VNN2
protein-codingvanin 2, the group of Vanin family
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VNN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004665.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 89 | 7 | 3 | 99 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 93 | 7 | 3 | 103 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004656.3 | 7 | MANE Select | |
| Ensembl | ENSP00000322276.6 | 7 | MANE Select | |
| RefSeq | NP_001229279.2 | 5 | Standard | |
| RefSeq | NP_511043.2 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pantothenate and CoA biosynthesis - Homo sapiens (human)
- Post-translational modification: synthesis of GPI-anchored proteins
- Post-translational protein modification
- Metabolism of proteins
- Metabolism
Biological Process
- pantothenate metabolic process
Molecular Function
- pantetheine hydrolase activity
Cellular Component
- extracellular region
- plasma membrane
- anchored component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326499
- Coding exons
- 7
- Length
- 19590
- Individuals with no LoFs
- 125583
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 162
- Defined
- 125745
- p
- 0.000644
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.467 | 299 | 277 | 1.08 | 0.0000134 | 3391 |
| Missense (PolyPhen) | 86 | 85.633 | 1.0043 | 1106 | ||
| Synonymous | -0.469 | 111 | 105 | 1.06 | 0.00000549 | 1031 |
| Loss of Function | -0.374 | 21 | 19.2 | 1.09 | 9.64e-7 | 233 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00069 | 0.00068 | rare |
| Latino/Admixed American | 0.00045 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0015 | 0.0015 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00072 | 0.00072 | rare |
| South Asian | 0.00081 | 0.00072 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Amidohydrolase that hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine. Involved in the thymus homing of bone marrow cells. May regulate beta-2 integrin-mediated cell adhesion, migration and motility of neutrophil. {ECO:0000269|PubMed:11491533}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- RVIS EVS
- 1.33
- RVIS percentile EVS
- 94.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.900
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |