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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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TCTN3
tectonic family member 3
Chromosome 10 Β· 10q24.1
NCBI Gene: 26123Ensembl: ENSG00000119977.22HGNC: HGNC:24519UniProt: A0A7P0TB57
40PubMed Papers
22Diseases
0Drugs
69Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsmoothened signaling pathwaypositive regulation of apoptotic processnucleusorofaciodigital syndrome IVJoubert syndrome 18Orofaciodigital syndrome type 4Joubert syndrome with orofaciodigital defect
✦AI Summary

TCTN3 (tectonic family member 3) is a ciliary transition zone protein essential for primary cilia assembly and function. 1 It localizes to the ciliary transition zone and is a critical component of the tectonic protein complex required for ciliogenesis and regulation of ciliary membrane composition. 1 TCTN3 plays a vital role in sonic hedgehog (Shh) signaling pathway regulation, with tectonic-deficient models showing Shh-related developmental defects. 1 Pathogenic TCTN3 variants cause primary ciliopathies characterized by mid-hindbrain malformation. Mutations underlie Joubert syndrome 18, presenting with cerebellar vermis agenesis, the diagnostic molar tooth sign on brain MRI, ataxia, cognitive impairment, and abnormal eye movements. 2 3 TCTN3 variants also cause orofaciodigital syndrome type 4 (OFD4), featuring oral cavity and facial abnormalities, digit defects, and growth retardation, with some cases displaying atypical features including scaphocephaly and seizures. 4 Additional manifestations in TCTN3-related disorders include polydactyly, encephalocele, and congenital heart disease with reduced cardiomyocyte contractility. 5 6 Recently, TCTN3 has been implicated in papillary thyroid carcinoma progression through STAT1-mediated upregulation, promoting cell-cycle progression, migration, and invasion. 7 These findings expand TCTN3's roles beyond developmental ciliopathies to cancer biology.

Sources cited
1
TCTN3 variants cause Joubert syndrome 18 characterized by cerebellar vermis agenesis, molar tooth sign, ataxia, cognitive impairment, and dystonic movements
PMID: 40565597
2
TCTN3 is a transition zone protein component required for ciliogenesis, ciliary membrane composition regulation, and sonic hedgehog pathway signaling
PMID: 30286481
3
TCTN3 mutations were identified in Joubert syndrome patients among 35 ciliopathy-related genes
PMID: 32139166
4
TCTN3 splice site variants cause orofaciodigital syndrome type 4 with limb defects, growth retardation, and atypical features including scaphocephaly and seizures
PMID: 36039988
5
TCTN3 pathogenic variants cause OFD type IV with occipital encephalocele and arm anomalies
PMID: 35170189
6
TCTN3 mutations reduce contractility rate and force of cardiac myocytes in congenital heart disease with polydactyly
PMID: 33098376
7
STAT1 promotes TCTN3 expression through direct promoter binding, driving papillary thyroid carcinoma progression via cell-cycle acceleration and tumor cell migration/invasion
PMID: 41581815
Disease Associationsβ“˜22
orofaciodigital syndrome IVOpen Targets
0.79Strong
Joubert syndrome 18Open Targets
0.78Strong
Orofaciodigital syndrome type 4Open Targets
0.77Strong
Joubert syndrome with orofaciodigital defectOpen Targets
0.65Moderate
Joubert syndromeOpen Targets
0.62Moderate
Joubert syndrome and related disordersOpen Targets
0.51Moderate
ciliopathyOpen Targets
0.44Moderate
diverticular diseaseOpen Targets
0.44Moderate
genetic disorderOpen Targets
0.41Moderate
Meckel syndromeOpen Targets
0.37Weak
orofaciodigital syndrome type 6Open Targets
0.37Weak
preeclampsiaOpen Targets
0.28Weak
early-onset non-syndromic cataractOpen Targets
0.11Weak
Total congenital cataractOpen Targets
0.09Suggestive
Partial congenital cataractOpen Targets
0.09Suggestive
Cataract-microcornea syndromeOpen Targets
0.09Suggestive
early-onset nuclear cataractOpen Targets
0.08Suggestive
isolated ectopia lentisOpen Targets
0.08Suggestive
early-onset zonular cataractOpen Targets
0.08Suggestive
Posterior polar cataractOpen Targets
0.07Suggestive
Joubert syndrome 18UniProt
Orofaciodigital syndrome 4UniProt
Pathogenic Variants69
NM_015631.6(TCTN3):c.276_277del (p.Cys92_Asp93delinsTer)Pathogenic
not provided|Orofacial-digital syndrome IV;Joubert syndrome 18
β˜…β˜…β˜†β˜†2026β†’ Residue 92
