TCTN2

Chr 12AR

tectonic family member 2

Also known as: C12orf38, JBTS24, MKS8, TECT2

This gene encodes a type I membrane protein that is a component of the tectonic-like complex at the ciliary transition zone, where it acts as a barrier preventing diffusion of transmembrane proteins between cilia and plasma membranes and is required for hedgehog signaling transduction. Mutations cause Meckel syndrome type 8 and Joubert syndrome 24, both involving multiple organ systems including the central nervous system, kidneys, and liver. The inheritance pattern is autosomal recessive.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.992 OMIM phenotypes
Clinical SummaryTCTN2
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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.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 28 VUS of 100 total submissions
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GeneReview available — TCTN2
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
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.72 (0.530.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.24Z-score
OE missense 0.97 (0.891.05)
367 obs / 380.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.530.99)
00.351.4
Missense OE0.97 (0.891.05)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 27 / 37.6Missense obs/exp: 367 / 380.0Syn Z: -0.66

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic5
VUS28
Likely Benign43
6
Pathogenic
5
Likely Pathogenic
28
VUS
43
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
2
0
6
Likely Pathogenic
3
0
2
0
5
VUS
2
21
5
0
28
Likely Benign
0
1
21
21
43
Benign
0
0
0
0
0
Total922302182

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

View in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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