TCTN2

Chr 12AR

tectonic family member 2

Also known as: C12orf38, JBTS24, MKS8, TECT2

NCBI Gene: 79867 ENSG00000168778 OMIM: 613846

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a type I membrane protein that belongs to the tectonic family. Studies in mice suggest that this protein may be involved in hedgehog signaling, and essential for ciliogenesis. Mutations in this gene are associated with Meckel syndrome type 8. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.992 OMIM phenotypes

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.

📋

ClinVar Variants

58 unique Pathogenic / Likely Pathogenic· 240 VUS of 583 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — TCTN2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.60

OE 0.72 (0.53–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.24Z-score

OE missense 0.97 (0.89–1.05)

367 obs / 380.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.53–0.99)

0≤0.351.4

Missense OE?0.97 (0.89–1.05)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 27 / 37.6Missense obs/exp: 367 / 380.0Syn Z: -0.66

ClinVar Variant Classifications

583 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic38

VUS240

Likely Benign239

Benign20

Conflicting8

Pathogenic

Likely Pathogenic

240

VUS

239

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	0	2	0	20
Likely Pathogenic	34	2	2	0	38
VUS	4	203	27	6	240
Likely Benign	0	2	125	112	239
Benign	0	0	20	0	20
Conflicting	—				8
Total	56	207	176	118	565

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap TCTN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →