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): 719 total — 18 pathogenic, 28 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 45 tissues, sQTL in 26 (q < 0.05)
• Phenotypes (HPO): 49
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.85 (unconstrained)
• 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: 42 — 24 protein_coding, 9 nonsense_mediated_decay, 7 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000378230

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 1, TSL 5: 4

ENST00000378230, ENST00000378223, 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, ENST00000998465, ENST00000998466, ENST00001055583, ENST00001055584, ENST00001111342, ENST00001111343, ENST00001114137, ENST00001144654

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.

Highest expression (Bgee): secondary oocyte, buccal mucosa cell, sperm, medial globus pallidus, male germ cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CEP104 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 26 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 71 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	6.6e-87	+0.50	1:3845512:T:C
Skin Sun Exposed Lower leg	eqtl	2.9e-81	-0.46	1:3827984:A:G
Thyroid	eqtl	1.7e-78	+0.54	1:3856688:C:A
Whole Blood	eqtl	4.6e-75	+0.53	1:3834165:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-63	+0.44	1:3833651:AC:A
Adipose Subcutaneous	eqtl	1.4e-57	+0.38	1:3843497:G:A
Adrenal Gland	eqtl	8.5e-48	+0.78	1:3852155:T:C
Lung	eqtl	2.7e-43	-0.28	1:3827984:A:G
Esophagus Mucosa	eqtl	6.9e-43	+0.44	1:3856688:C:A
Pancreas	eqtl	1.8e-41	-0.76	1:3852469:A:T
Testis	eqtl	4.6e-37	+0.51	1:3857985:C:T
Breast Mammary Tissue	eqtl	7.5e-36	+0.37	1:3856688:C:A
Adipose Visceral Omentum	eqtl	2.2e-35	+0.33	1:3833651:AC:A
Cells Cultured fibroblasts	eqtl	1.0e-32	+0.29	1:3856688:C:A
Artery Tibial	eqtl	1.2e-27	-0.18	1:3857566:A:G
Colon Transverse	eqtl	2.4e-26	-0.37	1:3788457:T:C
Artery Aorta	eqtl	1.6e-25	-0.30	1:3806639:T:C
Spleen	eqtl	2.5e-24	+0.53	1:3831016:C:T
Cells EBV-transformed lymphocytes	eqtl	2.8e-23	-0.60	1:3852469:A:T
Stomach	eqtl	2.2e-22	-0.33	1:3826755:G:A

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 294 tissues 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
adrenal cortex	UBERON:0001235	84.44	gold quality
left adrenal gland cortex	UBERON:0035825	84.43	gold quality
left adrenal gland	UBERON:0001234	84.35	gold quality
monocyte	CL:0000576	84.33	gold quality
lower esophagus mucosa	UBERON:0035834	84.25	gold quality
mononuclear cell	CL:0000842	84.21	gold quality
adrenal gland	UBERON:0002369	84.19	gold quality
renal medulla	UBERON:0000362	84.08	gold quality
leukocyte	CL:0000738	83.97	gold quality
lower esophagus	UBERON:0013473	83.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.91	gold quality
ventral tegmental area	UBERON:0002691	83.81	gold quality
pericardium	UBERON:0002407	83.78	gold quality
aorta	UBERON:0000947	83.66	gold quality
adult mammalian kidney	UBERON:0000082	83.64	gold quality
vagina	UBERON:0000996	83.60	gold quality
gluteal muscle	UBERON:0002000	83.60	silver quality
smooth muscle tissue	UBERON:0001135	83.50	gold quality
pancreas	UBERON:0001264	83.45	gold quality
superior vestibular nucleus	UBERON:0007227	83.39	gold quality
lower lobe of lung	UBERON:0008949	83.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.33	gold quality
colonic epithelium	UBERON:0000397	83.31	gold quality
gastrocnemius	UBERON:0001388	83.15	gold quality
right uterine tube	UBERON:0001302	83.11	gold quality
right testis	UBERON:0004534	83.11	gold quality
endocervix	UBERON:0000458	83.04	gold quality
medulla oblongata	UBERON:0001896	83.04	gold quality
esophagus	UBERON:0001043	82.96	gold quality
body of uterus	UBERON:0009853	82.96	gold quality
vena cava	UBERON:0004087	82.95	gold quality
palpebral conjunctiva	UBERON:0001812	82.94	gold quality
lateral globus pallidus	UBERON:0002476	82.87	gold quality
muscle of leg	UBERON:0001383	82.79	gold quality
bronchial epithelial cell	CL:0002328	82.76	gold quality
pigmented layer of retina	UBERON:0001782	82.71	gold quality
left coronary artery	UBERON:0001626	82.68	gold quality
coronary artery	UBERON:0001621	82.64	gold quality
right coronary artery	UBERON:0001625	82.62	gold quality
left ovary	UBERON:0002119	82.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.59	silver quality
cardia of stomach	UBERON:0001162	82.56	gold quality
ascending aorta	UBERON:0001496	82.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.56	gold quality
thoracic aorta	UBERON:0001515	82.53	gold quality
pylorus	UBERON:0001166	82.51	gold quality
descending thoracic aorta	UBERON:0002345	82.51	gold quality
pituitary gland	UBERON:0000007	82.50	gold quality
tendon of biceps brachii	UBERON:0008188	82.50	silver quality
seminal vesicle	UBERON:0000998	82.49	gold quality
lymph node	UBERON:0000029	82.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.48	gold quality
adenohypophysis	UBERON:0002196	82.43	gold quality
fundus of stomach	UBERON:0001160	82.34	gold quality
dorsal plus ventral thalamus	UBERON:0001897	82.27	gold quality
blood	UBERON:0000178	82.20	gold quality
metanephros cortex	UBERON:0010533	82.20	gold quality
prostate gland	UBERON:0002367	82.19	gold quality
right lobe of thyroid gland	UBERON:0001119	82.14	gold quality
substantia nigra pars compacta	UBERON:0001965	82.14	gold quality
ovary	UBERON:0000992	82.12	gold quality
esophagus mucosa	UBERON:0002469	82.10	gold quality
body of pancreas	UBERON:0001150	82.09	gold quality
minor salivary gland	UBERON:0001830	82.09	gold quality
mucosa of transverse colon	UBERON:0004991	82.09	gold quality
ectocervix	UBERON:0012249	82.07	gold quality
left lobe of thyroid gland	UBERON:0001120	82.02	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.00	gold quality
thyroid gland	UBERON:0002046	81.99	gold quality
muscle organ	UBERON:0001630	81.97	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	31.3
Locus coeruleus	tissue	21.1
Corpus callosum	tissue	17.6
Hippocampus	tissue	16.4	not detected
Nucleus accumbens	tissue	16.1
Caudate putamen	tissue	15.6
Postcentral gyrus	tissue	15.2
Parathyroid gland	tissue	13.2	medium
Medulla oblongata	tissue	13.2
Substantia nigra	tissue	13.2
Frontal cortex	tissue	12.9
Midbrain	tissue	12.9
Thalamus	tissue	12.5
Spinal cord	tissue	12.5
Superior colliculi	tissue	12.3
Periaqueductal gray	tissue	12.3
Putamen	tissue	12.0
Pons	tissue	11.9
Ventral forebrain	tissue	11.5
Hypothalamus	tissue	11.4
Septum	tissue	10.8
Cerebral cortex	tissue	10.6	medium
Kidney	tissue	10.6	medium
Somatosensory cortex	tissue	10.6
Occipital cortex	tissue	10.2
Hippocampal formation	tissue	9.9
Basal ganglia	tissue	9.4	not detected
Thyroid gland	tissue	9.3	low
Cerebellum	tissue	9.2	not detected
Olfactory bulb	tissue	9.2
Insular cortex	tissue	9.2
Testis	tissue	9.0	medium
Amygdala	tissue	9.0
Retrosplenial cortex	tissue	8.9
Motor cortex	tissue	8.8
Smooth muscle	tissue	8.7	not detected
Prefrontal cortex	tissue	8.6
Temporal cortex	tissue	8.6
Adipose tissue	tissue	8.5	medium
Retrosplenial and cingulate cortex	tissue	8.5
Retina	tissue	8.4
Entorhinal cortex	tissue	8.4
Seminal vesicle	tissue	8.1	medium
Tonsil	tissue	8.1	medium
Thymus	tissue	7.8
Liver	tissue	7.7	not detected
Urinary bladder	tissue	7.6	low
Fallopian tube	tissue	7.5	medium
Adrenal gland	tissue	7.3	medium
Esophagus	tissue	7.2	medium
Prostate	tissue	7.2	not detected
Heart muscle	tissue	7.1	low
Lung	tissue	7.0	medium
Lymph node	tissue	6.6	not detected
Endometrium 1	tissue	6.6	medium
Cervix	tissue	6.5	medium
Tongue	tissue	6.5
Stomach 1	tissue	6.3	medium
Appendix	tissue	6.3	low
Rectum	tissue	6.2	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Globus pallidus, externus (29.9), Red nucleus (29.6), Globus pallidus, internus (28.3), Lateral vestibular nucleus (27.8), Inferior olive (27.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CEP104 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 97 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.47e-17, LOEUF 0.851, missense Z 1.51 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000378230 — one region, missense o/e 0.91.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2687282) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1
preweaning lethality, incomplete penetrance	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CCDC27	protein-coding	148870
DFFB	protein-coding	1677
SMIM1	protein-coding	388588
LRRC47	protein-coding	57470
LINC01134	ncRNA	100133612
C1orf174	protein-coding	339448
TP73	protein-coding	7161
LINC01345	ncRNA	105376672
LINC01346	ncRNA	728716
LINC02780	ncRNA	105376673

