TCTN1

Summary

TCTN1 (tectonic family member 1, HGNC:26113) is a protein-coding gene on chromosome 12q24.11, encoding Tectonic-1 (Q2MV58). 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 member of a family of secreted and transmembrane proteins. The orthologous gene in mouse functions downstream of smoothened and rab23 to modulate hedgehog signal transduction. This protein is a component of the tectonic-like complex, which forms a barrier between the ciliary axoneme and the basal body. A mutation in this gene was found in a family with Joubert syndrome-13. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79600 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 13 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 505 total — 33 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 80
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001082538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26113
Approved symbol	TCTN1
Name	tectonic family member 1
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21127, TECT1, JBTS13
Ensembl gene	ENSG00000204852
Ensembl biotype	protein_coding
OMIM	609863
Entrez	79600

Gene structure

Transcript identifiers

Ensembl transcripts: 81 — 44 protein_coding, 23 nonsense_mediated_decay, 13 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000377654, ENST00000397655, ENST00000397656, ENST00000397659, ENST00000460357, ENST00000463313, ENST00000464809, ENST00000471804, ENST00000478122, ENST00000480648, ENST00000481093, ENST00000481720, ENST00000482281, ENST00000485445, ENST00000490514, ENST00000491068, ENST00000495659, ENST00000498072, ENST00000546643, ENST00000547461, ENST00000547868, ENST00000549123, ENST00000550703, ENST00000551555, ENST00000551590, ENST00000552038, ENST00000552318, ENST00000552762, ENST00000614115, ENST00000679401, ENST00000679473, ENST00000679617, ENST00000679713, ENST00000680068, ENST00000680168, ENST00000680203, ENST00000680445, ENST00000680512, ENST00000680548, ENST00000680571, ENST00000681395, ENST00000681437, ENST00000681604, ENST00000681703, ENST00000681740, ENST00000681807, ENST00000681851, ENST00000889000, ENST00000889001, ENST00000889002, ENST00000889003, ENST00000889004, ENST00000889005, ENST00000889006, ENST00000889007, ENST00000889008, ENST00000889009, ENST00000889010, ENST00000889011, ENST00000889012, ENST00000889013, ENST00000889014, ENST00000889015, ENST00000889016, ENST00000889017, ENST00000889018, ENST00000889019, ENST00000889020, ENST00000889021, ENST00000889022, ENST00000934350, ENST00000949050, ENST00000949051, ENST00000949052, ENST00000949053, ENST00000949054, ENST00000949055, ENST00000949056, ENST00000949057, ENST00000949058, ENST00000949059

RefSeq mRNA: 8 — MANE Select: NM_001082538 NM_001082537, NM_001082538, NM_001173975, NM_001173976, NM_001319680, NM_001319681, NM_001319682, NM_024549

CCDS: CCDS41833, CCDS41834, CCDS41835, CCDS91749

Canonical transcript exons

ENST00000397659 — 15 exons

Exon	Start	End
ENSE00001829401	110614129	110614402
ENSE00002378299	110649043	110649430
ENSE00003462778	110636481	110636501
ENSE00003463221	110640383	110640517
ENSE00003506109	110632472	110632559
ENSE00003546987	110647749	110647893
ENSE00003549201	110641542	110641627
ENSE00003553288	110641024	110641149
ENSE00003592438	110644967	110645129
ENSE00003635688	110647196	110647336
ENSE00003659257	110634670	110634779
ENSE00003661350	110619836	110619956
ENSE00003686984	110642249	110642389
ENSE00003689626	110626362	110626492
ENSE00003743415	110628767	110628918

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2924 / max 333.3522, expressed in 1775 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128004	22.1586	1772
128003	1.0897	731
128005	1.0440	635

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.58	gold quality
adenohypophysis	UBERON:0002196	96.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.32	gold quality
pituitary gland	UBERON:0000007	95.28	gold quality
ventricular zone	UBERON:0003053	95.02	gold quality
right lobe of thyroid gland	UBERON:0001119	95.00	gold quality
left lobe of thyroid gland	UBERON:0001120	94.94	gold quality
bronchial epithelial cell	CL:0002328	94.76	gold quality
right testis	UBERON:0004534	94.73	gold quality
thyroid gland	UBERON:0002046	94.44	gold quality
left testis	UBERON:0004533	94.19	gold quality
epithelium of bronchus	UBERON:0002031	93.88	gold quality
right ovary	UBERON:0002118	93.58	gold quality
left ovary	UBERON:0002119	93.42	gold quality
bronchus	UBERON:0002185	93.04	gold quality
stromal cell of endometrium	CL:0002255	92.40	gold quality
metanephros cortex	UBERON:0010533	92.32	gold quality
endocervix	UBERON:0000458	91.90	gold quality
testis	UBERON:0000473	91.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.74	gold quality
right adrenal gland cortex	UBERON:0035827	91.66	gold quality
body of uterus	UBERON:0009853	91.54	gold quality
gall bladder	UBERON:0002110	91.52	gold quality
right coronary artery	UBERON:0001625	91.42	gold quality
right atrium auricular region	UBERON:0006631	91.24	gold quality
right adrenal gland	UBERON:0001233	91.22	gold quality
left adrenal gland cortex	UBERON:0035825	91.10	gold quality
ovary	UBERON:0000992	91.06	gold quality
left uterine tube	UBERON:0001303	90.88	gold quality
left adrenal gland	UBERON:0001234	90.64	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	10.76
E-ANND-3	yes	7.38
E-GEOD-86618	no	48.86

Regulation

Is transcription factor: no

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 9)

• Mutations in Tctn1 is associated with ciliopathies. (PMID:21725307)
• TCTN1 may serve as a novel prognostic factor and a potential therapeutic target for glioblastoma. (PMID:25304031)
• These data suggest TCTN1 is essential for glioma cell viability, and dysregulation of TCTN1 may play a key role in glioma tumorigenesis. (PMID:25737023)
• These findings confirmed the direct association between the TCTN1 gene and prostate cancer growth in vitro. (PMID:26310786)
• Flow cytometry analysis showed that depletion of TCTN1 could cause cell cycle arrest at the G2/M phase. This indicates that TCTN1 may be crucial for CRC cell growth. (PMID:28123172)
• we describe the phenotype of a patient with Varadi syndrome who is homozygous for a previously reported mutation in TCTN1 (NM_001082538.2:c.342-2A>G, p.Gly115Lysfs*8) and suggest that allelic disorders linked to TCTN1 include Varadi syndrome, in addition to Joubert syndrome and Meckel-Gruber syndrome. (PMID:28631893)
• Two novel TCTN1 mutations were identified in a family with Joubert syndrome (PMID:31302911)
• microRNA-216a-5p inhibits the development of gastric cancer through target combination with TCTN1. (PMID:32486612)
• Function and transcriptional regulation of TCTN1 in oral squamous cell carcinoma. (PMID:34859261)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tctn1	ENSDARG00000078447
mus_musculus	Tctn1	ENSMUSG00000038593
rattus_norvegicus	Tctn1	ENSRNOG00000028523
caenorhabditis_elegans		WBGENE00017120

Paralogs (2): TCTN3 (ENSG00000119977), TCTN2 (ENSG00000168778)

Protein

Protein identifiers

Tectonic-1 — Q2MV58 (reviewed: Q2MV58)

All UniProt accessions (19): A0A087X1J4, A0A0A0MRU7, A0A7P0T8M6, A0A7P0T8R0, A0A7P0T9A6, A0A7P0TA68, A0A7P0TAW1, B4DIB9, E9PIB8, E9PNE4, E9PR69, Q2MV58, F8VQ12, F8VSB8, J3KPW2, S4R2Y1, S4R339, S4R3G2, S4R3M8

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. Regulator of Hedgehog (Hh), required for both activation and inhibition of the Hh pathway in the patterning of the neural tube. During neural tube development, it is required for formation of the most ventral cell types and for full Hh pathway activation. Functions in Hh signal transduction to fully activate the pathway in the presence of high Hh levels and to repress the pathway in the absence of Hh signals. Modulates Hh signal transduction downstream of SMO and RAB23.

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

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

Disease relevance. Joubert syndrome 13 (JBTS13) [MIM:614173] 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 and renal disease. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the tectonic family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q2MV58-1	1	yes
Q2MV58-2	2
Q2MV58-3	3
Q2MV58-4	4
Q2MV58-5	5
Q2MV58-6	6

RefSeq proteins (8): NP_001076006, NP_001076007, NP_001167446, NP_001167447, NP_001306609, NP_001306610, NP_001306611, NP_078825 (=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 (18 total): splice variant 8, sequence conflict 3, glycosylation site 3, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2MV58-F1	78.10	0.37

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 (3): 36, 295, 528

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: 310 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_SPINAL_CORD_MOTOR_NEURON_DIFFERENTIATION, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT, MODULE_205, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT

GO Biological Process (10): in utero embryonic development (GO:0001701), neural tube formation (GO:0001841), regulation of smoothened signaling pathway (GO:0008589), somatic motor neuron differentiation (GO:0021523), telencephalon development (GO:0021537), dorsal/ventral neural tube patterning (GO:0021904), central nervous system interneuron axonogenesis (GO:0021956), cilium assembly (GO:0060271), protein localization to ciliary transition zone (GO:1904491), cell projection organization (GO:0030030)

GO Molecular Function (0):

GO Cellular Component (9): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), membrane (GO:0016020), MKS complex (GO:0036038), extracellular region (GO:0005576), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), 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	6
protein localization to cilium	2
chordate embryonic development	1
embryonic epithelial tube formation	1
neural tube development	1
smoothened signaling pathway	1
regulation of signal transduction	1
spinal cord motor neuron differentiation	1
forebrain development	1
anatomical structure development	1
dorsal/ventral pattern formation	1
neural tube patterning	1
central nervous system neuron axonogenesis	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
cytoplasm	1
protein-containing complex	1
ciliary transition zone	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cilium	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCTN1	B9D1	Q9UPM9	991
TCTN1	MKS1	Q9NXB0	987
TCTN1	CC2D2A	Q9P2K1	981
TCTN1	TMEM216	Q9P0N5	976
TCTN1	TCTN2	Q96GX1	975
TCTN1	TMEM67	Q5HYA8	968
TCTN1	TMEM231	Q9H6L2	964
TCTN1	TCTN3	Q6NUS6	960
TCTN1	B9D2	Q9BPU9	953
TCTN1	CEP290	O15078	946
TCTN1	AHI1	Q8N157	896
TCTN1	TMEM237	Q96Q45	862
TCTN1	NPHP1	O15259	830
TCTN1	TMEM17	Q86X19	823
TCTN1	RPGRIP1L	Q68CZ1	803

IntAct

28 interactions, top by confidence:

A	B	Type	Score
TMEM231	TCTN1	psi-mi:“MI:0914”(association)	0.640
KNG1	CTSV	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
CDH23	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
CST9L	QSOX1	psi-mi:“MI:0914”(association)	0.350
NMS	MANBA	psi-mi:“MI:0914”(association)	0.350
TMEM25	NME4	psi-mi:“MI:0914”(association)	0.350
TMEM231	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
CD160	PLXNB2	psi-mi:“MI:0914”(association)	0.350
IDS	COCH	psi-mi:“MI:0914”(association)	0.350
DEFB109B	CHST10	psi-mi:“MI:0914”(association)	0.350
EDDM3A	PLXNA2	psi-mi:“MI:0914”(association)	0.350
LCN9	C1QL1	psi-mi:“MI:0914”(association)	0.350
B9D2	PARN	psi-mi:“MI:0914”(association)	0.350
TCTN1	NPTX1	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
CST11	PLXNB2	psi-mi:“MI:0914”(association)	0.350
TCTN1	GUSB	psi-mi:“MI:0914”(association)	0.350
TCTN1	TOR1A	psi-mi:“MI:2364”(proximity)	0.270
TCTN1	PLOD2	psi-mi:“MI:2364”(proximity)	0.270
TCTN3	TCTN1	psi-mi:“MI:0915”(physical association)	0.000
TCTN2	TCTN1	psi-mi:“MI:0915”(physical association)	0.000
TMEM231	TCTN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (173): TCTN1 (Affinity Capture-MS), TCTN1 (Affinity Capture-MS), TCTN1 (Affinity Capture-MS), TCTN1 (Affinity Capture-MS), TCTN1 (Affinity Capture-MS), ASPH (Proximity Label-MS), BCAP31 (Proximity Label-MS), BRI3BP (Proximity Label-MS), CALR (Proximity Label-MS), CALU (Proximity Label-MS), CANX (Proximity Label-MS), CCDC134 (Proximity Label-MS), CKAP4 (Proximity Label-MS), CNPY2 (Proximity Label-MS), CNPY3 (Proximity Label-MS)

ESM2 similar proteins: A2A6C4, A4D0V7, A4FV27, A6QQ85, A7VL23, A8MWV9, B0FP48, D4A6L0, E1BBQ2, E5RIL1, O54715, O73698, O75129, O75631, O76095, P0C8N6, P38574, P40682, Q14C87, Q14DG7, Q15904, Q2MV58, Q3UN70, Q3ZBK7, Q52LC2, Q5PPI4, Q5T848, Q5ZJY9, Q60943, Q61137, Q6PGD0, Q76HP2, Q76HP3, Q80YF6, Q80Z10, Q864V4, Q8BZ64, Q8C419, Q8CB65, Q8CEF9

Diamond homologs: Q2MV58, Q4R9E0, Q6NUS6, Q8BZ64, Q8R2Q6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	29
Uncertain significance	183
Likely benign	196
Benign	23

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1033279	NM_001082538.3(TCTN1):c.26_29dup (p.Val11fs)	Pathogenic
1252090	NM_001082538.3(TCTN1):c.1385dup (p.Trp463fs)	Pathogenic
1374749	NM_001082538.3(TCTN1):c.156del (p.Arg52fs)	Pathogenic
1374980	NM_001082538.3(TCTN1):c.1465del (p.His489fs)	Pathogenic
1406500	NM_001082538.3(TCTN1):c.1527del (p.Ala511fs)	Pathogenic
1410963	NM_001082538.3(TCTN1):c.736A>T (p.Lys246Ter)	Pathogenic
1454973	NM_001082538.3(TCTN1):c.1775_1778del (p.Val592fs)	Pathogenic
1455274	NC_000012.11:g.(?111064147)(111064317_?)del	Pathogenic
1805072	NM_001082538.3(TCTN1):c.378_381dup (p.Ser128fs)	Pathogenic
183312	NM_001082538.3(TCTN1):c.342-2A>G	Pathogenic
1903848	NM_001082538.3(TCTN1):c.822+1G>A	Pathogenic
2000289	NM_001082538.3(TCTN1):c.210dup (p.Val71fs)	Pathogenic
212386	NM_001082538.3(TCTN1):c.843+1del	Pathogenic
221983	NM_001082538.3(TCTN1):c.898C>T (p.Arg300Ter)	Pathogenic
2423665	NC_000012.11:g.(?111064147)(111074326_?)del	Pathogenic
2921929	NM_001082538.3(TCTN1):c.256_257del (p.Gln86fs)	Pathogenic
2939936	NM_001082538.3(TCTN1):c.209_210del (p.Pro70fs)	Pathogenic
2942895	NM_001082538.3(TCTN1):c.962del (p.Val321fs)	Pathogenic
2948555	NM_001082538.3(TCTN1):c.1505dup (p.Leu502fs)	Pathogenic
30803	NM_001082538.3(TCTN1):c.221-2A>G	Pathogenic
3244265	NC_000012.11:g.(?111057621)(111057781_?)del	Pathogenic
3366343	NM_001082538.3(TCTN1):c.291C>A (p.Cys97Ter)	Pathogenic
3366636	NM_001082538.3(TCTN1):c.1114dup (p.Gln372fs)	Pathogenic
3752289	NM_001082538.3(TCTN1):c.514G>T (p.Glu172Ter)	Pathogenic
4277234	NM_001082538.3(TCTN1):c.342-2A>C	Pathogenic
4784183	NM_001082538.3(TCTN1):c.1159_1160dup (p.Leu388fs)	Pathogenic
4793524	NM_001082538.3(TCTN1):c.256C>T (p.Gln86Ter)	Pathogenic
4848272	NM_001082538.3(TCTN1):c.1133del (p.Gly378fs)	Pathogenic
829835	NM_001082538.3(TCTN1):c.1454G>A (p.Trp485Ter)	Pathogenic
833489	NC_000012.12:g.(?110626342)(110642409_?)del	Pathogenic

SpliceAI

3540 predictions. Top by Δscore:

Variant	Effect	Δscore
12:110619834:A:AG	acceptor_gain	1.0000
12:110619835:G:GG	acceptor_gain	1.0000
12:110619952:GTCAC:G	donor_gain	1.0000
12:110619957:G:GG	donor_gain	1.0000
12:110626360:A:AG	acceptor_gain	1.0000
12:110626360:AG:A	acceptor_gain	1.0000
12:110626360:AGG:A	acceptor_gain	1.0000
12:110626361:G:GG	acceptor_gain	1.0000
12:110626361:GG:G	acceptor_gain	1.0000
12:110626361:GGG:G	acceptor_gain	1.0000
12:110626361:GGGGC:G	acceptor_gain	1.0000
12:110626488:AAACT:A	donor_gain	1.0000
12:110626489:AACT:A	donor_gain	1.0000
12:110626489:AACTG:A	donor_loss	1.0000
12:110626490:ACT:A	donor_gain	1.0000
12:110626490:ACTG:A	donor_loss	1.0000
12:110626491:CT:C	donor_gain	1.0000
12:110626491:CTG:C	donor_loss	1.0000
12:110626492:TGT:T	donor_loss	1.0000
12:110626493:G:GG	donor_gain	1.0000
12:110626493:GT:G	donor_loss	1.0000
12:110626494:T:G	donor_loss	1.0000
12:110626495:AAG:A	donor_loss	1.0000
12:110628796:GAA:G	acceptor_gain	1.0000
12:110628916:GAGGT:G	donor_loss	1.0000
12:110628917:AGGTG:A	donor_loss	1.0000
12:110632470:A:AG	acceptor_gain	1.0000
12:110632470:AGTAT:A	acceptor_gain	1.0000
12:110632471:G:GG	acceptor_gain	1.0000
12:110632471:GTAT:G	acceptor_gain	1.0000

AlphaMissense

3845 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:110632538:T:A	C231S	0.989
12:110632539:G:C	C231S	0.989
12:110642355:T:C	F433L	0.988
12:110642357:T:A	F433L	0.988
12:110642357:T:G	F433L	0.988
12:110634696:T:A	C247S	0.986
12:110634697:G:C	C247S	0.986
12:110642379:T:A	C441S	0.986
12:110642380:G:C	C441S	0.986
12:110647797:T:C	F557L	0.986
12:110647799:T:A	F557L	0.986
12:110647799:T:G	F557L	0.986
12:110634696:T:C	C247R	0.985
12:110634672:T:C	F239L	0.983
12:110634674:T:A	F239L	0.983
12:110634674:T:G	F239L	0.983
12:110642356:T:G	F433C	0.983
12:110647792:T:A	V555D	0.983
12:110632538:T:C	C231R	0.981
12:110619904:T:A	C97S	0.979
12:110619905:G:C	C97S	0.979
12:110626378:T:A	C120S	0.979
12:110626379:G:C	C120S	0.979
12:110619893:G:A	C93Y	0.978
12:110647253:T:A	W513R	0.978
12:110647253:T:C	W513R	0.978
12:110619847:T:A	C78S	0.976
12:110619848:G:C	C78S	0.976
12:110619874:T:A	C87S	0.976
12:110619875:G:C	C87S	0.976

dbSNP variants (sampled 300 via entrez): RS1000015790 (12:110637145 C>T), RS1000026923 (12:110621966 C>G,T), RS1000055727 (12:110615677 T>A), RS1000128821 (12:110617081 G>A), RS1000163701 (12:110621625 A>G), RS1000323487 (12:110615895 C>T), RS1000332607 (12:110635485 G>T), RS1000536602 (12:110627340 T>A,C), RS1000692619 (12:110633723 C>T), RS1000743230 (12:110649028 TTTTC>T,TTTTCTTTC), RS1000806883 (12:110633336 C>T), RS1000990780 (12:110626639 G>A,T), RS1001138081 (12:110615879 A>C,G), RS1001150475 (12:110637360 T>C), RS1001233529 (12:110641257 A>G)

Disease associations

OMIM: gene MIM:609863 | disease phenotypes: MIM:213300, MIM:249000, MIM:614173

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 13	Strong	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive
Meckel syndrome	Supportive	Autosomal recessive

Mondo (4): Joubert syndrome (MONDO:0018772), Meckel syndrome (MONDO:0018921), Joubert syndrome 13 (MONDO:0013608), Joubert syndrome and related disorders (MONDO:0015369)

Orphanet (3): Isolated Joubert syndrome (Orphanet:475), Meckel syndrome (Orphanet:564), Joubert syndrome and related disorders (Orphanet:140874)

HPO phenotypes

80 total (30 of 80 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:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
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:0000482	Microcornea
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000532	Abnormal chorioretinal morphology
HP:0000568	Microphthalmia
HP:0000612	Iris coloboma

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002783_383	Body mass index	7.000000e-06
GCST002783_540	Body mass index	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Arsenic	decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
nickel sulfate	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
deguelin	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Antimycin A	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Lead	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Phenobarbital	affects expression	1
Rotenone	decreases expression	1
Selenium	affects cotreatment, decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)