NM_015631.6(TCTN3):c.256+2_256+7delLikely pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18|Joubert syndrome and related disorders|not provided
β˜…β˜…β˜†β˜†2026
NM_015631.6(TCTN3):c.338_341del (p.His113fs)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18|TCTN3-related disorder|Joubert syndrome and related disorders
β˜…β˜…β˜†β˜†2026β†’ Residue 113
NM_015631.6(TCTN3):c.877C>T (p.Gln293Ter)Pathogenic
Orofacial-digital syndrome IV|Joubert syndrome 18;Orofacial-digital syndrome IV
β˜…β˜…β˜†β˜†2025β†’ Residue 293
NM_015631.6(TCTN3):c.1520dup (p.Gly508fs)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18|Joubert syndrome and related disorders
β˜…β˜…β˜†β˜†2025β†’ Residue 508
NM_015631.6(TCTN3):c.182dup (p.Gly62fs)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18|Ciliopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 62
NM_015631.6(TCTN3):c.2T>G (p.Met1Arg)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18|Joubert syndrome and related disorders|TCTN3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_015631.6(TCTN3):c.1327C>T (p.Gln443Ter)Pathogenic
Orofacial-digital syndrome IV|Orofacial-digital syndrome IV;Joubert syndrome 18|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 443
NM_015631.6(TCTN3):c.1096-2A>GLikely pathogenic
Joubert syndrome 18;Orofacial-digital syndrome IV
β˜…β˜…β˜†β˜†2025
NM_015631.6(TCTN3):c.3G>A (p.Met1Ile)Pathogenic
Joubert syndrome 18|Orofacial-digital syndrome IV;Joubert syndrome 18|not provided|Joubert syndrome and related disorders
β˜…β˜…β˜†β˜†2024β†’ Residue 1
NM_015631.6(TCTN3):c.622dup (p.Tyr208fs)Pathogenic
Joubert syndrome and related disorders|Orofacial-digital syndrome IV;Joubert syndrome 18
β˜…β˜…β˜†β˜†2024β†’ Residue 208
NM_015631.6(TCTN3):c.940G>T (p.Gly314Ter)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18|Joubert syndrome and related disorders
β˜…β˜…β˜†β˜†2024β†’ Residue 314
NM_015631.6(TCTN3):c.776dup (p.Lys260fs)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18
β˜…β˜…β˜†β˜†2024β†’ Residue 260
NM_015631.6(TCTN3):c.710del (p.Gly237fs)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18
β˜…β˜…β˜†β˜†2024β†’ Residue 237
NM_015631.6(TCTN3):c.650_653del (p.Tyr217fs)Pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18|Orofacial-digital syndrome IV
β˜…β˜…β˜†β˜†2024β†’ Residue 217
NM_015631.6(TCTN3):c.1A>G (p.Met1Val)Pathogenic
Joubert syndrome 18|Orofacial-digital syndrome IV;Joubert syndrome 18
β˜…β˜…β˜†β˜†2023β†’ Residue 1
NM_015631.6(TCTN3):c.910dup (p.Thr304fs)Pathogenic
Inborn genetic diseases|Orofacial-digital syndrome IV;Joubert syndrome 18
β˜…β˜…β˜†β˜†2022β†’ Residue 304
NM_015631.6(TCTN3):c.711del (p.Leu238fs)Pathogenic
Joubert syndrome 18;Orofacial-digital syndrome IV
β˜…β˜†β˜†β˜†2026β†’ Residue 238
NM_015631.6(TCTN3):c.970-2A>GLikely pathogenic
Orofacial-digital syndrome IV;Joubert syndrome 18
β˜…β˜†β˜†β˜†2026
NM_015631.6(TCTN3):c.662G>A (p.Trp221Ter)Pathogenic
Joubert syndrome 18;Orofacial-digital syndrome IV
β˜…β˜†β˜†β˜†2025β†’ Residue 221
View on ClinVar β†—
Related Genes
TMEM67Protein interaction99%TMEM216Protein interaction99%NPHP1Protein interaction98%CEP290Protein interaction97%AHI1Protein interaction97%TMEM107Protein interaction94%
Tissue Expression6 tissues
Ovary
100%
Lung
68%
Liver
67%
Brain
60%
Heart
60%
Bone Marrow
36%
Gene Interaction Network
Click a node to explore
TCTN3TMEM67TMEM216NPHP1CEP290AHI1TMEM107
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6NUS6
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.94LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.59–0.94]
RankingsWhere TCTN3 stands among ~20K protein-coding genes
  • #10,252of 20,598
    Most Researched40
  • #1,058of 5,498
    Most Pathogenic Variants69 Β· top quartile
  • #8,722of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedTCTN3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301500
1.00
2
Expansion of the Genotypic and Phenotypic Spectrum of
PMID: 40565597
Genes (Basel) Β· 2025
0.90
3
Prenatally detected encephalocele associated with a novel pathogenic TCTN3 variant: A case report and literature review.
PMID: 35170189
Am J Med Genet A Β· 2022
0.80
4
De novo heterozygous variants in SLC30A7 are a candidate cause for Joubert syndrome.
PMID: 35751429
Am J Med Genet A Β· 2022
0.70
5
A splice site variant in TCTN3 underlies an atypical form of orofaciodigital syndrome IV.
PMID: 36039988
Ann Hum Genet Β· 2022
0.60