NPAS3

protein-coding

neuronal PAS domain protein 3, the group of PAS domain containing|Basic helix-loop-helix proteins

Gene summary

This gene encodes a member of the basic helix-loop-helix and PAS domain-containing family of transcription factors. The encoded protein is localized to the nucleus and may regulate genes involved in neurogenesis. Chromosomal abnormalities that affect the coding potential of this gene are associated with schizophrenia and cognitive disability. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

MANE transcript

NM_001164749.2

Inheritance

ClinVar variants

U:122B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr14:32,934,396-33,820,863

External References & Databases

Ensembl (ENSG00000151322)

Transcript & Mutation Effects

hg38 • Region Span ~886.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PMGRC

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NPAS3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 116

not providedTotal: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001164749.2. 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				7 clinvar	4 clinvar	11
missense			116 clinvar	3 clinvar	1 clinvar	120
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	122	10	5	137

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001164749.2	RefSeq	NP_001158221.1	12	MANE Select
ENST00000356141.9	Ensembl	ENSP00000348460.4	12	MANE Select
NM_001165893.2	RefSeq	NP_001159365.1	11	Standard
NM_001394988.1	RefSeq	NP_001381917.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
positive regulation of transcription, DNA-templated
positive regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
protein heterodimerization activity

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356141
Coding exons: 12
Length: 869244
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.14	364	576	0.632	0.0000364	6016
Missense (PolyPhen)		107	176.12	0.60755		1802
Synonymous	0.445	251	260	0.965	0.0000199	1873
Loss of Function	5.16	3	36.8	0.0815	0.00000204	405

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a broad role in neurogenesis. May control regulatory pathways relevant to schizophrenia and to psychotic illness (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.347
RVIS EVS: -1.35
RVIS percentile EVS: 4.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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