VNN1

protein-coding

vanin 1, the group of Vanin family

Gene summary

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]

MANE transcript

NM_004666.3

Inheritance

—

ClinVar variants

U:70B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr6:132,680,849-132,714,055

External References & Databases

Ensembl (ENSG00000112299)

Transcript & Mutation Effects

hg38 • Region Span ~33.2 kb

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GenCC 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 VNN1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004666.3. 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				1 clinvar	1 clinvar	2
missense			70 clinvar	8 clinvar	5 clinvar	83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	70	9	6	85

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004666.3	RefSeq	NP_004657.2	7	MANE Select
ENST00000367928.5	Ensembl	ENSP00000356905.4	7	MANE Select
ENST00000886805.1	Ensembl	ENSP00000556864.1	7	Standard
ENST00000886805.2	Ensembl	ENSP00000556864.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pantothenate and CoA biosynthesis - Homo sapiens (human)
Pantothenate and CoA Biosynthesis
Neutrophil degranulation
Post-translational modification: synthesis of GPI-anchored proteins
Post-translational protein modification

Biological Process

acute inflammatory response
chronic inflammatory response
inflammatory response
response to oxidative stress
pantothenate metabolic process

Molecular Function

pantetheine hydrolase activity

Cellular Component

extracellular region
plasma membrane
integral component of membrane
anchored component of membrane
azurophil granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367928
Coding exons: 7
Length: 32460
Individuals with no LoFs: 125664
Homozygous LoFs: 0
Heterozygous LoFs: 82
Defined: 125746
p: 0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0677	283	280	1.01	0.0000142	3355
Missense (PolyPhen)		107	103.56	1.0332		1286
Synonymous	0.141	103	105	0.982	0.00000566	998
Loss of Function	1.44	11	17.5	0.629	7.36e-7	235

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00097	0.00090	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00017	0.00016	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.00062	0.00062	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Amidohydrolase that hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine. {ECO:0000269|PubMed:10567687, ECO:0000269|PubMed:11491533, ECO:0000269|PubMed:25478849}.;

Recessive Scores

pRec: 0.180

Intolerance Scores

LoFtool: 0.194
RVIS EVS: 1.47
RVIS percentile EVS: 95.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.780

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium