TCTN2

Summary

TCTN2 (tectonic family member 2, HGNC:25774) is a protein-coding gene on chromosome 12q24.31, encoding Tectonic-2 (Q96GX1). 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.

This gene encodes a type I membrane protein that belongs to the tectonic family. Studies in mice suggest that this protein may be involved in hedgehog signaling, and essential for ciliogenesis. Mutations in this gene are associated with Meckel syndrome type 8. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79867 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 24 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 825 total — 31 pathogenic, 36 likely-pathogenic
• Phenotypes (HPO): 101
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_024809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25774
Approved symbol	TCTN2
Name	tectonic family member 2
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12975, TECT2, MKS8, JBTS24
Ensembl gene	ENSG00000168778
Ensembl biotype	protein_coding
OMIM	613846
Entrez	79867

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000303372, ENST00000426174, ENST00000541523, ENST00000543998, ENST00000679504, ENST00000680394, ENST00000680500, ENST00000680574, ENST00000864861, ENST00000965363, ENST00000965364

RefSeq mRNA: 3 — MANE Select: NM_024809 NM_001143850, NM_001410989, NM_024809

CCDS: CCDS45007, CCDS91766, CCDS9253

Canonical transcript exons

ENST00000303372 — 18 exons

Exon	Start	End
ENSE00001187662	123673615	123673810
ENSE00001212815	123671113	123671322
ENSE00001294060	123695220	123695297
ENSE00001297808	123690533	123690674
ENSE00001297851	123697087	123697198
ENSE00001304257	123686836	123687035
ENSE00001309584	123694842	123694976
ENSE00001313747	123696415	123696495
ENSE00001316304	123688051	123688177
ENSE00001320402	123692658	123692723
ENSE00001322753	123679189	123679289
ENSE00001328889	123706985	123707073
ENSE00001414645	123707604	123708399
ENSE00003608962	123699704	123699810
ENSE00003621066	123672056	123672132
ENSE00003626186	123706726	123706851
ENSE00003667559	123671507	123671614
ENSE00003685926	123704532	123704688

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9244 / max 82.1518, expressed in 1716 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128594	8.5774	1713
128595	0.2770	104
128596	0.0700	22

Top tissues by expression

265 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.65	gold quality
tendon of biceps brachii	UBERON:0008188	96.60	gold quality
olfactory bulb	UBERON:0002264	95.26	silver quality
type B pancreatic cell	CL:0000169	94.24	silver quality
right uterine tube	UBERON:0001302	93.91	gold quality
medial globus pallidus	UBERON:0002477	93.08	gold quality
globus pallidus	UBERON:0001875	91.21	gold quality
oviduct epithelium	UBERON:0004804	90.93	gold quality
nasal cavity epithelium	UBERON:0005384	90.30	silver quality
diaphragm	UBERON:0001103	89.74	silver quality
mucosa of urinary bladder	UBERON:0001259	89.53	gold quality
fallopian tube	UBERON:0003889	88.86	gold quality
oocyte	CL:0000023	88.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.02	gold quality
hair follicle	UBERON:0002073	86.95	gold quality
tendon	UBERON:0000043	85.59	gold quality
adenohypophysis	UBERON:0002196	85.53	gold quality
nephron tubule	UBERON:0001231	85.30	gold quality
epithelium of nasopharynx	UBERON:0001951	84.94	silver quality
ventricular zone	UBERON:0003053	84.94	gold quality
vena cava	UBERON:0004087	84.94	silver quality
pons	UBERON:0000988	84.73	gold quality
pituitary gland	UBERON:0000007	84.61	gold quality
substantia nigra pars compacta	UBERON:0001965	84.49	silver quality
mammary duct	UBERON:0001765	84.39	silver quality
metanephric glomerulus	UBERON:0004736	84.26	silver quality
stromal cell of endometrium	CL:0002255	84.13	gold quality
lateral globus pallidus	UBERON:0002476	84.13	silver quality
cervix squamous epithelium	UBERON:0006922	84.00	gold quality
secondary oocyte	CL:0000655	83.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting TCTN2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-5689	99.50	71.26	1154

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• a truncating mutation in TCTN2 linked to Meckel Gruber syndrome was shown. (PMID:21462283)
• Network building strategy led to the proposal of candidates for new ciliopathy disease genes, leading to the identification of the first human mutations in the Nephronophthisis gene Ataxin10 (ATXN10) and Joubert syndrome gene Tectonic2 (TCTN2). (PMID:21565611)
• TCTN2 Depletion-Induced IFT88 Lumen Leakage and Ciliary Weakening (PMID:29866362)
• Data suggest that TCTN2 enhances autophagy by targeting the miR-216b-Beclin-1 pathway, thereby ameliorating neuronal apoptosis and relieving spinal cord injury. (PMID:31050183)
• Two novel TCTN2 mutations cause Meckel-Gruber syndrome. (PMID:32655147)
• A founder mutation in TCTN2 causes Meckel-Gruber syndrome type 8 among Jews of Ethiopian and Yemenite origin. (PMID:33590725)
• LncRNA TCTN2 Promotes the Malignant Development of Hepatocellular Carcinoma via Regulating mIR-1285-3p/ARF6 Axis. (PMID:36278455)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tctn2	ENSDARG00000035633
mus_musculus	Tctn2	ENSMUSG00000118662
rattus_norvegicus	Tctn2	ENSRNOG00000088480
caenorhabditis_elegans		WBGENE00017120

Paralogs (2): TCTN3 (ENSG00000119977), TCTN1 (ENSG00000204852)

Protein

Protein identifiers

Tectonic-2 — Q96GX1 (reviewed: Q96GX1)

All UniProt accessions (5): Q96GX1, A0A7P0T886, A0A7P0T8X4, A0A7P0TAX5, F5H6G0

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Part of the tectonic-like complex (also named B9 complex).

Subcellular location. Membrane. Cytoplasm. Cytoskeleton. Cilium basal body.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the tectonic family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96GX1-1	1	yes
Q96GX1-2	2

RefSeq proteins (3): NP_001137322, NP_001397918, NP_079085* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011677	TCTN1-3_dom	Domain
IPR040354	TCTN1-3	Family
IPR057724	TCTN1-3_N	Domain

Pfam: PF07773, PF25752

UniProt features (10 total): glycosylation site 4, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GX1-F1	74.71	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (4): 146, 156, 391, 497

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly

MSigDB gene sets: 284 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, TTTGTAG_MIR520D, AMIT_SERUM_RESPONSE_40_MCF10A, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_SMOOTHENED_SIGNALING_PATHWAY, FISCHER_DREAM_TARGETS, RFX1_02, GOBP_CELL_PROJECTION_ORGANIZATION, CUI_TCF21_TARGETS_2_UP, GCCATNTTG_YY1_Q6, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_CILIARY_TRANSITION_ZONE, GOCC_PLASMA_MEMBRANE_REGION

GO Biological Process (4): smoothened signaling pathway (GO:0007224), cilium assembly (GO:0060271), protein localization to ciliary transition zone (GO:1904491), cell projection organization (GO:0030030)

GO Molecular Function (0):

GO Cellular Component (7): MKS complex (GO:0036038), ciliary membrane (GO:0060170), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), ciliary transition zone (GO:0035869), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein localization to cilium	2
cilium	2
cell surface receptor signaling pathway	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cellular component organization	1
protein-containing complex	1
ciliary transition zone	1
cell projection membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCTN2	B9D1	Q9UPM9	982
TCTN2	TCTN1	Q2MV58	975
TCTN2	CC2D2A	Q9P2K1	974
TCTN2	TMEM67	Q5HYA8	968
TCTN2	TMEM231	Q9H6L2	955
TCTN2	B9D2	Q9BPU9	949
TCTN2	TCTN3	Q6NUS6	938
TCTN2	MKS1	Q9NXB0	930
TCTN2	CEP290	O15078	925
TCTN2	TMEM216	Q9P0N5	905
TCTN2	RPGRIP1L	Q68CZ1	828
TCTN2	AHI1	Q8N157	822
TCTN2	TMEM237	Q96Q45	819
TCTN2	TMEM17	Q86X19	768
TCTN2	NPHP1	O15259	724

IntAct

56 interactions, top by confidence:

A	B	Type	Score
HLA-DRA	HLA-DRB1	psi-mi:“MI:0914”(association)	0.880
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
HLA-C	HLA-A	psi-mi:“MI:0914”(association)	0.670
TMEM231	TCTN1	psi-mi:“MI:0914”(association)	0.640
TCTN2	TCTN3	psi-mi:“MI:0914”(association)	0.640
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
OPRM1	TCTN2	psi-mi:“MI:0915”(physical association)	0.400
BTNL8	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-E	RTL8C	psi-mi:“MI:0914”(association)	0.350
PTPRK	MANBA	psi-mi:“MI:0914”(association)	0.350
TCTN1	PPOX	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350
TMEM231	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	FAM234B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
C1QA	MANBA	psi-mi:“MI:0914”(association)	0.350
DHFR2	MANBA	psi-mi:“MI:0914”(association)	0.350
DEFB135	MANBA	psi-mi:“MI:0914”(association)	0.350
DEFB109B	CHST10	psi-mi:“MI:0914”(association)	0.350
KLRC3	RNF13	psi-mi:“MI:0914”(association)	0.350

BioGRID (390): TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TCTN2 (Proximity Label-MS), AAAS (Proximity Label-MS), ABHD12 (Proximity Label-MS), ACSL3 (Proximity Label-MS), ADIPOR1 (Proximity Label-MS), ADIPOR2 (Proximity Label-MS)

ESM2 similar proteins: A1L2K1, A4FV27, A4IGL3, A4IH88, A8WFR0, A8WH34, L7VG99, O14525, O18638, O54715, O60486, O70367, O75829, O77770, P05300, P13473, P17046, P17047, P17404, P30120, P40682, P49130, Q14956, Q15904, Q2M385, Q5PPI4, Q5R5V2, Q5RBP9, Q61137, Q66K08, Q6AX53, Q6DDG2, Q6P7C7, Q7ZV46, Q8C0Z1, Q8VDA1, Q90617, Q96GX1, Q99P91, Q9D387

Diamond homologs: Q2MV57, Q3B7D3, Q96GX1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Interferon gamma signaling	6	17.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of T cell mediated cytotoxicity	5	44.8×	4e-05
ERAD pathway	5	15.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

825 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	36
Uncertain significance	348
Likely benign	267
Benign	62

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068960	NM_024809.5(TCTN2):c.573del (p.Ser192fs)	Pathogenic
1323682	NM_024809.5(TCTN2):c.1028T>G (p.Leu343Ter)	Pathogenic
1410878	NM_024809.5(TCTN2):c.1873_1874del (p.Gln625fs)	Pathogenic
1451983	NM_024809.5(TCTN2):c.1250_1251del (p.Arg417fs)	Pathogenic
189247	NM_024809.5(TCTN2):c.1877T>A (p.Leu626Ter)	Pathogenic
1953137	NM_024809.5(TCTN2):c.184G>T (p.Glu62Ter)	Pathogenic
2012732	NM_024809.5(TCTN2):c.1436T>G (p.Leu479Ter)	Pathogenic
2022718	NM_024809.5(TCTN2):c.1329del (p.Lys443fs)	Pathogenic
212387	NM_024809.5(TCTN2):c.134dup (p.Val46fs)	Pathogenic
2162181	NM_024809.5(TCTN2):c.487C>T (p.Gln163Ter)	Pathogenic
217699	NM_024809.5(TCTN2):c.1291G>T (p.Glu431Ter)	Pathogenic
217700	NM_024809.5(TCTN2):c.76dup (p.Asp26fs)	Pathogenic
2177127	NM_024809.5(TCTN2):c.1498del (p.Gln500fs)	Pathogenic
218099	NM_024809.5(TCTN2):c.1235-1G>A	Pathogenic
218100	NM_024809.5(TCTN2):c.1873C>T (p.Gln625Ter)	Pathogenic
2426893	NC_000012.11:g.(?124189059)(124192260_?)del	Pathogenic
2643516	NM_024809.5(TCTN2):c.83-2_96dup	Pathogenic
2927469	NM_024809.5(TCTN2):c.1743_1744delinsTT (p.Gln581_Gln582delinsHisTer)	Pathogenic
2942437	NM_024809.5(TCTN2):c.898del (p.Leu300fs)	Pathogenic
3381965	NM_024809.5(TCTN2):c.1141_1143delinsCAACCCCTAGAATTGT (p.Val381fs)	Pathogenic
3381966	NM_024809.5(TCTN2):c.1147G>T (p.Glu383Ter)	Pathogenic
3389965	NM_024809.5(TCTN2):c.1794C>G (p.Tyr598Ter)	Pathogenic
3760929	NM_024809.5(TCTN2):c.1385G>A (p.Trp462Ter)	Pathogenic
461767	NM_024809.5(TCTN2):c.652_659dup (p.Ala221fs)	Pathogenic
4787174	NM_024809.5(TCTN2):c.704dup (p.Cys236fs)	Pathogenic
4787571	NM_024809.5(TCTN2):c.191-2A>T	Pathogenic
4790384	NM_024809.5(TCTN2):c.721dup (p.Leu241fs)	Pathogenic
571826	NM_024809.5(TCTN2):c.367dup (p.Leu123fs)	Pathogenic
832383	NC_000012.12:g.(?123699684)(123699830_?)del	Pathogenic
917958	NM_024809.5(TCTN2):c.1852C>T (p.Gln618Ter)	Pathogenic

SpliceAI

2810 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123671605:G:GT	donor_gain	1.0000
12:123686834:A:AG	acceptor_gain	1.0000
12:123686835:G:GG	acceptor_gain	1.0000
12:123686835:GGA:G	acceptor_gain	1.0000
12:123687031:GCTGT:G	donor_gain	1.0000
12:123687034:GT:G	donor_gain	1.0000
12:123687036:G:GG	donor_gain	1.0000
12:123688049:A:AG	acceptor_gain	1.0000
12:123688050:G:GG	acceptor_gain	1.0000
12:123688050:GTTC:G	acceptor_gain	1.0000
12:123688050:GTTCC:G	acceptor_gain	1.0000
12:123688175:CAGGT:C	donor_loss	1.0000
12:123688176:AGG:A	donor_loss	1.0000
12:123688177:GG:G	donor_loss	1.0000
12:123688178:G:T	donor_loss	1.0000
12:123688179:T:C	donor_loss	1.0000
12:123692719:TACAG:T	donor_loss	1.0000
12:123692720:ACAG:A	donor_loss	1.0000
12:123692721:CAGGT:C	donor_loss	1.0000
12:123692722:AGGTA:A	donor_loss	1.0000
12:123692723:GG:G	donor_loss	1.0000
12:123692725:T:G	donor_loss	1.0000
12:123697085:A:AG	acceptor_gain	1.0000
12:123697085:AGCT:A	acceptor_gain	1.0000
12:123697086:G:GG	acceptor_gain	1.0000
12:123697086:GCTG:G	acceptor_gain	1.0000
12:123699698:TTGCA:T	acceptor_loss	1.0000
12:123699699:TGCAG:T	acceptor_loss	1.0000
12:123699700:GCAGG:G	acceptor_loss	1.0000
12:123699701:CA:C	acceptor_loss	1.0000

AlphaMissense

4556 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:123695249:T:C	F422L	0.988
12:123695251:T:A	F422L	0.988
12:123695251:T:G	F422L	0.988
12:123679242:T:A	C173S	0.987
12:123679243:G:C	C173S	0.987
12:123690575:T:C	F312L	0.985
12:123690577:T:A	F312L	0.985
12:123690577:T:G	F312L	0.985
12:123679275:T:C	C184R	0.984
12:123679236:T:C	C171R	0.983
12:123679242:T:C	C173R	0.983
12:123679275:T:A	C184S	0.982
12:123679276:G:C	C184S	0.982
12:123679243:G:A	C173Y	0.981
12:123690599:T:A	C320S	0.981
12:123690600:G:C	C320S	0.981
12:123679277:C:G	C184W	0.979
12:123671510:T:G	F29C	0.978
12:123690599:T:C	C320R	0.978
12:123673721:T:A	V125D	0.977
12:123679244:T:G	C173W	0.977
12:123679263:T:A	C180S	0.977
12:123679264:G:C	C180S	0.977
12:123671509:T:C	F29L	0.976
12:123671511:C:A	F29L	0.976
12:123671511:C:G	F29L	0.976
12:123686977:T:A	C236S	0.976
12:123686978:G:C	C236S	0.976
12:123679236:T:A	C171S	0.975
12:123679237:G:C	C171S	0.975

dbSNP variants (sampled 300 via entrez): RS1000067687 (12:123694133 A>C), RS1000083310 (12:123673507 T>C), RS1000124903 (12:123689268 G>A), RS1000149085 (12:123670539 A>T), RS1000201859 (12:123670194 AATAAATAT>A), RS1000278759 (12:123702117 T>C), RS1000302041 (12:123676156 T>C), RS1000382329 (12:123708875 C>T), RS1000440298 (12:123702377 C>T), RS1000465066 (12:123682468 GT>G), RS1000518461 (12:123683504 C>A,T), RS1000573976 (12:123695970 A>G), RS1000614521 (12:123700683 G>A), RS1000682951 (12:123705767 T>G), RS1000756442 (12:123675931 A>G)

Disease associations

OMIM: gene MIM:613846 | disease phenotypes: MIM:213300, MIM:249000, MIM:613885, MIM:616654, MIM:608776, MIM:612284

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 24	Strong	Autosomal recessive
Meckel syndrome, type 8	Strong	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive
Meckel syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Joubert syndrome 24	Definitive	AR

Mondo (9): Joubert syndrome (MONDO:0018772), Meckel syndrome (MONDO:0018921), Meckel syndrome, type 8 (MONDO:0013482), Joubert syndrome 24 (MONDO:0014724), Joubert syndrome and related disorders (MONDO:0015369), ALG9-congenital disorder of glycosylation (MONDO:0012117), microcephaly (MONDO:0001149), Meckel syndrome, type 6 (MONDO:0012848), focal segmental glomerulosclerosis (MONDO:0100313)

Orphanet (4): Isolated Joubert syndrome (Orphanet:475), Meckel syndrome (Orphanet:564), Joubert syndrome and related disorders (Orphanet:140874), ALG9-CDG (Orphanet:79328)

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000037	Male pseudohermaphroditism
HP:0000062	Ambiguous genitalia
HP:0000068	Urethral atresia
HP:0000073	Ureteral duplication
HP:0000105	Enlarged kidney
HP:0000113	Polycystic kidney dysplasia
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000508	Ptosis

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005956_10	Waist-to-hip ratio adjusted for BMI	6.000000e-08
GCST005958_11	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-07
GCST005962_22	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST90013406_254	Liver enzyme levels (alkaline phosphatase)	1.000000e-16
GCST90020025_59	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020027_1234	Waist-hip index	7.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C535750	Congenital disorder of glycosylation type 1L (supp.)
C567365	Meckel Syndrome, Type 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Lead	increases expression	1
Smoke	increases abundance, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

96 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT01164098	PHASE3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	PHASE3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	PHASE3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	PHASE3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	PHASE3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
NCT00550342	PHASE2	WITHDRAWN	Rituximab Treatment of Focal Segmental Glomerulosclerosis
NCT00814255	PHASE2	COMPLETED	Novel Therapies for Resistant FSGS (FONTII): Phase II Clinical Trial
NCT01613118	PHASE2	COMPLETED	Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis
NCT02592798	PHASE2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT03366337	PHASE2	COMPLETED	A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX
NCT03448692	PHASE2	TERMINATED	A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT03536754	PHASE2	COMPLETED	A Study of CCX140-B in Subjects With FSGS
NCT03598036	PHASE2	TERMINATED	Dose-Exploration Evaluating the Efficacy and Safety of Voclosporin in Subjects With Focal Segmental Glomerulosclerosis
NCT03649152	PHASE2	COMPLETED	Safety and Effectiveness of Propagermanium in Focal Segmental Glomerulosclerosis Participants Receiving Irbesartan
NCT03703908	PHASE2	TERMINATED	A Study of CCX140-B in Subjects With Primary FSGS and Nephrotic Syndrome
NCT04009668	PHASE2	COMPLETED	Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
NCT04573920	PHASE2	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With Proteinuric Glomerular Diseases
NCT05003986	PHASE2	RECRUITING	Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases
NCT05267262	PHASE2	COMPLETED	Study to Evaluate R3R01 in Patients With Alport Syndrome and Patients With Focal Segmental Glomerulosclerosis
NCT05441826	PHASE2	TERMINATED	Efficacy and Safety of VB119 in Subjects With Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS)
NCT06500702	PHASE2	RECRUITING	A Study to Evaluate the Efficacy and Safety of Frexalimab, Brivekimig, or Rilzabrutinib in Participants Aged 16 to 75 Years With Primary Focal Segmental Glomerulosclerosis or Minimal Change Disease
NCT06664814	PHASE2	RECRUITING	An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Primary Focal Segmental Glomerulosclerosis
NCT06983028	PHASE2	RECRUITING	Atacicept in Multiple Glomerular Diseases
NCT07268638	PHASE2	RECRUITING	A Study of Praliciguat in Participants With Focal Segmental Glomerulosclerosis (FSGS)
NCT07614477	PHASE2	RECRUITING	Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of EVER001 in Participants With Selected Proteinuric Glomerular Diseases
NCT00464321	PHASE1	COMPLETED	Safety Study of GC1008 in Patients With Focal Segmental Glomerulosclerosis (FSGS) of Single Doses of GC1008 in Patients With Treatment Resistant Idiopathic FSGS
NCT00782561	PHASE1	TERMINATED	Safety and Pharmacokinetics of FG-3019 in Adolescents and Adults With Focal Segmental Glomerulosclerosis (FSGS)
NCT00816478	PHASE1	TERMINATED	Effect of Oral Galactose on Focal Segmental Glomerulosclerosis (FSGS) Permeability Factor
NCT00816504	PHASE1	WITHDRAWN	Effect of Galactose on Permeblity Factor in Patients With FSGS and CKD Stage 5
NCT02382874	PHASE1	UNKNOWN	Allogenic AD-MSC Transplantation in Idiopathic Nephrotic Syndrome (Focal Segmental Glomerulosclerosis)
NCT02693366	PHASE1	COMPLETED	Stem Cell Therapy for Patients With Focal Segmental Glomerulosclerosis
NCT05942625	PHASE1	RECRUITING	A First in Human Study to Evaluate Safety, Tolerability, Pharmacology of HS-10390 in Healthy Subjects
NCT05955872	PHASE1	COMPLETED	A Study Evaluating the Relative Bioavailability and Food Effect of a Tablet Formulation of VX-147
NCT06529796	PHASE1	COMPLETED	Evaluation of the Pharmacokinetics and Safety of Inaxaplin in Participants With Mild or Moderate Hepatic Impairment