LITAF

Chr 16AD

lipopolysaccharide induced TNF factor

Also known as: PIG7, SIMPLE, TP53I7

The LITAF protein is a DNA-binding transcription factor that regulates TNF-alpha expression and mediates p53-induced apoptosis. Mutations cause Charcot-Marie-Tooth disease type 1C (CMT1C) through an autosomal dominant inheritance pattern with a dominant-negative mechanism. The pathogenic variants likely disrupt the protein's normal transcriptional regulatory functions, leading to the peripheral neuropathy characteristic of CMT1C.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 1.281 OMIM phenotype
Clinical SummaryLITAF
🧬
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.
📖
GeneReview available — LITAF
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.031
Z-score 1.13
OE 0.50 (0.231.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.22Z-score
OE missense 0.94 (0.801.11)
97 obs / 103.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.231.28)
00.351.4
Missense OE0.94 (0.801.11)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 3 / 6.0Missense obs/exp: 97 / 103.4Syn Z: -0.18
DN
0.79top 25%
GOF
0.73top 25%
LOF
0.2387th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
GOFprediction above median · 1 literature citation

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.

Literature Evidence

DNThe findings suggested that the W116G Litaf mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms.PMID:23359569
GOFThe findings suggested that the W116G Litaf mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms.PMID:23359569

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →