TCTN2

tectonic family member 2, the group of MKS complex|Tectonic proteins

Basic information

Region (hg38): 12:123671110-123708399

Previous symbols: [ "C12orf38" ]

Links

ENSG00000168778 ∙ NCBI:79867 ∙ OMIM:613846 ∙ HGNC:25774 ∙ Uniprot:Q96GX1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 24 (Strong), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome 24 (Moderate), mode of inheritance: AR
• Joubert syndrome 24 (Strong), mode of inheritance: AR
• Joubert syndrome 24 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 24; Meckel syndrome 8	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	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal	20301500; 21462283; 21565611; 25118024
The conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveilMMABlance 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 TCTN2 gene.

• Joubert_syndrome (503 variants)
• Meckel-Gruber_syndrome (498 variants)
• Joubert_syndrome_24 (179 variants)
• Meckel_syndrome,_type_8 (176 variants)
• Inborn_genetic_diseases (111 variants)
• not_provided (97 variants)
• not_specified (27 variants)
• TCTN2-related_disorder (15 variants)
• Joubert_syndrome_and_related_disorders (5 variants)
• Meckel_syndrome,_type_6 (3 variants)
• Cutis_Laxa,_Recessive (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCTN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024809.5. 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			7	130	1	138
missense	1	6	284	13	1	305
nonsense	15	5	1			21
start loss						0
frameshift	12	18	2			32
splice donor/acceptor (+/-2bp)	1	18				19
Total	29	47	294	143	2

Highest pathogenic variant AF is 0.0000588627

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCTN2	protein_coding	protein_coding	ENST00000303372	18	37289

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.84e-14	0.556	125661	0	87	125748	0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.237	367	380	0.966	0.0000211	4550
Missense in Polyphen		68	78.949	0.86132		989
Synonymous	-0.655	161	151	1.07	0.00000962	1347
Loss of Function	1.60	27	37.6	0.718	0.00000192	430

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00123	0.00123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000361	0.000360
Middle Eastern	0.000163	0.000163
South Asian	0.000490	0.000457
Other	0.000165	0.000163

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. Required for hedgehog signaling transduction (By similarity). {ECO:0000250}.
• Disease: DISEASE: Meckel syndrome 8 (MKS8) [MIM:613885]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:21462283}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 24 (JBTS24) [MIM:616654]: 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, renal disease, liver fibrosis, and polydactyly. {ECO:0000269|PubMed:21565611, ECO:0000269|PubMed:25118024}. 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: 0.113
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.94

Haploinsufficiency Scores

• pHI: 0.0773
• hipred: N
• hipred_score: 0.233
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.115

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tctn2
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; vision/eye phenotype; limbs/digits/tail phenotype; 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); digestive/alimentary phenotype; growth/size/body region phenotype; cellular phenotype; craniofacial phenotype

Gene ontology

• Biological process: smoothened signaling pathway;cilium assembly;ciliary basal body-plasma membrane docking
• Cellular component: cytoplasm;cytoskeleton;integral component of membrane;MKS complex;ciliary membrane