CPLANE1

Summary

CPLANE1 (ciliogenesis and planar polarity effector complex subunit 1, HGNC:25801) is a protein-coding gene on chromosome 5p13.2, encoding Ciliogenesis and planar polarity effector 1 (Q9H799). Involved in ciliogenesis.

The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS).

Source: NCBI Gene 65250 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 17 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 2,682 total — 190 pathogenic, 123 likely-pathogenic
• Phenotypes (HPO): 110
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001384732

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25801
Approved symbol	CPLANE1
Name	ciliogenesis and planar polarity effector complex subunit 1
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13231, JBTS17, Hug
Ensembl gene	ENSG00000197603
Ensembl biotype	protein_coding
OMIM	614571
Entrez	65250

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 11 retained_intron, 5 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000425232, ENST00000504716, ENST00000505121, ENST00000505431, ENST00000508244, ENST00000508405, ENST00000509849, ENST00000509957, ENST00000510830, ENST00000511210, ENST00000511781, ENST00000512288, ENST00000514429, ENST00000515380, ENST00000651892, ENST00000675149, ENST00000675547, ENST00000676160, ENST00000676290, ENST00000676304, ENST00000913843, ENST00000955438

RefSeq mRNA: 2 — MANE Select: NM_001384732 NM_001384732, NM_023073

CCDS: CCDS34146, CCDS93707

Canonical transcript exons

ENST00000651892 — 53 exons

Exon	Start	End
ENSE00001608181	37180857	37181005
ENSE00001608716	37186286	37186394
ENSE00001633863	37195858	37195996
ENSE00001708977	37187733	37187842
ENSE00001725577	37177621	37177700
ENSE00001726665	37179361	37179443
ENSE00001738823	37198702	37198866
ENSE00001764752	37168791	37169561
ENSE00001764998	37182760	37183699
ENSE00001783637	37175909	37175986
ENSE00001790014	37187414	37187572
ENSE00001802130	37184788	37185079
ENSE00002026534	37180017	37180183
ENSE00003244578	37165539	37165671
ENSE00003292210	37162465	37162566
ENSE00003295970	37167047	37167213
ENSE00003354710	37164273	37164327
ENSE00003471726	37114960	37115049
ENSE00003473729	37224532	37224740
ENSE00003475868	37142310	37142480
ENSE00003475902	37139340	37139370
ENSE00003489798	37122430	37122488
ENSE00003491421	37205315	37205454
ENSE00003492124	37206197	37206425
ENSE00003499405	37239713	37239869
ENSE00003514328	37173755	37173947
ENSE00003524484	37170041	37170331
ENSE00003539299	37125244	37125409
ENSE00003552675	37245710	37245845
ENSE00003554365	37213559	37213732
ENSE00003561288	37108293	37108471
ENSE00003585728	37244375	37244607
ENSE00003588677	37138720	37138848
ENSE00003595466	37247618	37247745
ENSE00003608965	37201591	37201808
ENSE00003619366	37245479	37245598
ENSE00003626076	37227243	37227392
ENSE00003631438	37148181	37148268
ENSE00003634230	37226304	37227073
ENSE00003638125	37227568	37227817
ENSE00003641427	37238857	37238960
ENSE00003650288	37121617	37121784
ENSE00003656390	37158224	37158345
ENSE00003665918	37120216	37120340
ENSE00003672708	37224253	37224333
ENSE00003676039	37243013	37243119
ENSE00003676906	37157313	37157420
ENSE00003680446	37157670	37157868
ENSE00003688647	37230867	37231049
ENSE00003690086	37221324	37221488
ENSE00003787048	37153740	37153993
ENSE00003848441	37249245	37249376
ENSE00003903413	37106235	37107778

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 92.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2331 / max 117.3153, expressed in 1686 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61331	11.2186	1686
203524	0.0145	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.27	gold quality
calcaneal tendon	UBERON:0003701	90.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.89	gold quality
cortical plate	UBERON:0005343	89.35	gold quality
ventricular zone	UBERON:0003053	89.31	gold quality
adrenal tissue	UBERON:0018303	88.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.12	gold quality
cerebellar hemisphere	UBERON:0002245	86.01	gold quality
cerebellar cortex	UBERON:0002129	85.90	gold quality
ganglionic eminence	UBERON:0004023	85.84	gold quality
right uterine tube	UBERON:0001302	85.67	gold quality
germinal epithelium of ovary	UBERON:0001304	85.11	gold quality
colonic epithelium	UBERON:0000397	84.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.49	gold quality
stromal cell of endometrium	CL:0002255	84.34	gold quality
right frontal lobe	UBERON:0002810	83.82	gold quality
tibial nerve	UBERON:0001323	83.72	gold quality
left lobe of thyroid gland	UBERON:0001120	83.49	gold quality
mucosa of stomach	UBERON:0001199	83.19	gold quality
adenohypophysis	UBERON:0002196	82.78	gold quality
cerebellum	UBERON:0002037	82.70	gold quality
thyroid gland	UBERON:0002046	82.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.27	gold quality
right lobe of thyroid gland	UBERON:0001119	82.04	gold quality
left ovary	UBERON:0002119	81.71	gold quality
anterior cingulate cortex	UBERON:0009835	81.54	gold quality
cingulate cortex	UBERON:0003027	81.43	gold quality
tendon	UBERON:0000043	81.19	gold quality
body of uterus	UBERON:0009853	81.17	gold quality
right ovary	UBERON:0002118	81.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.15
E-MTAB-7381	no	245.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting CPLANE1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-296-3P	99.21	66.56	474

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 14)

• C5orf42 and KIAA1377 gene synergistically play a role as susceptibility genes for monomelic amyotrophy. (PMID:22264561)
• The data suggested that mutations in C5ORF42 explain a large percentage of French Canadian individuals with Joubert syndrome. (PMID:22425360)
• Exome sequencing revealed a likely pathogenic mutation in three novel candidate MKS disease genes-C5orf42, EVC2 and SEC8 (also known as EXOC4), which encodes an exocyst protein with an established role in ciliogenesis (PMID:23169490)
• We identified causal C5orf42 mutations in 9/11 families meeting OFD VI diagnostic criteria, but no mutation in individuals with partly overlapping features. (PMID:24178751)
• C5orf42 mutation is associated with Oral-facial-digital syndrome type VI. (PMID:25407461)
• C5orf42 is one of the causative genes for OFDVI. (PMID:25846457)
• In C5orf42-mutant Joubert syndrome patients, the infratentorial magnetic resonance images showed normal or minimally thickened and minimally elongated superior cerebellar peduncles, normal or minimally deepened interpeduncular fossa, and mild vermian hypoplasia. (PMID:28431631)
• Seven novel germline recessive mutations in CPLANE1, including missense, nonsense, frameshift and canonical splice site variants, were identified in OFD6 patients. (PMID:29605658)
• JBTS17 contributes to mitotic progression by interacting with LIS1, and abnormal mitosis is an underlying mechanism in JBTS17-related ciliopathies. (PMID:31004438)
• Four novel compound heterozygous mutations in C5orf42 gene in patients with pure and mild Joubert syndrome. (PMID:32233090)
• The proband with Jouber syndrome of family 2 was found to harbor compound heterozygous variants of the CPLANE1 gene, namely c.7243dupA (p.T2415Nfs*7) and c.8001delG (p.K2667Nfs*31), which can respectively lead to premature termination of translation of ciliogenesis and planar polarity effector 1 after the 2145th and 2667th amino acids (PMID:32335874)
• Salivary CPLANE1 Levels as a Biomarker of Oral Squamous Cell Carcinoma. (PMID:33517281)
• Clinical heterogeneity and intrafamilial variability of Joubert syndrome in two siblings with CPLANE1 variants. (PMID:33822487)
• Exome sequencing and RNA analysis identify two novel CPLANE1 variants causing Joubert syndrome. (PMID:35092359)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cplane1	ENSMUSG00000039801
rattus_norvegicus	Cplane1	ENSRNOG00000042118

Protein

Protein identifiers

Ciliogenesis and planar polarity effector 1 — Q9H799 (reviewed: Q9H799)

Alternative names: Protein JBTS17

All UniProt accessions (5): A0A494BZW6, A0A7I2XYG4, Q9H799, H0Y9I8, H0YA77

UniProt curated annotations — full annotation on UniProt →

Function. Involved in ciliogenesis. Involved in the establishment of cell polarity required for directional cell migration. Proposed to act in association with the CPLANE (ciliogenesis and planar polarity effectors) complex. Involved in recruitment of peripheral IFT-A proteins to basal bodies.

Subunit / interactions. Interacts with FUZ; INTU and WDPCP; the interactors are proposed to form the core CPLANE (ciliogenesis and planar polarity effectors) complex.

Subcellular location. Membrane. Cell projection. Cilium.

Disease relevance. Joubert syndrome 17 (JBTS17) [MIM:614615] 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. Orofaciodigital syndrome 6 (OFD6) [MIM:277170] 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. OFD6 is characterized by metacarpal abnormalities with central polydactyly, cerebellar abnormalities including the molar tooth sign, tongue hamartomas, additional frenula, and upper lip notch. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H799-1	1	yes
Q9H799-5	2

RefSeq proteins (2): NP_001371661, NP_075561 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028236	CPLANE1	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF15392

UniProt features (59 total): sequence variant 27, sequence conflict 8, compositionally biased region 7, region of interest 7, splice variant 4, transmembrane region 2, coiled-coil region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9H799 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Post-translational modifications (1): 2407

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 309 (showing top): GCM_GSPT1, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, HAND1E47_01, GOBP_CELL_PROJECTION_ORGANIZATION, GATA4_Q3, GOCC_CILIARY_TRANSITION_ZONE, GOCC_CILIUM, HAMAI_APOPTOSIS_VIA_TRAIL_UP, WHITFIELD_CELL_CYCLE_S, JOHNSTONE_PARVB_TARGETS_3_DN, BCAT_GDS748_DN, BCAT.100_UP.V1_DN, GCM_RAB10, KRAS.PROSTATE_UP.V1_UP

GO Biological Process (12): cilium assembly (GO:0060271), establishment of planar polarity (GO:0001736), kidney development (GO:0001822), cardiac septum development (GO:0003279), ventricular septum development (GO:0003281), heart development (GO:0007507), cerebellum development (GO:0021549), cell projection organization (GO:0030030), embryonic digit morphogenesis (GO:0042733), roof of mouth development (GO:0060021), coronary vasculature development (GO:0060976), protein localization to ciliary transition zone (GO:1904491)

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

GO Cellular Component (4): membrane (GO:0016020), ciliary transition zone (GO:0035869), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
cellular anatomical structure	3
protein localization to cilium	2
animal organ development	2
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
morphogenesis of a polarized epithelium	1
establishment of tissue polarity	1
renal system development	1
cardiac chamber development	1
cardiac ventricle development	1
cardiac septum development	1
circulatory system development	1
metencephalon development	1
cellular component organization	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
blood vessel development	1
heart development	1
binding	1
cilium	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPLANE1	WDR70	Q9NW82	934
CPLANE1	NUP155	O75694	915
CPLANE1	NIPBL	Q6KC79	787
CPLANE1	TMEM216	Q9P0N5	772
CPLANE1	TCTN3	Q6NUS6	772
CPLANE1	TMEM237	Q96Q45	726
CPLANE1	TMEM231	Q9H6L2	720
CPLANE1	TMEM138	Q9NPI0	720
CPLANE1	TMEM67	Q5HYA8	720
CPLANE1	CC2D2A	Q9P2K1	720
CPLANE1	OFD1	O75665	697
CPLANE1	AHI1	Q8N157	691
CPLANE1	TCTN1	Q2MV58	672
CPLANE1	TCTN2	Q96GX1	669
CPLANE1	NPHP1	O15259	666

IntAct

15 interactions, top by confidence:

A	B	Type	Score
AUH	CPLANE1	psi-mi:“MI:0915”(physical association)	0.400
CPLANE1	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400
CPLANE1	XRN2	psi-mi:“MI:0915”(physical association)	0.400
BRAP	CPLANE1	psi-mi:“MI:0915”(physical association)	0.370
CPLANE1	FXR1	psi-mi:“MI:0915”(physical association)	0.370
Cep135		psi-mi:“MI:0914”(association)	0.350
Anapc2	ANAPC15	psi-mi:“MI:0914”(association)	0.350
TUBGCP4	PZP	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
TESK2	ILVBL	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DISC1	CPLANE1	psi-mi:“MI:0915”(physical association)	0.000
ezrA	CPLANE1	psi-mi:“MI:0915”(physical association)	0.000
CPLANE1	PAK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): C5orf42 (Biochemical Activity), C5orf42 (Affinity Capture-MS), C5orf42 (Affinity Capture-MS), C5orf42 (Affinity Capture-MS), C5orf42 (Affinity Capture-RNA), C5orf42 (Proximity Label-MS), C5orf42 (Proximity Label-MS), C5orf42 (Proximity Label-MS), C5orf42 (Proximity Label-MS), C5orf42 (Two-hybrid), C5orf42 (Affinity Capture-MS), C5orf42 (Affinity Capture-MS), C5orf42 (Affinity Capture-MS), C5orf42 (Positive Genetic), C5orf42 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4I9Y1, A0A0R4IBK5, A2AN08, A2ARZ3, A5WUT8, A6NKT7, B1WBT0, B8RJM0, C9JQI7, E9Q3L2, E9Q555, H2QII6, O08662, O14715, O15050, O43310, O75592, O75969, P0DJD0, P0DJD1, P13864, P42356, P49792, Q0V9S3, Q0VF22, Q24K09, Q2TL32, Q4R6W9, Q4V847, Q63HN8, Q6PB60, Q6PEE2, Q71HP2, Q7TPH6, Q7TPV2, Q7Z3J3, Q80930, Q80TA9, Q810N5, Q811D2

Diamond homologs: Q8CE72, Q9H799

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“CPLANE complex”	“up-regulates activity”	CPLANE1	binding
CPLANE1	up-regulates	Cilium_assembly

Disease & clinical

Clinical variants and AI predictions

ClinVar

2682 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	190
Likely pathogenic	123
Uncertain significance	1207
Likely benign	802
Benign	116

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072803	NM_001384732.1(CPLANE1):c.3928G>T (p.Glu1310Ter)	Pathogenic
1076603	NM_001384732.1(CPLANE1):c.88G>T (p.Glu30Ter)	Pathogenic
1077152	NM_001384732.1(CPLANE1):c.9063C>A (p.Tyr3021Ter)	Pathogenic
1332773	NM_001384732.1(CPLANE1):c.7020dup (p.Leu2341fs)	Pathogenic
1352910	NM_001384732.1(CPLANE1):c.1041_1044dup (p.Thr349fs)	Pathogenic
1402222	NM_001384732.1(CPLANE1):c.3204dup (p.Gln1069fs)	Pathogenic
1413739	NM_001384732.1(CPLANE1):c.5629del (p.Ser1877fs)	Pathogenic
1415532	NM_001384732.1(CPLANE1):c.3906_3912del (p.Asn1302fs)	Pathogenic
1422168	NM_001384732.1(CPLANE1):c.1419_1420insTC (p.Leu475fs)	Pathogenic
1438014	NM_001384732.1(CPLANE1):c.5266del (p.Arg1756fs)	Pathogenic
1440465	NM_001384732.1(CPLANE1):c.2616T>A (p.Tyr872Ter)	Pathogenic
1445057	NM_001384732.1(CPLANE1):c.1199_1200del (p.Arg400fs)	Pathogenic
1451420	NM_001384732.1(CPLANE1):c.7402C>T (p.Gln2468Ter)	Pathogenic
1451870	NM_001384732.1(CPLANE1):c.8992C>T (p.Gln2998Ter)	Pathogenic
1452683	NM_001384732.1(CPLANE1):c.7399del (p.Arg2467fs)	Pathogenic
1453073	NM_001384732.1(CPLANE1):c.5833G>T (p.Glu1945Ter)	Pathogenic
1453338	NM_001384732.1(CPLANE1):c.7466del (p.Asn2489fs)	Pathogenic
1453802	NM_001384732.1(CPLANE1):c.7320del (p.Gly2441fs)	Pathogenic
1454259	NM_001384732.1(CPLANE1):c.2426T>A (p.Leu809Ter)	Pathogenic
1454445	NM_001384732.1(CPLANE1):c.9560del (p.Ser3187fs)	Pathogenic
1454521	NM_001384732.1(CPLANE1):c.3604C>T (p.Gln1202Ter)	Pathogenic
1455619	NM_001384732.1(CPLANE1):c.5594dup (p.Asn1865fs)	Pathogenic
1455966	NM_001384732.1(CPLANE1):c.2743dup (p.Ser915fs)	Pathogenic
1456335	NM_001384732.1(CPLANE1):c.6556del (p.Ser2186fs)	Pathogenic
1457872	NM_001384732.1(CPLANE1):c.8491dup (p.Asp2831fs)	Pathogenic
1458989	NM_001384732.1(CPLANE1):c.8568_8569del (p.Phe2857fs)	Pathogenic
1459257	NC_000005.9:g.(?37148263)(37148390_?)del	Pathogenic
1459695	NC_000005.9:g.(?36970958)(37371079_?)del	Pathogenic
1527154	GRCh37/hg19 5p13.2(chr5:36848530-37354525)	Pathogenic
157512	NM_001384732.1(CPLANE1):c.3150-1G>T	Pathogenic

SpliceAI

8996 predictions. Top by Δscore:

Variant	Effect	Δscore
5:37120337:CTCT:C	acceptor_gain	1.0000
5:37120339:CT:C	acceptor_gain	1.0000
5:37120341:C:CC	acceptor_gain	1.0000
5:37121615:AC:A	donor_gain	1.0000
5:37121616:CC:C	donor_gain	1.0000
5:37121616:CCCT:C	donor_gain	1.0000
5:37121785:C:CC	acceptor_gain	1.0000
5:37122425:CTCA:C	donor_loss	1.0000
5:37122426:TCACC:T	donor_loss	1.0000
5:37122427:CA:C	donor_loss	1.0000
5:37122429:CCTGT:C	donor_gain	1.0000
5:37122489:C:CC	acceptor_gain	1.0000
5:37125239:CT:C	donor_loss	1.0000
5:37125240:TT:T	donor_loss	1.0000
5:37125241:TACTG:T	donor_loss	1.0000
5:37125242:A:AC	donor_gain	1.0000
5:37125243:C:CG	donor_gain	1.0000
5:37125243:CTGG:C	donor_gain	1.0000
5:37125243:CTGGA:C	donor_gain	1.0000
5:37138715:ATTAC:A	donor_loss	1.0000
5:37138716:TTAC:T	donor_loss	1.0000
5:37138717:TACC:T	donor_loss	1.0000
5:37138718:A:C	donor_loss	1.0000
5:37138849:C:CC	acceptor_gain	1.0000
5:37138852:CATT:C	acceptor_gain	1.0000
5:37138855:T:TC	acceptor_gain	1.0000
5:37138858:CAAA:C	acceptor_gain	1.0000
5:37138859:A:T	acceptor_gain	1.0000
5:37138861:A:AC	acceptor_gain	1.0000
5:37138861:A:C	acceptor_gain	1.0000

AlphaMissense

21442 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:37206348:A:G	W1000R	0.998
5:37206348:A:T	W1000R	0.998
5:37187813:A:G	W1281R	0.996
5:37187813:A:T	W1281R	0.996
5:37247629:A:G	W24R	0.996
5:37247629:A:T	W24R	0.996
5:37187797:C:G	R1286P	0.995
5:37231024:A:G	W322R	0.994
5:37231024:A:T	W322R	0.994
5:37187444:G:C	S1350R	0.993
5:37187444:G:T	S1350R	0.993
5:37187446:T:G	S1350R	0.993
5:37187515:A:G	W1327R	0.993
5:37187515:A:T	W1327R	0.993
5:37198823:C:G	R1184P	0.993
5:37198824:G:T	R1184S	0.992
5:37226957:A:C	F546L	0.992
5:37226957:A:T	F546L	0.992
5:37226959:A:G	F546L	0.992
5:37230896:A:C	F364L	0.992
5:37230896:A:T	F364L	0.992
5:37230898:A:G	F364L	0.992
5:37187430:A:G	L1355P	0.991
5:37187442:A:G	L1351P	0.991
5:37183560:A:G	W1541R	0.990
5:37183560:A:T	W1541R	0.990
5:37187798:G:T	R1286S	0.990
5:37227689:C:T	G417E	0.990
5:37121744:C:G	A2966P	0.989
5:37121755:C:G	R2962P	0.989

dbSNP variants (sampled 300 via entrez): RS1000009787 (5:37210251 A>G), RS1000070597 (5:37151035 T>C), RS1000087633 (5:37116509 A>T), RS1000096868 (5:37199996 G>A), RS1000108096 (5:37163445 A>G), RS1000116922 (5:37247273 A>C,G), RS1000118681 (5:37098266 C>T), RS1000133904 (5:37140999 C>T), RS1000190349 (5:37158881 C>T), RS1000202690 (5:37196290 G>A), RS1000217896 (5:37122958 A>G), RS1000243355 (5:37193203 T>C), RS1000259290 (5:37076682 A>G), RS1000282761 (5:37101489 G>C,T), RS1000292805 (5:37122689 G>A)

Disease associations

OMIM: gene MIM:614571 | disease phenotypes: MIM:614615, MIM:277170, MIM:213300, MIM:616414, MIM:122470, MIM:256100, MIM:123100, MIM:613174, MIM:141200, MIM:603596

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 17	Definitive	Autosomal recessive
orofaciodigital syndrome type 6	Definitive	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Joubert syndrome 17	Definitive	AR

Mondo (17): Joubert syndrome 17 (MONDO:0013824), orofaciodigital syndrome type 6 (MONDO:0010176), Joubert syndrome 1 (MONDO:0008944), Joubert syndrome (MONDO:0018772), Joubert syndrome and related disorders (MONDO:0015369), autoimmune interstitial lung disease-arthritis syndrome (MONDO:0014629), cleft lip (MONDO:0004747), cleft palate (MONDO:0016064), astrocytoma (excluding glioblastoma) (MONDO:0019781), Cornelia de Lange syndrome 1 (MONDO:0007387), intellectual disability (MONDO:0001071), nephronophthisis (MONDO:0019005), focal segmental glomerulosclerosis (MONDO:0100313), craniosynostosis (MONDO:0015469), chromosome 5p13 duplication syndrome (MONDO:0013169)

Orphanet (10): Isolated Joubert syndrome (Orphanet:475), Orofaciodigital syndrome type 6 (Orphanet:2754), Joubert syndrome and related disorders (Orphanet:140874), Autoimmune interstitial lung disease-arthritis syndrome (Orphanet:444092), Cleft palate (Orphanet:2014), Cornelia de Lange syndrome (Orphanet:199), Nephronophthisis (Orphanet:655), Craniosynostosis (Orphanet:1531), 5p13 microduplication syndrome (Orphanet:329802), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

110 total (30 of 110 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000104	Renal agenesis
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000191	Accessory oral frenulum
HP:0000199	Tongue nodules
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000479	Abnormal retinal morphology
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000864	Abnormality of the hypothalamus-pituitary axis

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002437_2	Telomere length	3.000000e-06
GCST008839_146	Height	2.000000e-14
GCST010143_4	Meat-related diet	5.000000e-08
GCST010725_6	Malaria	9.000000e-07
GCST010725_66	Malaria	1.000000e-06
GCST010725_85	Malaria	5.000000e-06
GCST012335_6	Hodgkin’s lymphoma	4.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D001254	Astrocytoma	C04.557.465.625.600.380.080; C04.557.470.670.380.080; C04.557.580.625.600.380.080
D002971	Cleft Lip	C07.465.409.225; C07.465.525.164; C07.650.525.164; C16.131.850.525.164
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
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
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D017689	Polydactyly	C05.660.585.600; C16.131.621.585.600
C567717	Chromosome 5p13 Duplication Syndrome (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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance	2
Arsenic	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
glycidyl methacrylate	decreases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, decreases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Ozone	decreases expression, increases abundance, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Vanadates	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 4 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1PV	UNIBSi011-A	Induced pluripotent stem cell	Female
CVCL_A1PW	UNIBSi011-B	Induced pluripotent stem cell	Female
CVCL_A1PX	UNIBSi011-C	Induced pluripotent stem cell	Female
CVCL_D0NE	UNIPVi004-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03480607	PHASE4	COMPLETED	Dexmedetomidine as Adjuvant for Bupivacaine in Ultrasound Guided Infraorbital Nerve Block for Cleft Lip Repair
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT03314090	PHASE3	COMPLETED	Silicone Gel in the Treatment of Cleft Lip Scars
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00154375	PHASE3	COMPLETED	Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
NCT00335075	PHASE3	COMPLETED	Efficacy and Safety of Temodal vs Semustine in Subjects With Recurrent Glioblastoma or Anaplastic Astrocytoma (Study P03644)
NCT00897377	PHASE3	TERMINATED	Treatment Strategy for Low-grade Gliomas
NCT01649830	PHASE3	RECRUITING	Efficacy of Post-radiation Adjuvant Temozolomide Chemotherapy in Residue Low-grade Glioma
NCT01655927	PHASE3	UNKNOWN	Efficacy of Tranexamic Acid in Brain Tumor Resections
NCT03722355	PHASE3	COMPLETED	Hyperfractionated RT With BCNU Versus Conventional RT With BCNU for Supratentorial Malignant Glioma
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT06885801	PHASE2	NOT_YET_RECRUITING	Evaluation of a Novel Nasal Conformer in Pediatric Patients
NCT00760006	PHASE2	COMPLETED	Preventing Complications in Cleft Palate Repair With Antibiotics
NCT01760330	PHASE2	WITHDRAWN	IV Acetaminophen in Children Undergoing Palatoplasty
NCT02350803	PHASE2	COMPLETED	Does Use of Rigid Fixation After Removing Distraction Osteogenesis Device Reduce the Relapse?
NCT03412474	PHASE2	COMPLETED	Suprazygomatic Block in Cleft Palate Surgery in Children
NCT00165360	PHASE2	COMPLETED	Prolonged Daily Temozolomide for Low-Grade Glioma
NCT00179803	PHASE2	COMPLETED	Stem Cell Transplant for High Risk Central Nervous System (CNS) Tumors
NCT00360828	PHASE2	TERMINATED	Phase II Study of Irinotecan HCI for Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas
NCT00389090	PHASE2	TERMINATED	A Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
NCT00392171	PHASE2	COMPLETED	The Effects of Continuous 28-day (28/28) Temozolomide Chemotherapy in Subjects With Recurrent Malignant Glioma Who Have Failed the Conventional 5-day (5/28) Treatment (P04601)
NCT00575887	PHASE2	COMPLETED	Efficacy of Protracted Temozolomide in Patients With Progressive High Grade Glioma
NCT00782626	PHASE2	COMPLETED	Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
NCT00783393	PHASE2	COMPLETED	SCH 52365 Phase II Clinical Study: A Study on the Efficacy and Safety of Monotherapy With SCH 52365 in Patients With First Relapsed Anaplastic Astrocytoma (Study P03745)
NCT00921167	PHASE2	COMPLETED	A Study to Evaluate the Efficacy of Bevacizumab Plus Irinotecan in Recurrent Gliomas
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01351519	PHASE2	TERMINATED	A Study of Aminolevulinic Acid Used to Enhance Visualization and Surgical Removal of Brain Tumors