LITAF

Chr 16AD

lipopolysaccharide induced TNF factor

Also known as: PIG7, SIMPLE, TP53I7

NCBI Gene: 9516ENSG00000189067UniProt: Q99732

Lipopolysaccharide is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. This gene encodes lipopolysaccharide-induced TNF-alpha factor, which is a DNA-binding protein and can mediate the TNF-alpha expression by direct binding to the promoter region of the TNF-alpha gene. The transcription of this gene is induced by tumor suppressor p53 and has been implicated in the p53-induced apoptotic pathway. Mutations in this gene cause Charcot-Marie-Tooth disease type 1C (CMT1C) and may be involved in the carcinogenesis of extramammary Paget's disease (EMPD). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2014]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 1CMIM #601098
AD
339
ClinVar variants
25
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— LITAF
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 168 VUS of 339 total submissions

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.
1.28LOEUF
pLI 0.031
Z-score 1.13
OE 0.50 (0.23–1.28)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.22Z-score
OE missense 0.94 (0.80–1.11)
97 obs / 103.4 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.0.50 (0.23–1.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.80–1.11)
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.1.03
0≤1.21.6
LoF obs/exp: 3 / 6.0Missense obs/exp: 97 / 103.4Syn Z: -0.18

ClinVar Variant Classifications

339 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic5
VUS168
Likely Benign75
Benign53
Conflicting18
20
Pathogenic
5
Likely Pathogenic
168
VUS
75
Likely Benign
53
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
5
15
0
20
Likely Pathogenic
0
3
2
0
5
VUS
4
102
59
3
168
Likely Benign
0
5
25
45
75
Benign
0
4
48
1
53
Conflicting
—18
Total411914949339

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

View in ClinVar →

Protein Context — Lollipop Plot

LITAF · 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

Charcot-Marie-Tooth disease, type 1C

MIM #601098

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — LITAF
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Current Challenges and Opportunities in Treating Glioblastoma.
Shergalis A et al.·Pharmacol Rev
2018
Identification and clinical characterization of Charcot-Marie-Tooth disease type 1C patients with LITAF p.G112S mutation.
Park J et al.·Genes Genomics
2022Cohort
A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?
Kamińska J et al.·Int J Mol Sci
2024Review
Whole genome sequencing analysis in primary lateral sclerosis (PLS) patients reveals mutations in neurological diseases-causing genes.
Manini A et al.·J Neurol
2025Cohort
miRNA-106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation.
Hoey C et al.·Mol Oncol
2018
LITAF-NOTCH2-Bmi-1 Axis Mediates AMPK-Dependent Inhibition of Gastric Cancer Invasion and Metastasis.
Li Y et al.·FASEB J
2025
The topology, structure and PE interaction of LITAF underpin a Charcot-Marie-Tooth disease type 1C.
Ho AK et al.·BMC Biol
2016
LITAF (Lipopolysaccharide-Induced Tumor Necrosis Factor) Regulates Cardiac L-Type Calcium Channels by Modulating NEDD (Neural Precursor Cell Expressed Developmentally Downregulated Protein) 4-1 Ubiquitin Ligase.
Moshal KS et al.·Circ Genom Precis Med
2019
Involvement of the MicroRNA-1-LITAF Axis in Gastric Cancer Cell Growth and Invasion.
Chen YC et al.·Anticancer Res
2020
The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases.
Sinkiewicz-Darol E et al.·Neurogenetics
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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