TNIP2

Chr 4

TNFAIP3 interacting protein 2

Also known as: ABIN2, FLIP1, KLIP

NCBI Gene: 79155 ENSG00000168884 UniProt: Q8NFZ5 OMIM: 610669

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein which acts as an inhibitor of NFkappaB activation. The encoded protein is also involved in MAP/ERK signaling pathway in specific cell types. It may be involved in apoptosis of endothelial cells. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the X chromosome.[provided by RefSeq, May 2014]

OMIM ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.74

LOEUF

Mechanism· predicted

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 OE?0.41 (0.24–0.74)

0≤0.351.4

Missense OE?0.91 (0.81–1.02)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 19.6Missense obs/exp: 219 / 240.7Syn Z: -0.20

Background carrier burden — how many people carry a rare variant somewhere in TNIP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 74

635 rare PASS variants

Rare truncating (LoF)

1 in 3,000

75 rare PASS variants

Rare synonymous (reference)

1 in 120

278 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TNIP2. 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 110	1 in 3,200
South Asian	~43k	1 in 53	1 in 2,100
Remaining (unassigned)	~30k	1 in 69	1 in 3,200
European (Finnish)	~27k	1 in 160	1 in 4,700
Admixed American	~22k	1 in 98	1 in 4,300
African / African American	~21k	1 in 61	1 in 1,700
East Asian	~20k	1 in 100	≈ 1 in 5,600
Ashkenazi Jewish	~13k	1 in 210	none seen
Middle Eastern	~2,884	1 in 61	≈ 1 in 2,900

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): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