CEP104

Summary

CEP104 (centrosomal protein 104, HGNC:24866) is a protein-coding gene on chromosome 1p36.32, encoding Centrosomal protein of 104 kDa (O60308). Required for ciliogenesis and for structural integrity at the ciliary tip.

This gene encodes a centrosomal protein required for ciliogenesis and for ciliary tip structural integrity. The mammalian protein contains three amino-terminal hydrophobic domains, two glycosylation sites, four cysteine-rich motifs, and two regions with homology to the glutamate receptor ionotropic, NMDA 1 protein. During ciliogenesis, the encoded protein translocates from the distal tips of the centrioles to the tip of the elongating cilium. Knockdown of the protein in human retinal pigment cells results in severe defects in ciliogenesis with structural deformities at the ciliary tips. Allelic variants of this gene are associated with the autosomal-recessive disorder Joubert syndrome, which is characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia.

Source: NCBI Gene 9731 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 651 total — 20 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 49
• MANE Select transcript: NM_014704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24866
Approved symbol	CEP104
Name	centrosomal protein 104
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Aliases	GlyBP, RP1-286D6.4, CFAP256, ROC22, JBTS25
Ensembl gene	ENSG00000116198
Ensembl biotype	protein_coding
OMIM	616690
Entrez	9731

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 20 protein_coding, 7 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000378223, ENST00000378230, ENST00000428079, ENST00000438539, ENST00000460038, ENST00000461667, ENST00000484420, ENST00000494653, ENST00000495701, ENST00000674544, ENST00000674558, ENST00000674623, ENST00000674879, ENST00000674985, ENST00000675108, ENST00000675200, ENST00000675334, ENST00000675375, ENST00000675520, ENST00000675666, ENST00000675677, ENST00000675750, ENST00000675966, ENST00000676009, ENST00000676046, ENST00000676052, ENST00000894371, ENST00000894372, ENST00000894373, ENST00000923945, ENST00000923946, ENST00000923947, ENST00000955290, ENST00000955291

RefSeq mRNA: 1 — MANE Select: NM_014704 NM_014704

CCDS: CCDS30571

Canonical transcript exons

ENST00000378230 — 22 exons

Exon	Start	End
ENSE00001605351	3823174	3823241
ENSE00001675798	3823424	3823562
ENSE00001690217	3829266	3829373
ENSE00001711551	3829791	3829997
ENSE00001730754	3826708	3826744
ENSE00001761367	3825758	3825866
ENSE00001769704	3826370	3826436
ENSE00001786490	3831046	3831222
ENSE00001802822	3816280	3816370
ENSE00001928631	3812086	3815517
ENSE00001942582	3856889	3857211
ENSE00003562226	3833862	3834035
ENSE00003569347	3836495	3836692
ENSE00003577906	3847475	3847613
ENSE00003593231	3848608	3848781
ENSE00003594970	3845289	3845351
ENSE00003611334	3834925	3835092
ENSE00003624424	3852295	3852421
ENSE00003631373	3838964	3839119
ENSE00003632805	3839608	3839776
ENSE00003659383	3837292	3837519
ENSE00003665636	3844907	3844983

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 92.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6892 / max 77.9198, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9964	11.0041	1794
9965	0.6852	364

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.12	gold quality
buccal mucosa cell	CL:0002336	91.92	silver quality
sperm	CL:0000019	88.59	gold quality
medial globus pallidus	UBERON:0002477	88.27	gold quality
male germ cell	CL:0000015	88.03	gold quality
globus pallidus	UBERON:0001875	87.58	gold quality
saphenous vein	UBERON:0007318	87.56	gold quality
inferior vagus X ganglion	UBERON:0005363	87.41	gold quality
oocyte	CL:0000023	87.26	gold quality
islet of Langerhans	UBERON:0000006	87.12	gold quality
mammary duct	UBERON:0001765	87.01	gold quality
sural nerve	UBERON:0015488	86.57	gold quality
stromal cell of endometrium	CL:0002255	86.50	gold quality
epithelium of mammary gland	UBERON:0003244	86.37	gold quality
nipple	UBERON:0002030	85.94	gold quality
corpus callosum	UBERON:0002336	85.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.22	gold quality
blood vessel layer	UBERON:0004797	85.08	gold quality
subthalamic nucleus	UBERON:0001906	85.03	gold quality
left testis	UBERON:0004533	84.90	gold quality
hair follicle	UBERON:0002073	84.86	silver quality
right adrenal gland cortex	UBERON:0035827	84.74	gold quality
pons	UBERON:0000988	84.72	gold quality
cranial nerve II	UBERON:0000941	84.70	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.70	gold quality
popliteal artery	UBERON:0002250	84.55	gold quality
tibial artery	UBERON:0007610	84.53	gold quality
spinal cord	UBERON:0002240	84.51	gold quality
testis	UBERON:0000473	84.47	gold quality
right adrenal gland	UBERON:0001233	84.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.59
E-GEOD-137537	yes	5.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting CEP104, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-383-3P	99.85	65.84	1359

Literature-anchored findings (GeneRIF, showing 5)

• Mutations in CEP104 is associated with Joubert Syndrome. (PMID:26477546)
• Biophysical and Structural Characterization of the Centriolar Protein Cep104 Interaction Network. (PMID:27402853)
• Study identified two novel heterozygous mutations of CEP104 in a patient with Joubert syndrome, which were c.2364+1G>A and c.414delC (p.Asn138Lysfs*11) and consistent with the autosomal recessive inheritance mode. (PMID:31625690)
• Roles of TOG and jelly-roll domains of centrosomal protein CEP104 in its functions in cilium elongation and Hedgehog signaling. (PMID:32820051)
• CEP104 and CEP290; Genes with Ciliary Functions Cause Intellectual Disability in Multiple Families. (PMID:34196201)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep104	ENSDARG00000060361
mus_musculus	Cep104	ENSMUSG00000039523
rattus_norvegicus	Cep104	ENSRNOG00000025000
drosophila_melanogaster	CG10137	FBGN0032800
caenorhabditis_elegans		WBGENE00008039
caenorhabditis_elegans		WBGENE00009208
caenorhabditis_elegans		WBGENE00011523
caenorhabditis_elegans		WBGENE00015517

Protein

Protein identifiers

Centrosomal protein of 104 kDa — O60308 (reviewed: O60308)

All UniProt accessions (13): A0A6Q8PFR4, A0A6Q8PG89, A0A6Q8PGB3, A0A6Q8PGF0, A0A6Q8PGQ7, A0A6Q8PH14, A0A6Q8PH38, A0A6Q8PH69, A0A6Q8PHE1, A0A6Q8PHR0, O60308, J3QLL3, Q5SR27

UniProt curated annotations — full annotation on UniProt →

Function. Required for ciliogenesis and for structural integrity at the ciliary tip.

Subunit / interactions. Interacts with CCP110 and CEP97. Interacts with ARMC9, TOGARAM1, CCDC66 and CSPP1.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Spindle pole.

Disease relevance. Joubert syndrome 25 (JBTS25) [MIM:616781] A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS25 clinical manifestations appear to be confined to the neurologic system. JBTS25 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, autosomal recessive 77 (MRT77) [MIM:619988] An autosomal recessive neurodevelopmental disorder apparent from infancy and characterized by global developmental delay, variably impaired cognitive development, delayed walking, and poor speech in some cases. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
O60308-1	1	yes
O60308-2	2
O60308-3	3

RefSeq proteins (1): NP_055519* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR034085	TOG	Domain
IPR048738	CEP104_Znf	Domain
IPR048739	CEP104_N	Domain
IPR052607	CEP104-like	Family

Pfam: PF21038, PF21039, PF21040

UniProt features (55 total): helix 25, turn 7, strand 6, splice variant 4, sequence variant 3, sequence conflict 3, repeat 2, coiled-coil region 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5LPI	X-RAY DIFFRACTION	1.8
5LPH	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60308-F1	76.75	0.51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, AMIT_EGF_RESPONSE_120_HELA, GOCC_CENTROSOME, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOCC_SPINDLE, GOCC_CENTRIOLE, GOCC_CILIUM, chr1p36, DAVICIONI_MOLECULAR_ARMS_VS_ERMS_UP, ARID5B_TARGET_GENES, ATF6_TARGET_GENES, CHAF1B_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (7): spindle pole (GO:0000922), centrosome (GO:0005813), centriole (GO:0005814), cilium (GO:0005929), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule organizing center	2
intracellular membraneless organelle	2
binding	1
spindle	1
centriole	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP104	CCP110	O43303	840
CEP104	CEP97	Q8IW35	808
CEP104	KATNIP	O60303	690
CEP104	CEP290	O15078	657
CEP104	CEP89	Q96ST8	594
CEP104	CSPP1	Q1MSJ5	572
CEP104	TOGARAM1	Q9Y4F4	544
CEP104	CEP128	Q6ZU80	539
CEP104	CPAP	Q9HC77	528
CEP104	C1orf174	Q8IYL3	506
CEP104	TTBK2	Q6IQ55	503
CEP104	KIF24	Q5T7B8	501
CEP104	PDE6D	O43924	491
CEP104	RAB8A	P24407	490
CEP104	CCDC27	Q2M243	481

IntAct

28 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
CEP104	TOGARAM1	psi-mi:“MI:0915”(physical association)	0.540
CEP104	CSPP1	psi-mi:“MI:0915”(physical association)	0.540
CEP104	CCDC66	psi-mi:“MI:0915”(physical association)	0.540
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
CEP104	RRBP1	psi-mi:“MI:0915”(physical association)	0.400
CEP104	PPP1R13B	psi-mi:“MI:0915”(physical association)	0.400
CEP104	VSIG8	psi-mi:“MI:0915”(physical association)	0.400
CEP104	ARMC9	psi-mi:“MI:0915”(physical association)	0.400
CEP104	CEP104	psi-mi:“MI:0915”(physical association)	0.400
Sgo2a	GPA33	psi-mi:“MI:0914”(association)	0.350
WASHC3	WASHC1	psi-mi:“MI:0914”(association)	0.350
CEP162	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SF1	CEP104	psi-mi:“MI:0915”(physical association)	0.000
CEP104	SF1	psi-mi:“MI:0915”(physical association)	0.000
CEP104	NR2F6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (95): CEP104 (Proximity Label-MS), ADSL (Proximity Label-MS), AHCY (Proximity Label-MS), ALMS1 (Proximity Label-MS), AP4E1 (Proximity Label-MS), AP4S1 (Proximity Label-MS), APBB1 (Proximity Label-MS), ARPC3 (Proximity Label-MS), CEP131 (Proximity Label-MS), C21orf2 (Proximity Label-MS), CACYBP (Proximity Label-MS), CALM2 (Proximity Label-MS), CAMSAP1 (Proximity Label-MS), CAMSAP2 (Proximity Label-MS), CC2D1A (Proximity Label-MS)

ESM2 similar proteins: A0A0G2JV04, B0V207, D3Z8X7, D3ZFJ3, D3ZND0, F1LM81, G9CGD6, O00499, O08539, O08839, O12940, O60308, O60784, O75674, O88746, P42567, P55194, Q05DH4, Q0GNC1, Q0IHV1, Q27J81, Q3B7M3, Q3UN70, Q4KLN4, Q505K2, Q5FVK6, Q5T0F9, Q5U3K5, Q66HA5, Q68EF0, Q6P1N0, Q6P5E6, Q6P9Q4, Q6P9Q6, Q80V31, Q80V94, Q8BMI3, Q8BRN9, Q8K1A6, Q8R0H9

Diamond homologs: D3Z8X7, O60308, Q80V31

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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.

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	5	20.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	22
Uncertain significance	210
Likely benign	201
Benign	129

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1322057	NM_014704.4(CEP104):c.2081_2084del (p.Gln694fs)	Pathogenic
1700579	NM_014704.4(CEP104):c.2356_2357insTT (p.Cys786fs)	Pathogenic
1700580	NM_014704.4(CEP104):c.1901dup (p.Leu634fs)	Pathogenic
1700581	NM_014704.4(CEP104):c.643C>T (p.Arg215Ter)	Pathogenic
221274	NM_014704.4(CEP104):c.735+2T>C	Pathogenic
221275	NM_014704.4(CEP104):c.1328_1329insT (p.Tyr444fs)	Pathogenic
221276	NM_014704.4(CEP104):c.496C>T (p.Arg166Ter)	Pathogenic
221277	NM_014704.4(CEP104):c.2572-2A>G	Pathogenic
2691290	NM_014704.4(CEP104):c.1232del (p.Gly411fs)	Pathogenic
2893140	NC_000001.11:g.3823227_3823243del	Pathogenic
3004548	NM_014704.4(CEP104):c.1745del (p.His582fs)	Pathogenic
3360460	NM_014704.4(CEP104):c.48del (p.Asp17fs)	Pathogenic
3629940	NM_014704.4(CEP104):c.2364+1G>A	Pathogenic
3646990	NM_014704.4(CEP104):c.157A>T (p.Arg53Ter)	Pathogenic
4526232	NM_014704.4(CEP104):c.2080_2083del (p.Gln694fs)	Pathogenic
4700540	NM_014704.4(CEP104):c.1351C>T (p.Arg451Ter)	Pathogenic
4812090	NM_014704.4(CEP104):c.1031del (p.Lys344fs)	Pathogenic
542193	NM_014704.4(CEP104):c.1082_1091del (p.Pro361fs)	Pathogenic
665628	NC_000001.11:g.(?3815382)(3852427_?)del	Pathogenic
812756	NM_014704.4(CEP104):c.89del (p.Thr30fs)	Pathogenic
1677239	NM_014704.4(CEP104):c.1867_1870del (p.Tyr623fs)	Likely pathogenic
1704568	NM_014704.4(CEP104):c.2286del (p.Glu762fs)	Likely pathogenic
1723240	NM_014704.4(CEP104):c.928dup (p.Ala310fs)	Likely pathogenic
1723276	NM_014704.4(CEP104):c.162T>A (p.Cys54Ter)	Likely pathogenic
1723370	NM_014704.4(CEP104):c.182del (p.Leu61fs)	Likely pathogenic
1878385	NM_014704.4(CEP104):c.1485+1G>A	Likely pathogenic
2429931	NM_014704.4(CEP104):c.1241T>A (p.Leu414Ter)	Likely pathogenic
2633413	NM_014704.4(CEP104):c.1561G>T (p.Glu521Ter)	Likely pathogenic
3356604	NM_014704.4(CEP104):c.2656C>T (p.Gln886Ter)	Likely pathogenic
3583673	NM_014704.4(CEP104):c.2365-2A>G	Likely pathogenic

SpliceAI

4027 predictions. Top by Δscore:

Variant	Effect	Δscore
1:3815518:C:CC	acceptor_gain	1.0000
1:3816277:CA:C	donor_loss	1.0000
1:3816278:A:C	donor_loss	1.0000
1:3816279:C:CT	donor_loss	1.0000
1:3816279:CCTGG:C	donor_gain	1.0000
1:3816366:CATGC:C	acceptor_gain	1.0000
1:3816368:TGC:T	acceptor_gain	1.0000
1:3816369:GCCT:G	acceptor_loss	1.0000
1:3816370:CCTG:C	acceptor_loss	1.0000
1:3816371:C:CA	acceptor_loss	1.0000
1:3816371:C:CC	acceptor_gain	1.0000
1:3816377:C:CT	acceptor_gain	1.0000
1:3816378:A:T	acceptor_gain	1.0000
1:3823422:A:AC	donor_gain	1.0000
1:3823423:C:CA	donor_gain	1.0000
1:3823423:CG:C	donor_gain	1.0000
1:3823423:CGG:C	donor_gain	1.0000
1:3823571:C:CT	acceptor_gain	1.0000
1:3825293:T:A	donor_gain	1.0000
1:3826368:A:AC	donor_gain	1.0000
1:3826369:C:CC	donor_gain	1.0000
1:3826369:CTTAT:C	donor_gain	1.0000
1:3826373:T:C	donor_gain	1.0000
1:3829257:A:C	donor_gain	1.0000
1:3829265:C:A	donor_loss	1.0000
1:3829266:C:G	donor_loss	1.0000
1:3829374:C:CA	acceptor_loss	1.0000
1:3829374:C:CC	acceptor_gain	1.0000
1:3829375:T:A	acceptor_loss	1.0000
1:3831040:GCTTA:G	donor_loss	1.0000

