TNR

Chr 1AR

tenascin R

Also known as: NEDSTO, TN-R

NCBI Gene: 7143ENSG00000116147UniProt: Q92752

This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The encoded protein is restricted to the central nervous system. The protein may play a role in neurite outgrowth, neural cell adhesion and modulation of sodium channel function. It is a constituent of perineuronal nets. [provided by RefSeq, Aug 2013]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonusMIM #619653
AR
318
ClinVar variants
41
Pathogenic / LP
0.52
pLI score
0
Active trials
Clinical Summary— TNR
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.
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ClinVar Variants
41 Pathogenic / Likely Pathogenic· 219 VUS of 318 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.34LOEUF
pLI 0.524
Z-score 6.14
OE 0.22 (0.15–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
1.60Z-score
OE missense 0.84 (0.79–0.90)
685 obs / 813.0 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.0.22 (0.15–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.79–0.90)
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.1.04
0≤1.21.6
LoF obs/exp: 16 / 72.4Missense obs/exp: 685 / 813.0Syn Z: -0.51

ClinVar Variant Classifications

318 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic5
VUS219
Likely Benign40
Benign14
Conflicting4
36
Pathogenic
5
Likely Pathogenic
219
VUS
40
Likely Benign
14
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
2
30
0
36
Likely Pathogenic
1
2
2
0
5
VUS
0
206
13
0
219
Likely Benign
0
11
2
27
40
Benign
0
3
3
8
14
Conflicting
—4
Total52245035318

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

View in ClinVar →

Protein Context — Lollipop Plot

TNR · 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
TENASCIN R; TNR
MIM #601995 · *

Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus

MIM #619653

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A TNR Frameshift Variant in Weimaraner Dogs with an Exercise-Induced Paroxysmal Movement Disorder.
Christen M et al.·Mov Disord
2023
Base editing of trinucleotide repeats that cause Huntington's disease and Friedreich's ataxia reduces somatic repeat expansions in patient cells and in mice.
Matuszek Z et al.·Nat Genet
2025
Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma.
Vasilijic S et al.·Sci Adv
2023Cohort
A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice.
Yang H et al.·EBioMedicine
2024
Whole exome sequencing revealed ultra-rare genetic variations in juvenile myoclonic epilepsy.
Yacoub AM et al.·Neurol Sci
2025
Prediction of thyroid malignancy risk using clinical and ultrasonography features and a machine learning approach.
Hosseini Sarkhosh SM et al.·Eur Radiol
2025
Faulty splicing and cytoskeleton abnormalities in Huntington's disease.
Fernández-Nogales M et al.·Brain Pathol
2016Review
Epigenetic modifications in trinucleotide repeat diseases.
Evans-Galea MV et al.·Trends Mol Med
2013Review
Unveiling Macrophage Content as a Predictive Biomarker for Intraoperative ICG Imaging Efficacy in Lung Cancer.
Yan Y et al.·Adv Sci (Weinh)
2025
Small nuclear RNAs U11 and U12 modulate expression of TNR-CFTR mRNA in mammalian kidneys.
Souza-Menezes J et al.·Cell Physiol Biochem
2008
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