TCTN3

tectonic family member 3, the group of Tectonic proteins

Basic information

Region (hg38): 10:95659823-95694143

Previous symbols: [ "C10orf61" ]

Links

ENSG00000119977 ∙ NCBI:26123 ∙ OMIM:613847 ∙ HGNC:24519 ∙ Uniprot:Q6NUS6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orofaciodigital syndrome IV (Definitive), mode of inheritance: AR
• orofaciodigital syndrome IV (Strong), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• orofaciodigital syndrome IV (Supportive), mode of inheritance: AR
• orofaciodigital syndrome type 6 (Supportive), mode of inheritance: AR
• Joubert syndrome 18 (Strong), mode of inheritance: AR
• orofaciodigital syndrome IV (Strong), mode of inheritance: AR
• ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 18; Orofaciodigital syndrome IV (Mohr-Majewski syndrome)	AR	Cardiovascular	The condition can include congenital cardiac anomalies, and awareness may allow early identification and management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	22883145
The condition can include cardiac, renal, and other manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCTN3 gene.

• Joubert_syndrome_18 (452 variants)
• Orofacial-digital_syndrome_IV (452 variants)
• Inborn_genetic_diseases (76 variants)
• not_provided (70 variants)
• not_specified (26 variants)
• TCTN3-related_disorder (14 variants)
• Joubert_syndrome_and_related_disorders (8 variants)
• Ciliopathy (2 variants)
• Long_QT_syndrome (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCTN3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015631.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	123	2	130
missense	1		215	9	1	226
nonsense	4	7	3	1		15
start loss	2	3				5
frameshift	23	11	8			42
splice donor/acceptor (+/-2bp)	2	12				14
Total	32	33	231	133	3

Highest pathogenic variant AF is 0.00019660068

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCTN3	protein_coding	protein_coding	ENST00000371217	14	30743

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.15e-12	0.526	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.836	273	315	0.867	0.0000144	3936
Missense in Polyphen		63	79.309	0.79436		1064
Synonymous	0.382	115	120	0.956	0.00000570	1219
Loss of Function	1.38	22	30.2	0.728	0.00000135	352

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000389	0.000388
Ashkenazi Jewish	0.00	0.00
East Asian	0.000545	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.000545	0.000544
South Asian	0.000360	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (By similarity). May be involved in apoptosis regulation. Necessary for signal transduction through the sonic hedgehog (Shh) signaling pathway. {ECO:0000250, ECO:0000269|PubMed:17464193, ECO:0000269|PubMed:22883145}.
• Disease: DISEASE: Orofaciodigital syndrome 4 (OFD4) [MIM:258860]: A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD4 patients have tongue nodules, multiple frenulae, broad flat nose, hypertelorism, and short rib polydactyly with tibial dysplasia (Majewski syndrome). The presence of severe tibial aplasia differentiates OFD4 from OFD1. Additional features of cystic dysplastic kidneys and brain malformation, including occipital encephalocele, are observed in severely affected patients. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 18 (JBTS18) [MIM:614815]: A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. JBTS18 patients have vermis agenesis and the molar tooth sign as well as severe kyphoscoliosis. Other features include intrauterine growth retardation, oral anomalies, micrognathism, polydactyly and camptodactyly, joint laxity, horseshoe kidney, and ventricular septal defect. {ECO:0000269|PubMed:22883145}. Note=The disease is caused by mutations affecting the gene represented in this entry. TCTN3-mutated fibroblasts from JBTS18 patients fail to respond to Shh agonists suggesting that at least some of the defects in affected individuals may be secondary to reduced Shh signaling (PubMed:22883145). {ECO:0000269|PubMed:22883145}.
• Pathway: Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0867

Intolerance Scores

• loftool: 0.223
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.46

Haploinsufficiency Scores

• pHI: 0.138
• hipred: N
• hipred_score: 0.123
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.141

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tctn3

Gene ontology

• Biological process: apoptotic process;smoothened signaling pathway;positive regulation of apoptotic process;cilium assembly;ciliary basal body-plasma membrane docking
• Cellular component: nucleus;integral component of membrane;ciliary membrane