Joubert syndrome 24

Summary

Joubert syndrome 24 (MONDO:0014724) is a disease caused by TCTN2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TCTN2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 210

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 24
Mondo ID	MONDO:0014724
OMIM	616654
DOID	DOID:0110993
UMLS	C4084841
MedGen	905319
GARD	0016150
Is cancer (heuristic)	no

Also known as: JBTS24 · Joubert syndrome 24 · Joubert syndrome caused by mutation in TCTN2 · Joubert syndrome type 24 · TCTN2 Joubert syndrome

Data availability: 210 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 24

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 13, 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 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

210 retrieved; paginated sample, class counts are floors:

128 uncertain significance, 28 conflicting classifications of pathogenicity, 15 likely pathogenic, 13 pathogenic/likely pathogenic, 11 benign, 8 benign/likely benign, 6 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1207911	NM_024809.5(TCTN2):c.1336C>T (p.Arg446Ter)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1381521	NM_024809.5(TCTN2):c.1888_1889del (p.Leu630fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1932648	NM_024809.5(TCTN2):c.1317C>G (p.Tyr439Ter)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212389	NM_024809.5(TCTN2):c.703del (p.Leu235fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217697	NM_024809.5(TCTN2):c.1626del (p.Asp543fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217700	NM_024809.5(TCTN2):c.76dup (p.Asp26fs)	TCTN2	Pathogenic	criteria provided, single submitter
217701	NM_024809.5(TCTN2):c.76del (p.Asp26fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218099	NM_024809.5(TCTN2):c.1235-1G>A	TCTN2	Pathogenic	no assertion criteria provided
218100	NM_024809.5(TCTN2):c.1873C>T (p.Gln625Ter)	TCTN2	Pathogenic	criteria provided, single submitter
2691565	NM_024809.5(TCTN2):c.1806dup (p.Thr603fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3064004	NM_024809.5(TCTN2):c.1550dup (p.His517fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31076	NM_024809.5(TCTN2):c.1506-2A>G	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3381965	NM_024809.5(TCTN2):c.1141_1143delinsCAACCCCTAGAATTGT (p.Val381fs)	TCTN2	Pathogenic	criteria provided, single submitter
3381966	NM_024809.5(TCTN2):c.1147G>T (p.Glu383Ter)	TCTN2	Pathogenic	criteria provided, single submitter
3574349	NM_024809.5(TCTN2):c.916C>T (p.Gln306Ter)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3574376	NM_024809.5(TCTN2):c.1788G>A (p.Trp596Ter)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
461766	NM_024809.5(TCTN2):c.524dup (p.Leu175fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
917958	NM_024809.5(TCTN2):c.1852C>T (p.Gln618Ter)	TCTN2	Pathogenic	criteria provided, single submitter
931914	NM_024809.5(TCTN2):c.988C>T (p.Arg330Ter)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1483923	NM_024809.5(TCTN2):c.1612+1G>A	TCTN2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1500877	NM_024809.5(TCTN2):c.267+1G>A	TCTN2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2141508	NM_024809.5(TCTN2):c.565-1G>A	TCTN2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2412723	NM_024809.5(TCTN2):c.1877dup (p.Leu626fs)	TCTN2	Likely pathogenic	criteria provided, single submitter
2927895	NM_024809.5(TCTN2):c.765-1G>C	TCTN2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3574331	NM_024809.5(TCTN2):c.83-1G>A	TCTN2	Likely pathogenic	criteria provided, single submitter
3574333	NM_024809.5(TCTN2):c.190+1del	TCTN2	Likely pathogenic	criteria provided, single submitter
3574339	NM_024809.5(TCTN2):c.311G>A (p.Trp104Ter)	TCTN2	Likely pathogenic	criteria provided, single submitter
3574346	NM_024809.5(TCTN2):c.764+2T>C	TCTN2	Likely pathogenic	criteria provided, single submitter
3574356	NM_024809.5(TCTN2):c.1246_1247del (p.Gln416fs)	TCTN2	Likely pathogenic	criteria provided, single submitter
3574357	NM_024809.5(TCTN2):c.1263del (p.Lys421fs)	TCTN2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · 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
TCTN2	Strong	Autosomal recessive	Joubert syndrome 24	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCTN2	Orphanet:475	Isolated Joubert syndrome
TCTN2	Orphanet:564	Meckel syndrome
LMOD3	Orphanet:171430	Severe congenital nemaline myopathy
LMOD3	Orphanet:171436	Typical nemaline myopathy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCTN2	HGNC:25774	ENSG00000168778	Q96GX1	Tectonic-2	gencc,clinvar
LMOD3	HGNC:6649	ENSG00000163380	Q0VAK6	Leiomodin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCTN2	Tectonic-2	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.
LMOD3	Leiomodin-3	Essential for the organization of sarcomeric actin thin filaments in skeletal muscle.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCTN2	Other/Unknown	no		TCTN1-3_dom, TCTN1-3, TCTN1-3_N
LMOD3	Other/Unknown	no		TMOD, LRR_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
olfactory bulb	1
tendon of biceps brachii	1
biceps brachii	1
quadriceps femoris	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCTN2	218	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, olfactory bulb
LMOD3	170	tissue_specific	marker	biceps brachii, vastus lateralis, quadriceps femoris

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TCTN2	1,254
LMOD3	838

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCTN2	Q96GX1	74.71
LMOD3	Q0VAK6	67.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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	TCTN2
Cilium Assembly	1	108.8×	0.014	TCTN2
Organelle biogenesis and maintenance	1	66.0×	0.015	TCTN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skeletal muscle thin filament assembly	1	1404.3×	0.003	LMOD3
pointed-end actin filament capping	1	1203.7×	0.003	LMOD3
protein localization to ciliary transition zone	1	1203.7×	0.003	TCTN2
positive regulation of skeletal muscle fiber development	1	1053.2×	0.003	LMOD3
actin nucleation	1	936.2×	0.003	LMOD3
myofibril assembly	1	561.7×	0.004	LMOD3
striated muscle contraction	1	421.3×	0.004	LMOD3
skeletal muscle fiber development	1	271.8×	0.006	LMOD3
muscle contraction	1	104.0×	0.013	LMOD3
smoothened signaling pathway	1	90.6×	0.013	TCTN2
actin filament organization	1	59.3×	0.018	LMOD3
cilium assembly	1	36.8×	0.027	TCTN2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
TCTN2	0	0
LMOD3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	TCTN2, LMOD3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TCTN2	0	—
LMOD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.