NOSTRIN

Chr 2

nitric oxide synthase trafficking

Also known as: DaIP2

NCBI Gene: 115677 ENSG00000163072 UniProt: Q8IVI9 OMIM: 607496

Nitric oxide (NO) is a potent mediator in biologic processes such as neurotransmission, inflammatory response, and vascular homeostasis. NOSTRIN binds the enzyme responsible for NO production, endothelial NO synthase (ENOS; MIM 163729), and triggers the translocation of ENOS from the plasma membrane to vesicle-like subcellular structures, thereby attenuating ENOS-dependent NO production.[supplied by OMIM, Apr 2004]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.09

Clinical Summary— NOSTRIN

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 VUS of 64 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.000

Z-score 1.11

OE 0.80 (0.59–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.64Z-score

OE missense 0.89 (0.80–0.99)

247 obs / 277.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.59–1.09)

0≤0.351.4

Missense OE?0.89 (0.80–0.99)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 28 / 35.1Missense obs/exp: 247 / 277.2Syn Z: -0.07

This gene — mechanism propensity

0.6258th %ile

GOF

0.4381th %ile

LOF

0.4135th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Likely Benign3

Benign2

Conflicting1

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	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	39	0	0	39
Likely Benign	0	3	0	0	3
Benign	0	2	0	0	2
Conflicting	—				1
Total	0	44	0	0	45

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap NOSTRIN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →