TCTN1

tectonic family member 1, the group of Tectonic proteins|MKS complex

Basic information

Region (hg38): 12:110614026-110663431

Links

ENSG00000204852 ∙ NCBI:79600 ∙ OMIM:609863 ∙ HGNC:26113 ∙ Uniprot:Q2MV58 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 13 (Strong), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome 13 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 13	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	20301500; 21725307; 26477546
The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCTN1 gene.

• Meckel-Gruber syndrome;Familial aplasia of the vermis (155 variants)
• Familial aplasia of the vermis;Meckel-Gruber syndrome (137 variants)
• not provided (75 variants)
• Joubert syndrome 13 (51 variants)
• Inborn genetic diseases (24 variants)
• not specified (21 variants)
• Joubert syndrome and related disorders (4 variants)
• TCTN1-related condition (3 variants)
• Developmental disorder (2 variants)
• Familial aplasia of the vermis (1 variants)
• Typical Joubert syndrome MRI findings;Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCTN1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	78	1	83
missense		1	140	5	1	147
nonsense	2	1				3
start loss						0
frameshift	8	3	1			12
inframe indel			6			6
splice donor/acceptor (+/-2bp)	4	10				14
splice region			4	6	2	12
non coding			7	56	18	81
Total	14	15	158	139	20

Highest pathogenic variant AF is 0.0000592

Variants in TCTN1

This is a list of pathogenic ClinVar variants found in the TCTN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-110614043-A-G		Joubert syndrome 13	Uncertain significance (Jan 13, 2018)
12-110614099-T-C		Joubert syndrome 13	Uncertain significance (Jan 12, 2018)
12-110614137-G-C		Joubert syndrome 13 • not specified	Likely benign (Jan 12, 2018)
12-110614164-C-A		not specified	Likely benign (-)
12-110614169-G-A		Joubert syndrome 13	Conflicting classifications of pathogenicity (Apr 09, 2018)
12-110614175-C-T		not specified	Likely benign (-)
12-110614190-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Sep 06, 2022)
12-110614191-G-T			Likely benign (Oct 16, 2018)
12-110614196-G-A		Joubert syndrome 13 • Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Jul 12, 2022)
12-110614200-C-G		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Sep 12, 2022)
12-110614201-C-T		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Nov 01, 2022)
12-110614203-G-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Aug 01, 2023)
12-110614205-CGCTCCTGGTGGT-C		not specified • Joubert syndrome 13	Uncertain significance (Feb 21, 2023)
12-110614206-G-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Oct 25, 2021)
12-110614207-C-CTCCT		Joubert syndrome 13	Pathogenic (Feb 01, 2018)
12-110614219-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Dec 26, 2020)
12-110614221-C-G		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Sep 19, 2022)
12-110614236-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Nov 06, 2023)
12-110614239-C-T		Meckel-Gruber syndrome;Familial aplasia of the vermis	Likely benign (Nov 07, 2023)
12-110614247-C-T		Inborn genetic diseases	Uncertain significance (May 03, 2023)
12-110614265-C-T		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Oct 27, 2020)
12-110614266-G-A		Familial aplasia of the vermis;Meckel-Gruber syndrome	Likely benign (Nov 08, 2022)
12-110614266-G-C		Familial aplasia of the vermis;Meckel-Gruber syndrome	Likely benign (Oct 16, 2022)
12-110614295-C-G		Familial aplasia of the vermis;Meckel-Gruber syndrome	Uncertain significance (Oct 05, 2021)
12-110614296-C-A		Meckel-Gruber syndrome;Familial aplasia of the vermis	Uncertain significance (Feb 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCTN1	protein_coding	protein_coding	ENST00000397659	14	35404

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.07e-15	0.0385	124707	0	89	124796	0.000357

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.606	282	312	0.904	0.0000165	3816
Missense in Polyphen		80	92.265	0.86707		1224
Synonymous	1.32	110	129	0.852	0.00000783	1224
Loss of Function	0.579	25	28.3	0.883	0.00000141	325

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000597	0.000584
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000223
Finnish	0.000471	0.000464
European (Non-Finnish)	0.000467	0.000441
Middle Eastern	0.000223	0.000223
South Asian	0.000490	0.000294
Other	0.000338	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. Regulator of Hedgehog (Hh), required for both activation and inhibition of the Hh pathway in the patterning of the neural tube. During neural tube development, it is required for formation of the most ventral cell types and for full Hh pathway activation. Functions in Hh signal transduction to fully activate the pathway in the presence of high Hh levels and to repress the pathway in the absence of Hh signals. Modulates Hh signal transduction downstream of SMO and RAB23 (By similarity). {ECO:0000250}.
• Disease: DISEASE: Joubert syndrome 13 (JBTS13) [MIM:614173]: 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. {ECO:0000269|PubMed:21725307}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Intolerance Scores

• loftool: 0.263
• rvis_EVS: 0.18
• rvis_percentile_EVS: 66.07

Haploinsufficiency Scores

• pHI: 0.144
• hipred: N
• hipred_score: 0.123
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0148

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tctn1
• Phenotype: cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; embryo phenotype

Gene ontology

• Biological process: in utero embryonic development;neural tube formation;regulation of smoothened signaling pathway;somatic motor neuron differentiation;telencephalon development;dorsal/ventral neural tube patterning;central nervous system interneuron axonogenesis;cilium assembly;ciliary basal body-plasma membrane docking;protein localization to ciliary transition zone
• Cellular component: extracellular space;cytosol;cytoskeleton;membrane;MKS complex