CEP41

Summary

CEP41 (centrosomal protein 41, HGNC:12370) is a protein-coding gene on chromosome 7q32.2, encoding Centrosomal protein of 41 kDa (Q9BYV8). Required during ciliogenesis for tubulin glutamylation in cilium.

This gene encodes a centrosomal and microtubule-binding protein which is predicted to have two coiled-coil domains and a rhodanese domain. In human retinal pigment epithelial cells the protein localized to centrioles and cilia. Mutations in this gene have been associated with Joubert Syndrome 15; an autosomal recessive ciliopathy and neurological disorder. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 95681 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 15 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 489 total — 16 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 56
• MANE Select transcript: NM_018718

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12370
Approved symbol	CEP41
Name	centrosomal protein 41
Location	7q32.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp762H1311, FLJ22445, JBTS15
Ensembl gene	ENSG00000106477
Ensembl biotype	protein_coding
OMIM	610523
Entrez	95681

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 23 protein_coding, 7 nonsense_mediated_decay, 5 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000223208, ENST00000334451, ENST00000343969, ENST00000469826, ENST00000471201, ENST00000472739, ENST00000475282, ENST00000477003, ENST00000480206, ENST00000482730, ENST00000484549, ENST00000485736, ENST00000489512, ENST00000492389, ENST00000498527, ENST00000541543, ENST00000603513, ENST00000674539, ENST00000674630, ENST00000675138, ENST00000675168, ENST00000675328, ENST00000675494, ENST00000675542, ENST00000675563, ENST00000675596, ENST00000675626, ENST00000675649, ENST00000675721, ENST00000675803, ENST00000675813, ENST00000675935, ENST00000675962, ENST00000676115, ENST00000676243, ENST00000676312, ENST00000934756, ENST00000934757

RefSeq mRNA: 4 — MANE Select: NM_018718 NM_001257158, NM_001257159, NM_001257160, NM_018718

CCDS: CCDS5821, CCDS59078, CCDS59079, CCDS59080

Canonical transcript exons

ENST00000223208 — 11 exons

Exon	Start	End
ENSE00000723269	130393771	130399039
ENSE00001039832	130404564	130404708
ENSE00001868132	130440934	130441016
ENSE00003502438	130427955	130428018
ENSE00003557671	130412179	130412240
ENSE00003608755	130400707	130400821
ENSE00003649520	130411122	130411191
ENSE00003649764	130401881	130401948
ENSE00003691945	130416919	130416966
ENSE00003692578	130400039	130400254
ENSE00003693689	130402648	130402799

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 93.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8539 / max 177.2784, expressed in 1693 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86155	8.6076	1689
86156	0.0760	14
86154	0.0564	21
86150	0.0429	17
86151	0.0222	8
86149	0.0192	5
86152	0.0165	4
86157	0.0131	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.33	gold quality
left testis	UBERON:0004533	93.13	gold quality
right testis	UBERON:0004534	92.89	gold quality
secondary oocyte	CL:0000655	92.76	gold quality
endothelial cell	CL:0000115	92.30	silver quality
male germ cell	CL:0000015	91.04	gold quality
testis	UBERON:0000473	90.78	gold quality
middle temporal gyrus	UBERON:0002771	90.15	gold quality
bronchial epithelial cell	CL:0002328	89.86	gold quality
oocyte	CL:0000023	89.13	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.77	gold quality
ganglionic eminence	UBERON:0004023	85.98	gold quality
cortical plate	UBERON:0005343	85.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.79	gold quality
epithelium of bronchus	UBERON:0002031	85.76	gold quality
bronchus	UBERON:0002185	85.28	gold quality
saliva-secreting gland	UBERON:0001044	84.80	gold quality
parotid gland	UBERON:0001831	84.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.57	gold quality
ventricular zone	UBERON:0003053	83.93	gold quality
minor salivary gland	UBERON:0001830	83.69	gold quality
islet of Langerhans	UBERON:0000006	83.25	gold quality
primary visual cortex	UBERON:0002436	82.44	gold quality
pigmented layer of retina	UBERON:0001782	81.79	gold quality
retina	UBERON:0000966	81.77	gold quality
right uterine tube	UBERON:0001302	81.09	gold quality
mouth mucosa	UBERON:0003729	80.67	gold quality
occipital lobe	UBERON:0002021	80.54	gold quality
prefrontal cortex	UBERON:0000451	80.49	gold quality
stromal cell of endometrium	CL:0002255	79.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	11.08
E-ANND-3	yes	6.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

189 targeting CEP41, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821

Literature-anchored findings (GeneRIF, showing 5)

• Three rare potentially pathogenic variants were identified in the TSGA14 gene, which encodes a centrosomal protein. (PMID:21438139)
• The data identified CEP41 mutations as a cause of Joubert syndrome and implicated tubulin post-translational modification in the pathogenesis of human ciliary dysfunction. (PMID:22246503)
• In cortices, the MEST promoter was hemimethylated, as expected for a differentially methylated imprinting control region, whereas the COPG2 and TSGA14 promoters were completely demethylated, typical for transcriptionally active non-imprinted genes. (PMID:22456293)
• Missense variants in one gene, CEP41, associated significantly with Autism Spectrum Disorder (ASD). Homozygous gene-disrupting variants in CEP41 were initially found to be responsible for recessive Joubert syndrome. (PMID:30664616)
• CEP41-mediated ciliary tubulin glutamylation drives angiogenesis through AURKA-dependent deciliation. (PMID:31885126)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep41	ENSDARG00000038500
mus_musculus	Cep41	ENSMUSG00000029790
rattus_norvegicus	Cep41	ENSRNOG00000010950

Paralogs (1): TSTD1 (ENSG00000215845)

Protein

Protein identifiers

Centrosomal protein of 41 kDa — Q9BYV8 (reviewed: Q9BYV8)

Alternative names: Testis-specific gene A14 protein

All UniProt accessions (20): Q9BYV8, A0A6Q8PEV5, A0A6Q8PF12, A0A6Q8PFB1, A0A6Q8PFB5, A0A6Q8PFZ2, A0A6Q8PG60, A0A6Q8PGR4, A0A6Q8PGX0, A0A6Q8PH03, A0A6Q8PH12, A0A6Q8PH93, A0A6Q8PHU1, A0A7I2PK71, A0A7I2SYM4, C9IZ34, C9J6R3, C9JCX6, C9JXA0, F8WAV3

UniProt curated annotations — full annotation on UniProt →

Function. Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of TTLL6, a tubulin polyglutamylase, between the basal body and the cilium.

Subunit / interactions. Found in a complex with TTLL6.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cell projection. Cilium. Cilium basal body.

Tissue specificity. Expressed in testis and fetal tissues. Expressed in testis and fetal tissues.

Disease relevance. Joubert syndrome 15 (JBTS15) [MIM:614464] An autosomal recessive 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. Genetic variations in CEP41 may be associated with susceptibility to autism.

Domain organisation. Although it contains a rhodanese domain, does not display phosphatase activity, suggesting that the protein is enzymatically inactive.

Similarity. Belongs to the CEP41 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BYV8-1	1, L-type	yes
Q9BYV8-2	2
Q9BYV8-4	3, S-type
Q9BYV8-5	4

RefSeq proteins (4): NP_001244087, NP_001244088, NP_001244089, NP_061188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001763	Rhodanese-like_dom	Domain
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily
IPR051889	CEP41	Family

Pfam: PF00581

UniProt features (24 total): sequence variant 6, modified residue 5, splice variant 4, compositionally biased region 3, region of interest 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYV8-F1	71.06	0.28

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 (5): 121, 343, 96, 99, 109

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 319 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, RNGTGGGC_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, NKX25_02, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, EFC_Q6, CEBPB_01, CEBP_Q2, MODULE_205, MYOD_01, GOBP_CILIUM_ORGANIZATION, chr7q32

GO Biological Process (4): protein transport (GO:0015031), protein polyglutamylation (GO:0018095), cilium assembly (GO:0060271), cell projection organization (GO:0030030)

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

GO Cellular Component (9): centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cilium (GO:0005929), membrane (GO:0016020), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1
M Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule organizing center	3
intracellular membraneless organelle	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
peptidyl-glutamic acid modification	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
centriole	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP41	MEST	Q5EB52	874
CEP41	TTLL6	Q8N841	860
CEP41	TCTN1	Q2MV58	689
CEP41	TMEM237	Q96Q45	684
CEP41	TCTN3	Q6NUS6	683
CEP41	TMEM216	Q9P0N5	670
CEP41	CPLANE1	Q9H799	665
CEP41	TMEM138	Q9NPI0	662
CEP41	CC2D2A	Q9P2K1	657
CEP41	TTLL1	O95922	643
CEP41	AHI1	Q8N157	641
CEP41	TMEM67	Q5HYA8	634
CEP41	ARL13B	Q3SXY8	633
CEP41	KIF7	Q2M1P5	624
CEP41	B9D1	Q9UPM9	616

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CEP41	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CERS2	VPS37C	psi-mi:“MI:0914”(association)	0.350
CEP41	ATP12A	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
DCTN1	NACA	psi-mi:“MI:2364”(proximity)	0.270
TUBA1A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (32): HIP1R (Co-fractionation), MVB12A (Co-fractionation), WARS (Co-fractionation), CEP41 (Proximity Label-MS), CEP41 (Affinity Capture-MS), CEP41 (Proximity Label-MS), CEP41 (Synthetic Lethality), CEP41 (Proximity Label-MS), CEP41 (Proximity Label-MS), CEP41 (Proximity Label-MS), CEP41 (Proximity Label-MS), CEP41 (Affinity Capture-MS), CEP41 (Proximity Label-MS), CEP41 (Proximity Label-MS), CEP41 (Proximity Label-MS)

ESM2 similar proteins: A0JPH7, A1A5Q0, B0R034, E1BTG2, E1C065, E1C760, F1MUG2, F7AEX0, G3XA57, O60308, P30306, P48966, Q02225, Q0IID7, Q0VBD2, Q14B46, Q28E45, Q28FA8, Q3UHZ5, Q4KM37, Q5EAW4, Q5FWH3, Q5JTW2, Q5RHY1, Q5XGX5, Q60949, Q6GQN0, Q6INA9, Q6NTY8, Q6NU40, Q6P5Q4, Q7L590, Q80U87, Q8BN58, Q8BXR9, Q8BZN6, Q8C5W4, Q8GT06, Q8K3X6, Q8N8V4

Diamond homologs: A0JPH7, E1C065, F1MUG2, Q28FA8, Q4KM37, Q6GQN0, Q6NTY8, Q99NF3, Q9BYV8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CEP41	“up-regulates activity”	HIF1A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	6
Uncertain significance	253
Likely benign	141
Benign	29

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1029717	NM_018718.3(CEP41):c.34-2A>G	Pathogenic
1457092	NM_018718.3(CEP41):c.7del (p.Leu3fs)	Pathogenic
2131693	NM_018718.3(CEP41):c.477del (p.Glu160fs)	Pathogenic
2308063	NM_018718.3(CEP41):c.33+1G>A	Pathogenic
2740806	NM_018718.3(CEP41):c.880del (p.Leu294fs)	Pathogenic
280165	NM_018718.3(CEP41):c.418C>T (p.Gln140Ter)	Pathogenic
30838	NM_018718.3(CEP41):c.33+2T>G	Pathogenic
30839	NM_018718.3(CEP41):c.97+3_97+5del	Pathogenic
30840	NM_018718.3(CEP41):c.423-2A>C	Pathogenic
30844	NM_018718.3(CEP41):c.83C>A (p.Ser28Ter)	Pathogenic
3621567	NM_018718.3(CEP41):c.55C>T (p.Gln19Ter)	Pathogenic
3650399	NM_018718.3(CEP41):c.542_545del (p.Arg181fs)	Pathogenic
3708774	NM_018718.3(CEP41):c.156del (p.Arg51_Tyr52insTer)	Pathogenic
4725805	NM_018718.3(CEP41):c.313_314dup (p.Thr106fs)	Pathogenic
4839576	NM_018718.3(CEP41):c.162del (p.Asp55fs)	Pathogenic
954659	NM_018718.3(CEP41):c.423-2A>G	Pathogenic
1471398	NM_018718.3(CEP41):c.278-1G>A	Likely pathogenic
1958588	NM_018718.3(CEP41):c.757+2T>A	Likely pathogenic
2752461	NM_018718.3(CEP41):c.98-2A>G	Likely pathogenic
4739999	NM_018718.3(CEP41):c.643-1G>A	Likely pathogenic
692046	NM_018718.3(CEP41):c.942_943del (p.Glu315fs)	Likely pathogenic
982170	NM_018718.3(CEP41):c.602C>G (p.Ser201Cys)	Likely pathogenic

SpliceAI

2485 predictions. Top by Δscore:

