TCTN1

Chr 12AR

tectonic family member 1

Also known as: JBTS13, TECT1

NCBI Gene: 79600ENSG00000204852UniProt: Q2MV58

This gene encodes a member of a family of secreted and transmembrane proteins. The orthologous gene in mouse functions downstream of smoothened and rab23 to modulate hedgehog signal transduction. This protein is a component of the tectonic-like complex, which forms a barrier between the ciliary axoneme and the basal body. A mutation in this gene was found in a family with Joubert syndrome-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Primary Disease Associations & Inheritance

Joubert syndrome 13MIM #614173
AR
524
ClinVar variants
69
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TCTN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 184 VUS of 524 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.
1.23LOEUF
pLI 0.000
Z-score 0.58
OE 0.88 (0.64–1.23)
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.
0.61Z-score
OE missense 0.90 (0.82–1.00)
282 obs / 312.1 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.0.88 (0.64–1.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–1.00)
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.0.85
0≤1.21.6
LoF obs/exp: 25 / 28.3Missense obs/exp: 282 / 312.1Syn Z: 1.32

ClinVar Variant Classifications

524 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic34
VUS184
Likely Benign203
Benign18
Conflicting9
35
Pathogenic
34
Likely Pathogenic
184
VUS
203
Likely Benign
18
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
0
17
0
35
Likely Pathogenic
25
2
7
0
34
VUS
2
166
12
4
184
Likely Benign
2
9
80
112
203
Benign
0
0
18
0
18
Conflicting
—9
Total47177134116483

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

View in ClinVar →

Protein Context — Lollipop Plot

TCTN1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TCTN1-related Joubert syndrome and related disorders

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Joubert syndrome 13

MIM #614173

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TCTN1 Induces Fatty Acid Oxidation to Promote Melanoma Metastasis.
Li Y et al.·Cancer Res
2025
Ocular manifestations of renal ciliopathies.
Salehi O et al.·Pediatr Nephrol
2024Review
Function and transcriptional regulation of TCTN1 in oral squamous cell carcinoma.
Bai G et al.·Oncol Rep
2022
Clinical and molecular characteristics of tectonic (TCTN1) gene-related Joubert syndrome in a Saudi boy.
Shirah BH et al.·Brain Dev
2022Case report
Tectonic‑1 contributes to the growth and migration of prostate cancer cells in vitro.
Wang Z et al.·Int J Mol Med
2015
Tectonic 1 Is a Key Regulator of Cell Proliferation in Pancreatic Cancer.
Zhao S et al.·Cancer Biother Radiopharm
2016
Expression and prognostic significance of TCTN1 in human glioblastoma.
Meng D et al.·J Transl Med
2014
Variant Spectrum of Renal Ciliopathies in Turkish Cohort and Genotype-Phenotype Association Specifically in Autosomal Dominant Polycystic Kidney Disease.
Ercoskun P et al.·Clin Genet
2025Cohort
Clinical and Molecular Diagnosis of Joubert Syndrome and Related Disorders.
Radha Rama Devi A et al.·Pediatr Neurol
2020
Tectonic Proteins Are Important Players in Non-Motile Ciliopathies.
Gong S et al.·Cell Physiol Biochem
2018Review
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