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…

ARLOEUF 0.421 OMIM phenotype

Clinical Summary— NOS1AP

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 63 VUS of 124 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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

ClinVar Variant Classifications

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS63

Likely Benign10

Benign35

Conflicting1

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	1	0	2
Likely Pathogenic	0	0	0	0	0
VUS	0	59	4	0	63
Likely Benign	0	2	2	6	10
Benign	0	1	25	9	35
Conflicting	—				1
Total	0	63	32	15	111

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap NOS1AP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →