NAV3

protein-coding

neuron navigator 3

Gene summary

This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. Multiple alternatively spliced transcript variants for this gene have been described but only one has had its full-length nature determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001024383.2

Inheritance

AR, AD

ClinVar variants

P:4U:336B:17

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr12:77,324,641-78,213,010

External References & Databases

Ensembl (ENSG00000067798)

Transcript & Mutation Effects

hg38 • Region Span ~888.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NAV3 variants in ClinVar

12 Conditions Cataloged

not specifiedTotal: 283

not providedTotal: 47

Neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalitiesTotal: 7

ObesityTotal: 1

NAV3-associated neurodevelopmental disorderTotal: 1

Broad eyebrowTotal: 1

Sleep apneaTotal: 1

Midface retrusionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001024383.2. 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			5 clinvar	5 clinvar	5 clinvar	15
missense			308 clinvar	5 clinvar	2 clinvar	315
nonsense	1 clinvar	1 clinvar	10 clinvar			12
start loss			1 clinvar			1
frameshift	2 clinvar		2 clinvar			4
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	3	1	336	10	7	357

Highest pathogenic variant AF is 0.0000012419151

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001024383.2	RefSeq	NP_001019554.1	40	MANE Select
ENST00000397909.7	Ensembl	ENSP00000381007.2	40	MANE Select
NM_001438019.1	RefSeq	NP_001424948.1	29	Standard
NM_014903.6	RefSeq	NP_055718.4	39	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nav3	Danio rerio	Structure: liver primordium Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

nav3

Danio rerio

Structure: liver primordium

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glucocorticoid Receptor Pathway
Nuclear Receptors Meta-Pathway

Biological Process

negative regulation of microtubule depolymerization
nervous system development
neurogenesis
negative regulation of cell migration
positive regulation of microtubule polymerization

Molecular Function

ATP binding
microtubule binding

Cellular Component

nuclear outer membrane
microtubule end

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000536525
Coding exons: 39
Length: 382106
Individuals with no LoFs: 124762
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 124794
p: 0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.33	1127	1.26e+3	0.894	0.0000657	15393
Missense (PolyPhen)		449	561.81	0.7992		6929
Synonymous	-1.57	510	467	1.09	0.0000258	4723
Loss of Function	8.42	12	105	0.114	0.00000555	1321

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00015	0.00013	rare
Other	0.00066	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May regulate IL2 production by T-cells. May be involved in neuron regeneration. {ECO:0000269|PubMed:16166283}.;
Disease: DISEASE: Note=A chromosomal aberration disrupting NAV3 has been found in patients with Sezary syndrome (PubMed:16166283). Translocation t(12;18)(q21;q21.2) (PubMed:16166283). {ECO:0000269|PubMed:16166283}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.228
RVIS EVS: -2.05
RVIS percentile EVS: 1.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.655

Gene Damage Prediction

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