NOS1AP

Chr 1AR

nitric oxide synthase 1 adaptor protein

Also known as: 6330408P19Rik, CAPON, NPHS22

NCBI Gene: 9722 ENSG00000198929 UniProt: O75052 OMIM: 605551

The protein functions as an adapter linking neuronal nitric oxide synthase (nNOS) to specific targets including synapsin and RASD1, regulating nitric oxide synthesis and synaptic function, and also activates CDC42 in kidney podocytes to control podosomes and filopodia formation. Mutations cause autosomal recessive nephrotic syndrome type 22, affecting kidney function through disrupted podocyte structure. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.42), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nephrotic syndrome, type 22MIM #619155

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Nephrotic syndrome, type 22; no ClinGen or GenCC tier

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

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.42

LOEUF

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.614

Z-score 3.69

OE 0.20 (0.10–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.04Z-score

OE missense 0.67 (0.60–0.75)

203 obs / 302.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.42)

0≤0.351.4

Missense OE?0.67 (0.60–0.75)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 5 / 24.8Missense obs/exp: 203 / 302.7Syn Z: 1.74

Background carrier burden — how many people carry a rare variant somewhere in NOS1AP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

581 rare PASS variants

Rare truncating (LoF)

1 in 6,500

48 rare PASS variants

Rare synonymous (reference)

1 in 250

290 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NOS1AP. 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 200	1 in 7,000
South Asian	~43k	1 in 150	1 in 2,700
Remaining (unassigned)	~30k	1 in 180	1 in 6,000
European (Finnish)	~27k	1 in 420	1 in 5,200
Admixed American	~22k	1 in 150	≈ 1 in 21,000
African / African American	~21k	1 in 140	≈ 1 in 10,000
East Asian	~20k	1 in 140	none seen
Ashkenazi Jewish	~13k	1 in 750	none seen
Middle Eastern	~2,884	1 in 160	none seen

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): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