Variant	Effect	Δscore
7:130402798:CA:C	acceptor_gain	1.0000
7:130402800:C:CC	acceptor_gain	1.0000
7:130404716:T:C	acceptor_gain	1.0000
7:130411116:CATTA:C	donor_loss	1.0000
7:130411118:TTAC:T	donor_loss	1.0000
7:130411119:TA:T	donor_loss	1.0000
7:130416917:A:AC	donor_gain	1.0000
7:130416918:C:CC	donor_gain	1.0000
7:130416918:CTTTT:C	donor_gain	1.0000
7:130427947:TTAC:T	donor_loss	1.0000
7:130427948:TACT:T	donor_loss	1.0000
7:130427949:ACT:A	donor_loss	1.0000
7:130427951:TCACC:T	donor_loss	1.0000
7:130427952:C:CC	donor_loss	1.0000
7:130427953:A:AC	donor_gain	1.0000
7:130427954:C:A	donor_loss	1.0000
7:130427954:C:CC	donor_gain	1.0000
7:130428014:AGATA:A	acceptor_gain	1.0000
7:130428015:GATA:G	acceptor_gain	1.0000
7:130428016:ATA:A	acceptor_gain	1.0000
7:130428016:ATAC:A	acceptor_loss	1.0000
7:130428017:TA:T	acceptor_gain	1.0000
7:130428018:ACTA:A	acceptor_loss	1.0000
7:130428019:C:CC	acceptor_gain	1.0000
7:130428019:C:T	acceptor_loss	1.0000
7:130428020:T:G	acceptor_loss	1.0000
7:130398896:T:TA	donor_gain	0.9900
7:130400873:C:CC	acceptor_gain	0.9900
7:130402642:TCTTA:T	donor_loss	0.9900
7:130402643:CTTA:C	donor_loss	0.9900

AlphaMissense

2434 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:130400739:C:G	R242P	0.999
7:130400726:G:C	N246K	0.998
7:130400726:G:T	N246K	0.998
7:130400757:G:T	A236D	0.998
7:130401917:T:A	R202S	0.998
7:130401917:T:G	R202S	0.998
7:130402701:A:G	L174P	0.998
7:130412180:A:G	L69P	0.998
7:130400740:G:T	R242S	0.997
7:130400769:G:T	A232D	0.997
7:130400819:T:A	K215N	0.997
7:130400819:T:G	K215N	0.997
7:130401918:C:G	R202T	0.997
7:130402695:A:G	L176P	0.997
7:130412206:T:A	R60S	0.997
7:130412206:T:G	R60S	0.997
7:130412212:G:C	F58L	0.997
7:130412212:G:T	F58L	0.997
7:130412214:A:G	F58L	0.997
7:130400758:C:G	A236P	0.996
7:130412186:G:T	A67D	0.996
7:130412204:A:G	L61P	0.996
7:130412207:C:G	R60T	0.996
7:130400715:A:T	L250H	0.995
7:130400796:A:T	I223N	0.995
7:130412213:A:G	F58S	0.995
7:130400720:G:C	F248L	0.994
7:130400720:G:T	F248L	0.994
7:130400722:A:G	F248L	0.994
7:130400799:A:T	I222N	0.994

dbSNP variants (sampled 300 via entrez): RS1000209447 (7:130417812 T>C), RS1000334928 (7:130395988 T>C), RS1000392753 (7:130402922 A>G), RS1000405686 (7:130403155 G>A), RS1000467945 (7:130436542 T>C), RS1000545405 (7:130416191 C>T), RS1000719279 (7:130410273 C>T), RS1000725337 (7:130400933 T>A,C), RS1000779769 (7:130429782 C>T), RS1000984278 (7:130408195 C>A), RS1001041856 (7:130423562 T>C,G), RS1001141841 (7:130415834 T>C), RS1001210268 (7:130419539 T>C), RS1001408897 (7:130405037 C>T), RS1001410860 (7:130423109 G>T)

Disease associations

OMIM: gene MIM:610523 | disease phenotypes: MIM:614464, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 15	Definitive	Autosomal recessive
Joubert syndrome with ocular defect	Supportive	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliopathy	Strong	AR

Mondo (4): Joubert syndrome 15 (MONDO:0013763), intellectual disability (MONDO:0001071), Joubert syndrome (MONDO:0018772), Joubert syndrome with ocular defect (MONDO:0016364)

Orphanet (2): Isolated Joubert syndrome (Orphanet:475), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000090	Nephronophthisis
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000480	Retinal coloboma
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000508	Ptosis
HP:0000556	Retinal dystrophy
HP:0000572	Visual loss
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004987_7	Antipsychotic drug-induced QTc interval change in schizophrenia	9.000000e-07
GCST005958_14	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-07
GCST005962_34	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST010463_14	Childhood ALL/LBL (acute lymphoblastic leukemia/lymphoblastic lymphoma) treatment-related venous thromboembolism	2.000000e-06
GCST90020026_602	Hip index	5.000000e-11
GCST90020026_603	Hip index	6.000000e-15
GCST90020026_604	Hip index	1.000000e-13
GCST90020026_605	Hip index	3.000000e-09
GCST90020028_278	Hip circumference adjusted for BMI	1.000000e-08
GCST90020028_279	Hip circumference adjusted for BMI	3.000000e-12
GCST90020028_280	Hip circumference adjusted for BMI	7.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008003	heart rate variability measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Valproic Acid	affects expression, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	affects methylation	1
cobaltous chloride	affects expression, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	decreases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	affects expression	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
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
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
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)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)