TNFAIP8

Chr 5

TNF alpha induced protein 8

Also known as: GG2-1, MDC-3.13, NDED, SCC-S2, SCCS2

NCBI Gene: 25816ENSG00000145779UniProt: O95379

Enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process. Involved in positive regulation of apoptotic process. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

50
ClinVar variants
20
Pathogenic / LP
0.38
pLI score
1
Active trials
Clinical Summary— TNFAIP8
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 29 VUS of 50 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.97LOEUF
pLI 0.385
Z-score 1.63
OE 0.20 (0.07–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.45Z-score
OE missense 0.88 (0.74–1.04)
90 obs / 102.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.07–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.74–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 1 / 4.9Missense obs/exp: 90 / 102.7Syn Z: -0.11

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
VUS29
Likely Benign1
20
Pathogenic
29
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
0
0
0
VUS
0
21
8
0
29
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02129050

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

View in ClinVar →

Protein Context — Lollipop Plot

TNFAIP8 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification and validation of glycolysis-related diagnostic signatures in diabetic nephropathy: a study based on integrative machine learning and single-cell sequence.
Wu X et al.·Front Immunol
2025
Current research status of TNFAIP8 in tumours and other inflammatory conditions (Review).
Hua J et al.·Int J Oncol
2021Review
TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma.
Tian M et al.·Elife
2024
Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes.
Shi TY et al.·Carcinogenesis
2013Functional
TNFAIP8 overexpression: clinical relevance to esophageal squamous cell carcinoma.
Hadisaputri YE et al.·Ann Surg Oncol
2012
TNFAIP8 promotes the proliferation and cisplatin chemoresistance of non-small cell lung cancer through MDM2/p53 pathway.
Xing Y et al.·Cell Commun Signal
2018
Tumor Necrosis Factor-α Induced Protein 8: Pathophysiology, Clinical Significance, and Regulatory Mechanism.
Zhang L et al.·Int J Biol Sci
2018Review
TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma.
Dong Q et al.·Oncotarget
2017
Correlation of TNFAIP8 overexpression with the proliferation, metastasis, and disease-free survival in endometrial cancer.
Liu T et al.·Tumour Biol
2014
The novel p53 target TNFAIP8 variant 2 is increased in cancer and offsets p53-dependent tumor suppression.
Lowe JM et al.·Cell Death Differ
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
An Insulin-Exosome-TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer.
Li Z et al.·Adv Sci (Weinh)
2026
TNFAIP8 targets ATG3 to regulate autophagy and participate in the molecular mechanism of ankylosing spondylitis.
Zhao Y et al.·Immunol Lett
2026Functional
TNFAIP8 Deficiency Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Inflammation Via TLR4/NF-κB Signaling.
Chen L et al.·Cardiovasc Toxicol
2025
Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis.
Zhang X et al.·Discov Oncol
2025🔓 Open Access
MiR-455-5p Mitigates Interleukin-1 β-induced Chondrocyte Damage Linked to Osteoarthritis by Targeting TNFAIP8.
Zhang T et al.·J Physiol Investig
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Concussion, BrainMild Traumatic Brain Injury

Risk Stratification in Children With Concussion

RECRUITING
NCT05825027Duke UniversityStarted 2023-05-23

External Resources

Links to major genomics databases and tools