TNIP2

Chr 4

TNFAIP3 interacting protein 2

Also known as: ABIN2, FLIP1, KLIP

NCBI Gene: 79155ENSG00000168884UniProt: Q8NFZ5

TNIP2 encodes a protein that inhibits NF-kappa-B activation and regulates MAP/ERK signaling pathways during innate immune responses, while also promoting endothelial cell survival. Mutations cause autosomal dominant autoinflammatory disease with immunodeficiency, presenting with recurrent infections, inflammatory episodes, and potential endothelial dysfunction. The gene shows low constraint to loss-of-function variants (pLI 0.002, LOEUF 0.74), suggesting tolerance to protein-truncating mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
128
P/LP submissions
0%
P/LP missense
0.74
LOEUF
DN
Mechanism· predicted
Clinical Summary— TNIP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
128 unique Pathogenic / Likely Pathogenic· 87 VUS of 229 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
0.74LOEUF
pLI 0.002
Z-score 2.43
OE 0.41 (0.24–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.50Z-score
OE missense 0.91 (0.81–1.02)
219 obs / 240.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.24–0.74)
0≤0.351.4
Missense OE0.91 (0.81–1.02)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 8 / 19.6Missense obs/exp: 219 / 240.7Syn Z: -0.20
DN
0.6454th %ile
GOF
0.6052th %ile
LOF
0.3164th %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

229 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic123
Likely Pathogenic5
VUS87
Likely Benign4
123
Pathogenic
5
Likely Pathogenic
87
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
123
0
123
Likely Pathogenic
0
0
5
0
5
VUS
0
79
8
0
87
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total0831360219

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

View in ClinVar →

Protein Context — Lollipop Plot

TNIP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients