TCTN3

Summary

TCTN3 (tectonic family member 3, HGNC:24519) is a protein-coding gene on chromosome 10q24.1, encoding Tectonic-3 (Q6NUS6). Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition.

This gene encodes a member of the tectonic gene family which functions in Hedgehog signal transduction and development of the neural tube. Mutations in this gene have been associated with Orofaciodigital Syndrome IV and Joubert Syndrom 18. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 26123 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 549 total — 36 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 179
• MANE Select transcript: NM_015631

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24519
Approved symbol	TCTN3
Name	tectonic family member 3
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564D116, TECT3, JBTS18
Ensembl gene	ENSG00000119977
Ensembl biotype	protein_coding
OMIM	613847
Entrez	26123

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 26 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000265993, ENST00000371209, ENST00000371217, ENST00000430368, ENST00000478245, ENST00000497399, ENST00000614499, ENST00000679485, ENST00000679566, ENST00000679984, ENST00000680144, ENST00000680353, ENST00000680697, ENST00000680709, ENST00000680781, ENST00000681127, ENST00000681185, ENST00000681739, ENST00000681928, ENST00000898866, ENST00000898867, ENST00000898868, ENST00000898869, ENST00000898870, ENST00000898871, ENST00000898872, ENST00000898873, ENST00000939774, ENST00000939775, ENST00000939776, ENST00000939777, ENST00000956556, ENST00000956557, ENST00000956558, ENST00000956559

RefSeq mRNA: 3 — MANE Select: NM_015631 NM_001143973, NM_001410982, NM_015631

CCDS: CCDS31258, CCDS44461, CCDS91309

Canonical transcript exons

ENST00000371217 — 14 exons

Exon	Start	End
ENSE00001942029	95663401	95664300
ENSE00003241277	95687592	95687719
ENSE00003290538	95687044	95687159
ENSE00003353265	95686495	95686530
ENSE00003353364	95687247	95687355
ENSE00003358882	95684499	95684624
ENSE00003381433	95682651	95682804
ENSE00003390139	95680472	95680609
ENSE00003393384	95683101	95683195
ENSE00003418098	95683522	95683629
ENSE00003450960	95685556	95685636
ENSE00003559041	95693353	95693476
ENSE00003572752	95692920	95693038
ENSE00003708213	95693644	95693927

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 95.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.2660 / max 179.2908, expressed in 1814 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110825	27.5460	1804
110826	7.6885	1737
110824	3.8938	1324
110823	0.1376	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	95.02	gold quality
decidua	UBERON:0002450	92.94	gold quality
stromal cell of endometrium	CL:0002255	92.52	gold quality
islet of Langerhans	UBERON:0000006	92.45	gold quality
caput epididymis	UBERON:0004358	91.89	gold quality
right lobe of thyroid gland	UBERON:0001119	91.84	gold quality
pancreatic ductal cell	CL:0002079	91.53	silver quality
left lobe of thyroid gland	UBERON:0001120	91.42	gold quality
gall bladder	UBERON:0002110	91.29	gold quality
thyroid gland	UBERON:0002046	91.16	gold quality
cauda epididymis	UBERON:0004360	90.84	gold quality
rectum	UBERON:0001052	90.77	gold quality
parotid gland	UBERON:0001831	90.56	gold quality
right ovary	UBERON:0002118	90.41	gold quality
left ovary	UBERON:0002119	90.30	gold quality
bronchial epithelial cell	CL:0002328	90.25	gold quality
ventricular zone	UBERON:0003053	90.19	gold quality
right adrenal gland	UBERON:0001233	90.02	gold quality
left adrenal gland	UBERON:0001234	89.89	gold quality
right uterine tube	UBERON:0001302	89.83	gold quality
right adrenal gland cortex	UBERON:0035827	89.80	gold quality
right coronary artery	UBERON:0001625	89.79	gold quality
pancreas	UBERON:0001264	89.61	gold quality
left coronary artery	UBERON:0001626	89.56	gold quality
left adrenal gland cortex	UBERON:0035825	89.51	gold quality
body of uterus	UBERON:0009853	89.46	gold quality
body of pancreas	UBERON:0001150	89.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.28	gold quality
ovary	UBERON:0000992	89.21	gold quality
pigmented layer of retina	UBERON:0001782	89.19	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)

