NPAS3

Chr 14

neuronal PAS domain protein 3

Also known as: MOP6, PASD6, bHLHe12

NCBI Gene: 64067 ENSG00000151322 UniProt: Q8IXF0

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 5.16

OE 0.08 (0.04–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.14Z-score

OE missense 0.63 (0.58–0.69)

364 obs / 575.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.21)

0≤0.351.4

Missense OE?0.63 (0.58–0.69)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 3 / 36.8Missense obs/exp: 364 / 575.9Syn Z: 0.44

Background carrier burden — how many people carry a rare variant somewhere in NPAS3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

1,322 rare PASS variants

Rare truncating (LoF)

1 in 480

70 rare PASS variants

Rare synonymous (reference)

1 in 55

726 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NPAS3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 69	1 in 600
South Asian	~43k	1 in 51	1 in 460
Remaining (unassigned)	~30k	1 in 48	1 in 2,500
European (Finnish)	~27k	1 in 140	1 in 1,600
Admixed American	~22k	1 in 64	1 in 380
African / African American	~21k	1 in 44	1 in 430
East Asian	~20k	1 in 57	1 in 610
Ashkenazi Jewish	~13k	1 in 240	1 in 930
Middle Eastern	~2,884	1 in 71	≈ 1 in 790

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 12 coding exons well covered in gnomAD exomes; exons 1, 2, 4, 5 poorly covered; exon 3 marginal. Genomes: 11 of 12 (exon 1 below).? see exons ↓