AlphaMissense

6076 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:3825793:A:G	C777R	1.000
1:3852308:A:G	W34R	1.000
1:3852308:A:T	W34R	1.000
1:3823212:A:G	C845R	0.999
1:3825775:A:G	C783R	0.999
1:3825783:A:G	L780P	0.999
1:3825791:A:C	C777W	0.999
1:3825792:C:T	C777Y	0.999
1:3825854:A:C	F756L	0.999
1:3825854:A:T	F756L	0.999
1:3825856:A:G	F756L	0.999
1:3825860:A:C	C754W	0.999
1:3825861:C:G	C754S	0.999
1:3825862:A:G	C754R	0.999
1:3825862:A:T	C754S	0.999
1:3847563:A:G	L113P	0.999
1:3816322:G:T	R874S	0.998
1:3816337:A:G	C869R	0.998
1:3816367:A:G	W859R	0.998
1:3816367:A:T	W859R	0.998
1:3823202:C:G	C848S	0.998
1:3823203:A:G	C848R	0.998
1:3823203:A:T	C848S	0.998
1:3823211:C:G	C845S	0.998
1:3823212:A:T	C845S	0.998
1:3823520:A:G	C803R	0.998
1:3823533:G:C	H798Q	0.998
1:3823533:G:T	H798Q	0.998
1:3825783:A:T	L780Q	0.998
1:3825792:C:A	C777F	0.998

dbSNP variants (sampled 300 via entrez): RS1000008321 (1:3846278 T>A), RS1000010163 (1:3840202 C>T), RS1000064390 (1:3840338 G>T), RS1000080745 (1:3855717 C>T), RS1000082559 (1:3818446 G>A), RS1000102654 (1:3857280 T>A,C), RS1000297312 (1:3829642 C>A,G,T), RS1000359735 (1:3846011 A>G), RS1000367042 (1:3830067 G>C,T), RS1000437389 (1:3830224 G>A), RS1000514058 (1:3857163 C>T), RS1000530193 (1:3820001 G>C,T), RS1000546707 (1:3824436 G>A), RS1000565135 (1:3856977 C>CG), RS1000603020 (1:3819419 C>T)

Disease associations

OMIM: gene MIM:616690 | disease phenotypes: MIM:616781, MIM:619988, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 25	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
ciliopathy	Definitive	AR

Mondo (8): Joubert syndrome 25 (MONDO:0014770), Joubert syndrome and related disorders (MONDO:0015369), intellectual developmental disorder, autosomal recessive 77 (MONDO:0031031), autism spectrum disorder (MONDO:0005258), Joubert syndrome (MONDO:0018772), cerebellar ataxia (MONDO:0000437), dystonic disorder (MONDO:0003441), ciliopathy (MONDO:0005308)

Orphanet (5): Isolated Joubert syndrome (Orphanet:475), Joubert syndrome and related disorders (Orphanet:140874), Rare ataxia (Orphanet:102002), Ciliopathy (Orphanet:363250), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000512	Abnormal electroretinogram
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0001058	Poor wound healing
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001337	Tremor
HP:0001382	Joint hypermobility
HP:0001611	Hypernasal speech
HP:0001696	Situs inversus totalis
HP:0001829	Foot polydactyly

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002041_1	Blood trace element (Cu levels)	5.000000e-10
GCST004602_2	Mean corpuscular volume	1.000000e-13
GCST008398_7	Glycated hemoglobin levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005267	serum copper measurement
EFO:0004541	HbA1c measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D020821	Dystonic Disorders	C10.228.662.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression, increases expression	4
Benzo(a)pyrene	affects methylation	2
Particulate Matter	increases abundance, increases expression, affects expression	2
aristolochic acid I	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
avobenzone	increases expression	1
K 7174	increases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	affects expression, increases abundance	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder