IVNS1ABP

Chr 1AD

influenza virus NS1A binding protein

Also known as: ARA3, FLARA3, HSPC068, IMD70, KLHL39, ND1, NS-1, NS1-BP

NCBI Gene: 10625 ENSG00000116679 UniProt: Q9Y6Y0 OMIM: 609209

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Involved in RNA splicing; negative regulation of protein ubiquitination; and response to virus. Located in cytosol. Implicated in immunodeficiency 70. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.281 OMIM phenotype

Clinical Summary— IVNS1ABP

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 42 VUS of 70 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.994

Z-score 4.91

OE 0.13 (0.07–0.28)

Highly constrained

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

Missense Constraint?

2.89Z-score

OE missense 0.56 (0.50–0.63)

192 obs / 342.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.28)

0≤0.351.4

Missense OE?0.56 (0.50–0.63)

0≤0.61.4

Synonymous OE?0.77

0≤1.21.6

LoF obs/exp: 5 / 37.5Missense obs/exp: 192 / 342.2Syn Z: 1.93

This gene — mechanism propensity

0.4091th %ile

GOF

0.4283th %ile

LOF

0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.28

Literature Evidence

LOFWestern blot analysis of peripheral blood cells from 1 patient (kindred A) showed a 50% reduction in IVNS1AB protein compared to controls, consistent with haploinsufficiency.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 32499645 ↗

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS42

Likely Benign9

Conflicting1

Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	1	0	3
Likely Pathogenic	0	0	0	0	0
VUS	1	41	0	0	42
Likely Benign	0	2	4	3	9
Benign	0	0	0	0	0
Conflicting	—				1
Total	3	43	5	3	55

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap IVNS1ABP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →