NETO1

protein-coding

neuropilin and tolloid like 1, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes a transmembrane protein containing two extracellular CUB domains followed by a low-density lipoprotein class A (LDLa) domain. This protein is thought to play a critical role in spatial learning and memory by regulating the function of synaptic N-methyl-D-aspartic acid receptor complexes in the hippocampus. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2017]

MANE transcript

NM_138966.5

Inheritance

—

ClinVar variants

U:50B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr18:72,742,314-72,868,146

External References & Databases

Ensembl (ENSG00000166342)

Transcript & Mutation Effects

hg38 • Region Span ~125.8 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 NETO1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138966.5. 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
missense			47 clinvar	2 clinvar	2 clinvar	51
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	2	2	54

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138966.5	RefSeq	NP_620416.2	10	MANE Select
ENST00000327305.11	Ensembl	ENSP00000313088.6	10	MANE Select
NM_001201465.3	RefSeq	NP_001188394.2	10	Standard
NM_001354017.2	RefSeq	NP_001340946.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

memory
visual learning
regulation of long-term neuronal synaptic plasticity
receptor localization to synapse
regulation of kainate selective glutamate receptor activity

Molecular Function

ionotropic glutamate receptor binding

Cellular Component

extracellular region
postsynaptic density
cell junction
excitatory synapse
postsynaptic density membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327305
Coding exons: 10
Length: 125833
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.80	213	301	0.708	0.0000162	3524
Missense (PolyPhen)		68	125.04	0.54383		1412
Synonymous	-0.303	110	106	1.04	0.00000574	984
Loss of Function	3.62	8	29.1	0.275	0.00000180	313

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.00011	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the development and/or maintenance of neuronal circuitry. Accessory subunit of the neuronal N-methyl-D- aspartate receptor (NMDAR) critical for maintaining the abundance of GRIN2A-containing NMDARs in the postsynaptic density. Regulates long-term NMDA receptor-dependent synaptic plasticity and cognition, at least in the context of spatial learning and memory (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.393

Intolerance Scores

LoFtool: 0.443
RVIS EVS: 0.75
RVIS percentile EVS: 86.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.219

Gene Damage Prediction

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