Meckel syndrome, type 8

Summary

Meckel syndrome, type 8 (MONDO:0013482) is a disease caused by TCTN2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TCTN2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 207

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meckel syndrome, type 8
Mondo ID	MONDO:0013482
OMIM	613885
DOID	DOID:0070122
UMLS	C3836857
MedGen	854220
GARD	0015727
Is cancer (heuristic)	no

Also known as: Meckel syndrome caused by mutation in TCTN2 · Meckel syndrome, type 8 · MKS8 · TCTN2 Meckel syndrome

Data availability: 207 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Meckel syndrome › Meckel syndrome, type 8

Related subtypes (13): Meckel syndrome, type 1, NPHP3-related Meckel-like syndrome, Meckel syndrome, type 2, Meckel syndrome, type 3, Meckel syndrome, type 4, Meckel syndrome, type 5, Meckel syndrome, type 6, Meckel syndrome, type 10, Meckel syndrome, type 9, Meckel syndrome, type 11, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, meckel syndrome 14, Meckel syndrome 13

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

207 retrieved; paginated sample, class counts are floors:

129 uncertain significance, 29 conflicting classifications of pathogenicity, 15 likely pathogenic, 12 pathogenic/likely pathogenic, 11 benign, 8 benign/likely benign, 2 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
212387	NM_024809.5(TCTN2):c.134dup (p.Val46fs)	TCTN2	Pathogenic	criteria provided, single submitter
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
217701	NM_024809.5(TCTN2):c.76del (p.Asp26fs)	TCTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
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
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
3574362	NM_024809.5(TCTN2):c.1457_1458del (p.Ser486fs)	TCTN2	Likely pathogenic	criteria provided, single submitter
3574364	NM_024809.5(TCTN2):c.1545_1566dup (p.Asn523fs)	TCTN2	Likely pathogenic	criteria provided, single submitter
3574369	NM_024809.5(TCTN2):c.1612+1G>C	TCTN2	Likely pathogenic	criteria provided, single submitter
3574382	NM_024809.5(TCTN2):c.1911dup (p.Thr638fs)	TCTN2	Likely pathogenic	criteria provided, single submitter
4755455	NM_024809.5(TCTN2):c.71G>A (p.Trp24Ter)	TCTN2	Likely pathogenic	criteria provided, single submitter
1199799	NM_024809.5(TCTN2):c.271G>T (p.Val91Leu)	TCTN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
TCTN2	Strong	Autosomal recessive	Meckel syndrome, type 8	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCTN2	Orphanet:475	Isolated Joubert syndrome
TCTN2	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
TCTN2	HGNC:25774	ENSG00000168778	Q96GX1	Tectonic-2	gencc,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.

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)
TCTN2	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
buccal mucosa cell	1
olfactory bulb	1
tendon of biceps brachii	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TCTN2	1,254

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCTN2	Q96GX1	74.71

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	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to ciliary transition zone	1	2407.4×	0.001	TCTN2
smoothened signaling pathway	1	181.2×	0.008	TCTN2
cilium assembly	1	73.6×	0.014	TCTN2

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
TCTN2	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	TCTN2

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)
TCTN2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.