TCTN2

Chr 12AR

tectonic family member 2

ENSG00000168778UniProt: Q96GX1

Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for hedgehog signaling transduction (By similarity)

Primary Disease Associations & Inheritance

?Meckel syndrome 8MIM #613885
AR
Joubert syndrome 24MIM #616654
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TCTN2
🧬
Gene-Disease Validity (ClinGen)
Joubert syndrome 24 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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

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.
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.72 (0.53–0.99)
Tolerant

Typical tolerance to LoF variation

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.
0.24Z-score
OE missense 0.97 (0.89–1.05)
367 obs / 380.0 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.0.72 (0.53–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.89–1.05)
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.1.07
0≤1.21.6
LoF obs/exp: 27 / 37.6Missense obs/exp: 367 / 380.0Syn Z: -0.66

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TCTN2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TCTN2-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

?Meckel syndrome 8

MIM #613885

Molecular basis of disorder known

Autosomal recessive

Joubert syndrome 24

MIM #616654

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TCTN2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Establishing dorsal-ventral patterning in human neural tube organoids with synthetic organizers.
Luo T et al.·Cell Stem Cell
2025
Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and Ciliary Weakening.
Weng RR et al.·Biophys J
2018
LncRNA TCTN2 Promotes the Malignant Development of Hepatocellular Carcinoma via Regulating mIR-1285-3p/ARF6 Axis.
Liu Q et al.·Recent Pat Anticancer Drug Discov
2023
Overexpression of lncRNA TCTN2 protects neurons from apoptosis by enhancing cell autophagy in spinal cord injury.
Ren XD et al.·FEBS Open Bio
2019
Two novel TCTN2 mutations cause Meckel-Gruber syndrome.
Zhang M et al.·J Hum Genet
2020
Tectonic Proteins Are Important Players in Non-Motile Ciliopathies.
Gong S et al.·Cell Physiol Biochem
2018Review
Novel variants identified in five Chinese families with Joubert Syndrome: a case report.
Fang L et al.·BMC Med Genomics
2023Case report
Novel Compound Heterozygous Variants in the TCTN2 Gene Causing Meckel-Gruber Syndrome 8 in a Non-Consanguineous Chinese Family.
Yang Q et al.·Mol Genet Genomic Med
2025Case report
A TCTN2 mutation defines a novel Meckel Gruber syndrome locus.
Shaheen R et al.·Hum Mutat
2011
A deep intronic TCTN2 variant activating a cryptic exon predicted by SpliceRover in a patient with Joubert syndrome.
Hiraide T et al.·J Hum Genet
2023
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