Tenascin-C is an extracellular matrix protein that guides migrating neurons and axons during development, promotes synaptic plasticity and neuronal regeneration, and serves as a ligand for several integrins. Mutations cause autosomal dominant deafness (DFNA56). The gene is highly constrained against loss-of-function variants (LOEUF 0.445), indicating that such variants are likely pathogenic.

OMIMResearchSummary from OMIM, UniProt
MultiplemechanismADLOEUF 0.451 OMIM phenotype
Clinical SummaryTNC
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.000
Z-score 5.95
OE 0.33 (0.240.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.08Z-score
OE missense 1.01 (0.961.05)
1296 obs / 1287.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.33 (0.240.45)
00.351.4
Missense OE1.01 (0.961.05)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 30 / 91.4Missense obs/exp: 1296 / 1287.7Syn Z: -0.33
DN
0.74top 25%
GOF
0.6735th %ile
LOF
0.2968th %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
GOFprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TNC · 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 →