Joubert syndrome 13

Summary

Joubert syndrome 13 (MONDO:0013608) is a disease caused by TCTN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TCTN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 72

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 13
Mondo ID	MONDO:0013608
OMIM	614173
DOID	DOID:0110982
UMLS	C3280031
MedGen	481661
GARD	0015765
Is cancer (heuristic)	no

Also known as: JBTS13 · Joubert syndrome 13 · Joubert syndrome caused by mutation in TCTN1 · Joubert syndrome type 13 · TCTN1 Joubert syndrome

Data availability: 72 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 13

Related subtypes (38): Joubert syndrome 1, Joubert syndrome 10, Joubert syndrome 2, Joubert syndrome 3, Joubert syndrome with renal defect, Joubert syndrome 5, Joubert syndrome 6, Joubert syndrome 7, Joubert syndrome 9, Joubert syndrome 8, Joubert syndrome 14, Joubert syndrome 15, Joubert syndrome 16, Joubert syndrome 17, Joubert syndrome 18, Joubert syndrome 20, Joubert syndrome 21, Joubert syndrome 22, Joubert syndrome 23, Joubert syndrome 24, Joubert syndrome 25, Joubert syndrome 26, Joubert syndrome 27, Joubert syndrome 28, Joubert syndrome 38, Joubert syndrome 39, Joubert syndrome 40, Joubert syndrome 37, Joubert syndrome 35, Joubert syndrome 36, Joubert syndrome 30, Joubert syndrome 32, Joubert syndrome 31, Joubert syndrome 33, Joubert syndrome 19, Joubert syndrome 29, Joubert syndrome 11, Joubert syndrome 34

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

72 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 11 likely pathogenic, 10 pathogenic, 9 conflicting classifications of pathogenicity, 5 benign/likely benign, 3 pathogenic/likely pathogenic, 3 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1033279	NM_001082538.3(TCTN1):c.26_29dup (p.Val11fs)	TCTN1	Pathogenic	criteria provided, multiple submitters, no conflicts
1252090	NM_001082538.3(TCTN1):c.1385dup (p.Trp463fs)	TCTN1	Pathogenic	criteria provided, single submitter
1410963	NM_001082538.3(TCTN1):c.736A>T (p.Lys246Ter)	TCTN1	Pathogenic	criteria provided, multiple submitters, no conflicts
1451187	NM_001082538.3(TCTN1):c.411_412del (p.Arg138fs)	TCTN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805072	NM_001082538.3(TCTN1):c.378_381dup (p.Ser128fs)	TCTN1	Pathogenic	criteria provided, single submitter
183312	NM_001082538.3(TCTN1):c.342-2A>G	TCTN1	Pathogenic	criteria provided, multiple submitters, no conflicts
212386	NM_001082538.3(TCTN1):c.843+1del	TCTN1	Pathogenic	criteria provided, single submitter
221983	NM_001082538.3(TCTN1):c.898C>T (p.Arg300Ter)	TCTN1	Pathogenic	criteria provided, multiple submitters, no conflicts
265265	NM_001082538.3(TCTN1):c.978+1G>T	TCTN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30803	NM_001082538.3(TCTN1):c.221-2A>G	TCTN1	Pathogenic	criteria provided, single submitter
3574252	NM_001082538.3(TCTN1):c.1213_1216del (p.Asn405fs)	TCTN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4277234	NM_001082538.3(TCTN1):c.342-2A>C	TCTN1	Pathogenic	criteria provided, multiple submitters, no conflicts
829835	NM_001082538.3(TCTN1):c.1454G>A (p.Trp485Ter)	TCTN1	Pathogenic	no assertion criteria provided
1186116	NM_001082538.3(TCTN1):c.341+1G>A	TCTN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339906	NM_001082538.3(TCTN1):c.1494+1G>A	TCTN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1679957	NM_001082538.3(TCTN1):c.580del (p.Ser194fs)	TCTN1	Likely pathogenic	criteria provided, single submitter
3061949	NM_001082538.3(TCTN1):c.1635+1G>A	TCTN1	Likely pathogenic	criteria provided, single submitter
3339968	NM_001082538.3(TCTN1):c.342-8A>G	TCTN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3574250	NM_001082538.3(TCTN1):c.625-1G>A	TCTN1	Likely pathogenic	criteria provided, single submitter
3574251	NM_001082538.3(TCTN1):c.843+1G>A	TCTN1	Likely pathogenic	criteria provided, single submitter
3574253	NM_001082538.3(TCTN1):c.1274del (p.Glu425fs)	TCTN1	Likely pathogenic	criteria provided, single submitter
3574255	NM_001082538.3(TCTN1):c.1505del (p.Leu502fs)	TCTN1	Likely pathogenic	criteria provided, single submitter
3764639	NM_001082538.3(TCTN1):c.3G>C (p.Met1Ile)	TCTN1	Likely pathogenic	criteria provided, single submitter
4759234	NM_001082538.3(TCTN1):c.409C>T (p.Gln137Ter)	TCTN1	Likely pathogenic	criteria provided, single submitter
160100	NM_001082538.3(TCTN1):c.940G>A (p.Ala314Thr)	TCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194019	NM_001082538.3(TCTN1):c.1471A>T (p.Ile491Phe)	TCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198764	NM_001082538.3(TCTN1):c.934G>A (p.Val312Ile)	TCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
257400	NM_001082538.3(TCTN1):c.298G>A (p.Val100Met)	TCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
307208	NM_001082538.3(TCTN1):c.960C>T (p.Cys320=)	TCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
307209	NM_001082538.3(TCTN1):c.987C>T (p.Tyr329=)	TCTN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TCTN1	Strong	Autosomal recessive	Joubert syndrome 13	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCTN1	Orphanet:475	Isolated Joubert syndrome
TCTN1	Orphanet:564	Meckel syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCTN1	HGNC:26113	ENSG00000204852	Q2MV58	Tectonic-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCTN1	Tectonic-1	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCTN1	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCTN1	230	ubiquitous	marker	right uterine tube, adenohypophysis, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TCTN1	945

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCTN1	Q2MV58	78.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	TCTN1
Cilium Assembly	1	108.8×	0.014	TCTN1
Organelle biogenesis and maintenance	1	66.0×	0.015	TCTN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
central nervous system interneuron axonogenesis	1	16852.0×	5e-04	TCTN1
somatic motor neuron differentiation	1	5617.3×	8e-04	TCTN1
protein localization to ciliary transition zone	1	2407.4×	0.001	TCTN1
neural tube formation	1	2106.5×	0.001	TCTN1
telencephalon development	1	991.3×	0.002	TCTN1
dorsal/ventral neural tube patterning	1	802.5×	0.002	TCTN1
regulation of smoothened signaling pathway	1	624.1×	0.002	TCTN1
cilium assembly	1	73.6×	0.014	TCTN1
in utero embryonic development	1	72.0×	0.014	TCTN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TCTN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TCTN1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TCTN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.