43 targeting TCTN3, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-325	99.58	66.55	358
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-10226	98.25	66.50	811

Literature-anchored findings (GeneRIF, showing 3)

• TCTN3 mutations cause Mohr-Majewski syndrome. (PMID:22883145)
• Novel mutations of TCTN3/LTBP2 with cellular function changes in congenital heart disease associated with polydactyly. (PMID:33098376)
• A splice site variant in TCTN3 underlies an atypical form of orofaciodigital syndrome IV. (PMID:36039988)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tctn3	ENSMUSG00000025008
rattus_norvegicus	Tctn3	ENSRNOG00000062728
caenorhabditis_elegans		WBGENE00017120

Paralogs (2): TCTN2 (ENSG00000168778), TCTN1 (ENSG00000204852)

Protein

Protein identifiers

Tectonic-3 — Q6NUS6 (reviewed: Q6NUS6)

All UniProt accessions (9): A0A0C4DFN5, A0A7P0T8X6, A0A7P0T987, Q6NUS6, A0A7P0T9R6, A0A7P0TA00, A0A7P0TA64, A0A7P0TB57, A0A804G9W2

UniProt curated annotations — full annotation on UniProt →

Function. Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. May be involved in apoptosis regulation. Necessary for signal transduction through the sonic hedgehog (Shh) signaling pathway.

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

Subcellular location. Membrane.

Disease relevance. Orofaciodigital syndrome 4 (OFD4) [MIM:258860] A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD4 patients have tongue nodules, multiple frenulae, broad flat nose, hypertelorism, and short rib polydactyly with tibial dysplasia (Majewski syndrome). The presence of severe tibial aplasia differentiates OFD4 from OFD1. Additional features of cystic dysplastic kidneys and brain malformation, including occipital encephalocele, are observed in severely affected patients. The disease is caused by variants affecting the gene represented in this entry. Joubert syndrome 18 (JBTS18) [MIM:614815] 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 and renal disease. JBTS18 patients have vermis agenesis and the molar tooth sign as well as severe kyphoscoliosis. Other features include intrauterine growth retardation, oral anomalies, micrognathism, polydactyly and camptodactyly, joint laxity, horseshoe kidney, and ventricular septal defect. The disease is caused by variants affecting the gene represented in this entry. TCTN3-mutated fibroblasts from JBTS18 patients fail to respond to Shh agonists suggesting that at least some of the defects in affected individuals may be secondary to reduced Shh signaling.

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 (5)

UniProt ID	Names	Canonical?
Q6NUS6-1	1	yes
Q6NUS6-2	2
Q6NUS6-3	3
Q6NUS6-4	4
Q6NUS6-5	5

RefSeq proteins (3): NP_001137445, NP_001397911, NP_056446* (*=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 (23 total): splice variant 8, sequence conflict 3, glycosylation site 3, sequence variant 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUS6-F1	71.49	0.27

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): 78, 179, 347

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: 495 (showing top): RRAGTTGT_UNKNOWN, WANG_CLIM2_TARGETS_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, EFC_Q6, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_CELL_PROJECTION_ORGANIZATION, TGGAAA_NFAT_Q4_01

GO Biological Process (5): apoptotic process (GO:0006915), smoothened signaling pathway (GO:0007224), positive regulation of apoptotic process (GO:0043065), cilium assembly (GO:0060271), cell projection organization (GO:0030030)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), ciliary membrane (GO:0060170), membrane (GO:0016020)

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
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell surface receptor signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	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
binding	1
intracellular membrane-bounded organelle	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCTN3	B9D1	Q9UPM9	969
TCTN3	CC2D2A	Q9P2K1	968
TCTN3	TCTN1	Q2MV58	960
TCTN3	TMEM216	Q9P0N5	943
TCTN3	TCTN2	Q96GX1	938
TCTN3	TMEM67	Q5HYA8	925
TCTN3	CEP290	O15078	910
TCTN3	B9D2	Q9BPU9	895
TCTN3	MKS1	Q9NXB0	890
TCTN3	TMEM231	Q9H6L2	879
TCTN3	TMEM237	Q96Q45	829
TCTN3	AHI1	Q8N157	807
TCTN3	NPHP1	O15259	783
TCTN3	TMEM17	Q86X19	778
TCTN3	CPLANE1	Q9H799	772

IntAct

29 interactions, top by confidence:

A	B	Type	Score
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
TCTN2	TCTN3	psi-mi:“MI:0914”(association)	0.640
BAG6	TCTN3	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TCTN3	GPAA1	psi-mi:“MI:0914”(association)	0.480
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
TCTN3	CFTR	psi-mi:“MI:0915”(physical association)	0.370
rep	BMPR1B	psi-mi:“MI:0914”(association)	0.350
	TOR1B	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
APOM	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ISLR		psi-mi:“MI:0914”(association)	0.350
TCTN1	GUSB	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
FBXO6	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LCN6	HIGD1C	psi-mi:“MI:0914”(association)	0.350
TCTN3	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270
B9D2	RGPD3	psi-mi:“MI:2364”(proximity)	0.270
TCTN3	TCTN1	psi-mi:“MI:0915”(physical association)	0.000
TCTN2	TCTN3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (352): TCTN3 (Affinity Capture-RNA), TCTN3 (Affinity Capture-RNA), TGM1 (Affinity Capture-MS), CTSH (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), CSTA (Affinity Capture-MS), CPA4 (Affinity Capture-MS), KPRP (Affinity Capture-MS), TCTN3 (Proximity Label-MS), AAAS (Proximity Label-MS), ABCB10 (Proximity Label-MS), ABHD12 (Proximity Label-MS), ACADSB (Proximity Label-MS), ACSL3 (Proximity Label-MS), ADIPOR2 (Proximity Label-MS)

ESM2 similar proteins: O00115, O08590, O15547, O46406, O62855, O70423, O95897, P10820, P14222, P34387, P35763, P36633, P56541, P56542, Q04912, Q16853, Q17778, Q24K15, Q29437, Q2KJC3, Q2T8B0, Q3JJK4, Q3V5L5, Q4R9E0, Q5R9I0, Q5SSH8, Q62190, Q63IT3, Q6AX53, Q6NUS6, Q6TMA8, Q71SY6, Q75WF2, Q765H6, Q812C9, Q8JZQ5, Q8R2Q6, Q8WZ79, Q91ZV7, Q93086

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
Anchoring of the basal body to the plasma membrane	5	25.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	5	31.2×	6e-05
cilium assembly	5	12.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	36
Likely pathogenic	20
Uncertain significance	228
Likely benign	199
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1393536	NM_015631.6(TCTN3):c.338_341del (p.His113fs)	Pathogenic
1420657	NM_015631.6(TCTN3):c.940G>T (p.Gly314Ter)	Pathogenic
1429071	NM_015631.6(TCTN3):c.754del (p.Ser252fs)	Pathogenic
1451445	NM_015631.6(TCTN3):c.717_718del (p.Cys239_Ala240insTer)	Pathogenic
1451811	NM_015631.6(TCTN3):c.908_911del (p.Leu303fs)	Pathogenic
1459264	NM_015631.6(TCTN3):c.650_653del (p.Tyr217fs)	Pathogenic
2010930	NM_015631.6(TCTN3):c.1226del (p.Gly409fs)	Pathogenic
2027808	NM_015631.6(TCTN3):c.910dup (p.Thr304fs)	Pathogenic
2034806	NM_015631.6(TCTN3):c.2T>C (p.Met1Thr)	Pathogenic
2086552	NM_015631.6(TCTN3):c.920_941del (p.Ala307fs)	Pathogenic
2108190	NM_015631.6(TCTN3):c.793dup (p.Ser265fs)	Pathogenic
2120440	NM_015631.6(TCTN3):c.1206dup (p.Thr403fs)	Pathogenic
2129810	NM_015631.6(TCTN3):c.412_413del (p.Val138fs)	Pathogenic
2193739	NM_015631.6(TCTN3):c.1164dup (p.Lys389fs)	Pathogenic
2199048	NM_015631.6(TCTN3):c.1068dup (p.Gln357fs)	Pathogenic
2413854	NM_015631.6(TCTN3):c.737_738insC (p.Leu248fs)	Pathogenic
2927732	NM_015631.6(TCTN3):c.28C>T (p.Gln10Ter)	Pathogenic
2946329	NM_015631.6(TCTN3):c.1367_1370dup (p.Glu457fs)	Pathogenic
2950265	NM_015631.6(TCTN3):c.371_372del (p.Gly124fs)	Pathogenic
2953560	NM_015631.6(TCTN3):c.851dup (p.Val285fs)	Pathogenic
3063950	NM_015631.6(TCTN3):c.615del (p.Ser206fs)	Pathogenic
3244905	NC_000010.10:g.(?97452751)(97453767_?)del	Pathogenic
3340482	NM_015631.6(TCTN3):c.853-1G>T	Pathogenic
37056	NM_015631.6(TCTN3):c.1222C>T (p.Gln408Ter)	Pathogenic
37059	NM_015631.6(TCTN3):c.566_567del (p.Glu189fs)	Pathogenic
37060	NM_015631.6(TCTN3):c.1348_1349del (p.Leu450fs)	Pathogenic
37061	NM_015631.6(TCTN3):c.940G>A (p.Gly314Arg)	Pathogenic
3750737	NC_000010.11:g.95682805del	Pathogenic
3753414	NM_015631.6(TCTN3):c.63dup (p.Pro22fs)	Pathogenic
4785927	NM_015631.6(TCTN3):c.1020del (p.Val341fs)	Pathogenic

SpliceAI

2003 predictions. Top by Δscore:

Variant	Effect	Δscore
10:95682649:A:AC	donor_gain	1.0000
10:95682650:C:CC	donor_gain	1.0000
10:95683560:T:TA	donor_gain	1.0000
10:95684496:AAC:A	donor_gain	1.0000
10:95684497:AC:A	donor_gain	1.0000
10:95684498:CC:C	donor_gain	1.0000
10:95692918:A:AC	donor_gain	1.0000
10:95692919:C:CC	donor_gain	1.0000
10:95693477:C:CC	acceptor_gain	1.0000
10:95693638:CCTCA:C	donor_loss	1.0000
10:95693639:CTCA:C	donor_loss	1.0000
10:95693640:TCACC:T	donor_loss	1.0000
10:95693641:CACC:C	donor_loss	1.0000
10:95664299:TCC:T	acceptor_loss	0.9900
10:95664300:CCTA:C	acceptor_loss	0.9900
10:95664301:C:CC	acceptor_gain	0.9900
10:95664301:CTA:C	acceptor_loss	0.9900
10:95664302:T:C	acceptor_loss	0.9900
10:95682644:T:A	donor_gain	0.9900
10:95682650:CTGAA:C	donor_gain	0.9900
10:95682665:G:A	donor_gain	0.9900
10:95682732:CT:C	donor_gain	0.9900
10:95683226:C:CT	acceptor_gain	0.9900
10:95683528:A:C	donor_gain	0.9900
10:95683532:A:AC	donor_gain	0.9900
10:95683532:ATAT:A	donor_gain	0.9900
10:95683561:C:A	donor_gain	0.9900
10:95683628:GCC:G	acceptor_loss	0.9900
10:95683629:CCT:C	acceptor_loss	0.9900
10:95683630:C:CA	acceptor_loss	0.9900

AlphaMissense

3949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:95687155:G:C	F247L	0.990
10:95687155:G:T	F247L	0.990
10:95687157:A:G	F247L	0.990
10:95692937:C:G	C161S	0.989
10:95692938:A:T	C161S	0.989
10:95683133:A:C	F422L	0.988
10:95683133:A:T	F422L	0.988
10:95683135:A:G	F422L	0.988
10:95687267:C:G	C239S	0.988
10:95687268:A:T	C239S	0.988
10:95687132:C:G	C255S	0.987
10:95687133:A:T	C255S	0.987
10:95693021:C:G	C133S	0.987
10:95693022:A:T	C133S	0.987
10:95683134:A:C	F422C	0.985
10:95687131:G:C	C255W	0.984
10:95687133:A:G	C255R	0.984
10:95687156:A:C	F247C	0.984
10:95687156:A:G	F247S	0.983
10:95693437:C:G	C99S	0.983
10:95693438:A:T	C99S	0.983
10:95685575:C:G	C317S	0.982
10:95685576:A:T	C317S	0.982
10:95693424:G:C	C103W	0.982
10:95693458:C:G	C92S	0.982
10:95693459:A:T	C92S	0.982
10:95664253:A:C	F546L	0.981
10:95664253:A:T	F546L	0.981
10:95664255:A:G	F546L	0.981
10:95687099:C:G	C266S	0.981

dbSNP variants (sampled 300 via entrez): RS1000000537 (10:95670390 C>T), RS1000021096 (10:95679185 T>C), RS1000037091 (10:95685175 T>G), RS1000073548 (10:95667921 C>T), RS1000106430 (10:95670615 G>A), RS1000185704 (10:95677745 C>T), RS1000317850 (10:95678097 A>C), RS1000338302 (10:95676953 A>T), RS1000348298 (10:95692369 G>A), RS1000444076 (10:95684309 A>T), RS1000455106 (10:95664370 A>G), RS1000457077 (10:95684772 T>A,C), RS1000480505 (10:95671352 G>A), RS1000793629 (10:95682958 G>C), RS1000891403 (10:95663463 G>A)

Disease associations

OMIM: gene MIM:613847 | disease phenotypes: MIM:258860, MIM:614815

GenCC curated gene-disease

Disease	Classification	Inheritance
orofaciodigital syndrome IV	Definitive	Autosomal recessive
Joubert syndrome 18	Strong	Autosomal recessive
orofaciodigital syndrome type 6	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
ciliopathy	Definitive	AR

Mondo (6): orofaciodigital syndrome IV (MONDO:0009794), Joubert syndrome 18 (MONDO:0013896), Joubert syndrome and related disorders (MONDO:0015369), ciliopathy (MONDO:0005308), orofaciodigital syndrome type 6 (MONDO:0010176), Meckel syndrome (MONDO:0018921)

Orphanet (4): Orofaciodigital syndrome type 4 (Orphanet:2753), Orofaciodigital syndrome type 6 (Orphanet:2754), Joubert syndrome and related disorders (Orphanet:140874), Ciliopathy (Orphanet:363250)

HPO phenotypes

179 total (30 of 179 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:0000085	Horseshoe kidney
HP:0000104	Renal agenesis
HP:0000107	Renal cyst
HP:0000143	Rectovaginal fistula
HP:0000157	Abnormality of the tongue
HP:0000161	Median cleft upper lip
HP:0000168	Abnormality of the gingiva
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000191	Accessory oral frenulum
HP:0000193	Bifid uvula
HP:0000199	Tongue nodules
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000293	Full cheeks

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537133	Orofaciodigital syndrome 4 (supp.)
C536531	Orofaciodigital syndrome 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants, Occupational	affects expression	1
Arsenic	affects expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT00068224	Not specified	COMPLETED	Clinical and Molecular Investigations Into Ciliopathies
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)