Z-score
OE missense 1.01 (0.92–1.12)
283 obs / 279.8 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.0.63 (0.40–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.12)
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.0.98
0≤1.21.6
LoF obs/exp: 11 / 17.5Missense obs/exp: 283 / 279.8Syn Z: 0.14

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS76
Likely Benign9
Benign9
11
Pathogenic
76
VUS
9
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
70
6
0
76
Likely Benign
0
8
0
1
9
Benign
1
5
2
1
9
Total183192105

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

View in ClinVar →

Protein Context — Lollipop Plot

VNN1 · 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 1; VNN1
MIM #603570 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Harnessing the Vnn1 pantetheinase pathway boosts short chain fatty acids production and mucosal protection in colitis.
Millet V et al.·Gut
2023
Revealing VNN1: An Emerging and Promising Target for Inflammation and Redox Balance.
Lv L et al.·Immun Inflamm Dis
2025
Exploring the shared pathogenic mechanisms of tuberculosis and COVID-19: emphasizing the role of VNN1 in severe COVID-19.
Sun P et al.·Front Cell Infect Microbiol
2024Functional
SEMA3C regulates tumor-associated macrophage phenotype and influences lung cancer cell migration and invasion through VNN1.
Liu R et al.·Hum Exp Toxicol
2025
Omics data integration analysis identified new biological insights into chronic antibody-mediated rejection (CAMR).
Bruschi M et al.·J Transl Med
2025
Potential New Expression Biomarkers for Anorexia Nervosa.
Verebi C et al.·Am J Med Genet B Neuropsychiatr Genet
2025
Upregulated Vanins and their potential contribution to periodontitis.
Yu W et al.·BMC Oral Health
2022
Differential transcriptomic host responses in the early phase of viral and bacterial infections in human lung tissue explants ex vivo.
Sohail A et al.·Respir Res
2024
Vanin-1 is a key activator for hepatic gluconeogenesis.
Chen S et al.·Diabetes
2014
VNN1, a potential biomarker for pancreatic cancer-associated new-onset diabetes, aggravates paraneoplastic islet dysfunction by increasing oxidative stress.
Kang M et al.·Cancer Lett
2016
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
Single Cell Sequencing TechnologyGene Expression ProfilingGene Expression

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.

NOT YET RECRUITING
NCT06846645Chinese University of Hong KongStarted 2025-02
No intervention
Gene ExpressionGene Expression ProfilingInfection

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA

ACTIVE NOT RECRUITING
NCT06838780Chinese University of Hong KongStarted 2018-01-01
No intervention

External Resources

Links to major genomics databases and tools