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
IPR059245	CEP104_TOG	Domain

Pfam: PF21038, PF21039, PF21040

UniProt features (59 total): helix 29, 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 by resolution:

PDB	Title	Method	Resolution (Å)
5LPI	Structure of the zinc finger array of Cep104	X-RAY DIFFRACTION	1.8
5LPH	Structure of the TOG domain of human Cep104	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system, Mental and behavioural disorders

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): spindle pole (GO:0000922), centrosome (GO:0005813), centriole (GO:0005814), cilium (GO:0005929)

GO top-level categories

10 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 6 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
centriole	CC	direct assay
cilium	CC	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 718 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP104	CEP97	Q8IW35	738
CEP104	CEP290	O15078	659
CEP104	KATNIP	O60303	633
CEP104	TOGARAM1	Q9Y4F4	616
CEP104	CCP110	O43303	604
CEP104	CSPP1	Q1MSJ5	596
CEP104	CEP164	Q9UPV0	592
CEP104	ARL13B	Q3SXY8	592
CEP104	ARMC9	Q7Z3E5	585
CEP104	CEP89	Q96ST8	573
CEP104	CEP83	Q9Y592	543
CEP104	KIF24	Q5T7B8	539
CEP104	CFAP97D1	B2RV13	536
CEP104	CEP78	Q5JTW2	525
CEP104	TTBK2	Q6IQ55	516

IntAct

Human interaction partners of CEP104 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
CCDC66	proximity	0.540	3
CSPP1	physical association	0.540	2
TOGARAM1	physical association	0.540	2
ARMC9	physical association	0.400	2
PPP1R13B	physical association	0.400	1
RRBP1	physical association	0.400	1
VSIG8	physical association	0.400	1
SF1	physical association	0.000	4
NR2F6	physical association	0.000	1

BioGRID (96 interactions; top human partners by supporting records): CAMSAP2 (Proximity Label-MS; 2 records), CEP162 (Proximity Label-MS; 2 records), CEP290 (Proximity Label-MS; 2 records), CEP97 (Proximity Label-MS; 2 records), ADSL (Proximity Label-MS), AHCY (Proximity Label-MS), ALMS1 (Proximity Label-MS), AMBRA1 (Proximity Label-MS), AP4E1 (Proximity Label-MS), AP4S1 (Proximity Label-MS), APBB1 (Proximity Label-MS), ARPC3 (Proximity Label-MS), C21orf2 (Proximity Label-MS), CACYBP (Proximity Label-MS), CALM2 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for CEP104: 719 ClinVar records (46 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	28
Uncertain significance	208
Likely benign	248
Benign	123

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 46 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1322057	NM_014704.4(CEP104):c.2081_2084del (p.Gln694fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
434718	NM_014704.4(CEP104):c.49del (p.Asp17fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1704568	NM_014704.4(CEP104):c.2286del (p.Glu762fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3583701	NM_014704.4(CEP104):c.2088_2091del (p.Glu697fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
221274	NM_014704.4(CEP104):c.735+2T>C	Pathogenic	criteria provided, single submitter	2
1700581	NM_014704.4(CEP104):c.643C>T (p.Arg215Ter)	Pathogenic	criteria provided, single submitter	2
542193	NM_014704.4(CEP104):c.1082_1091del (p.Pro361fs)	Pathogenic	criteria provided, single submitter	1
2691290	NM_014704.4(CEP104):c.1232del (p.Gly411fs)	Pathogenic	criteria provided, single submitter	1
3004548	NM_014704.4(CEP104):c.1745del (p.His582fs)	Pathogenic	criteria provided, single submitter	1
3360460	NM_014704.4(CEP104):c.48del (p.Asp17fs)	Pathogenic	criteria provided, single submitter	1
3646990	NM_014704.4(CEP104):c.157A>T (p.Arg53Ter)	Pathogenic	criteria provided, single submitter	1
4526232	NM_014704.4(CEP104):c.2080_2083del (p.Gln694fs)	Pathogenic	criteria provided, single submitter	1
4700540	NM_014704.4(CEP104):c.1351C>T (p.Arg451Ter)	Pathogenic	criteria provided, single submitter	1
221276	NM_014704.4(CEP104):c.496C>T (p.Arg166Ter)	Likely pathogenic	criteria provided, single submitter	2
1677239	NM_014704.4(CEP104):c.1867_1870del (p.Tyr623fs)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CEP104’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 2,069):

Position(s)	Effect	Δscore	Sites
1:3816278–3816279	donor_loss	1.0000	5
1:3816371–3816372	acceptor_loss	1.0000	4
1:3816378	acceptor_gain	1.0000
1:3825293	donor_gain	1.0000
1:3826373	donor_gain	1.0000
1:3829257	donor_gain	1.0000
1:3829264–3829266	donor_loss	1.0000	6
1:3829374–3829375	acceptor_loss	1.0000	2
1:3831044–3831045	donor_loss	1.0000	3
1:3831170	acceptor_gain	1.0000

AlphaMissense

1,502 missense substitutions predicted likely pathogenic (of 6,076 scored), across 413 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M204	9	0.868	0.988
H798	8	0.991	0.998
H772	8	0.988	0.997
F756	8	0.984	0.999
H862	8	0.977	0.993
D199	8	0.970	0.987
F202	8	0.955	0.996
D770	8	0.950	0.981
F764	8	0.929	0.989
N138	8	0.915	0.995
F7	8	0.912	0.992
D207	8	0.909	0.973
D491	8	0.909	0.970
H64	8	0.906	0.969
D198	8	0.899	0.953
N872	8	0.897	0.991
H827	8	0.896	0.971
H27	8	0.889	0.976
D203	8	0.808	0.927
M276	8	0.701	0.827

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.91e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000634
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000786

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
Joubert syndrome 25	Definitive	Autosomal recessive	3
Joubert syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (14 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

14 panels:

Panel	Rating
Cystic renal disease	green
DDG2P	green
Fetal anomalies	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Neurological ciliopathies	green
Ophthalmological ciliopathies	green
Paediatric disorders	green
Rare multisystem ciliopathy Super panel	green
Rare multisystem ciliopathy disorders	green
Renal ciliopathies	green
Unexplained young onset end-stage renal disease	green

Mondo (7): 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), cerebellar ataxia (MONDO:0000437), dystonic disorder (MONDO:0003441), Joubert syndrome (MONDO:0018772)

Orphanet (4): Isolated Joubert syndrome (Orphanet:475), Joubert syndrome and related disorders (Orphanet:140874), Rare ataxia (Orphanet:102002), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

49 phenotypes (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
HP:0002084	Encephalocele
HP:0002104	Apnea
HP:0002126	Polymicrogyria
HP:0002251	Aganglionic megacolon
HP:0002269	Abnormality of neuronal migration
HP:0002317	Unsteady gait
HP:0002346	Head tremor
HP:0002419	Molar tooth sign on MRI
HP:0002553	Highly arched eyebrow
HP:0002650	Scoliosis
HP:0002793	Abnormal pattern of respiration
HP:0002876	Episodic tachypnea
HP:0003312	Abnormal vertebral body morphology
HP:0003593	Infantile onset
HP:0004422	Biparietal narrowing
HP:0007370	Aplasia/Hypoplasia of the corpus callosum
HP:0008872	Feeding difficulties in infancy
HP:0012169	Self-biting
HP:0030680	Abnormal cardiovascular system morphology

GWAS associations

3 associations:

Study	Trait	p-value
GCST004602_27	Mean corpuscular volume	1e-13
GCST002041_1	Blood trace element (Cu levels)	5e-10
GCST008398_7	Glycated hemoglobin levels	6e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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

MeSH disease descriptors

2 disease descriptors:

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 (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation, affects expression	4
Benzo(a)pyrene	affects methylation	2
Particulate Matter	affects expression, increases abundance, increases 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	increases abundance, affects expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 303 trials:

NCT	Phase	Status	Title
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	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	Phase 3	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	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	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	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	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	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
NCT07257939	Phase 3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder
NCT07655115	Phase 3	RECRUITING	Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th
NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00614198	Phase 2	COMPLETED	ScanBrit Dietary Intervention in Autism
NCT00619190	Phase 2	COMPLETED	Study of Aripiprazole to Treat Children and Adolescents With Autism
NCT00709202	Phase 2	COMPLETED	Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
NCT00846547	Phase 2	COMPLETED	Open-Label Study of the Safety and Tolerability of STX209 in Subjects With Autism Spectrum Disorders
NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
NCT01170325	Phase 2	WITHDRAWN	A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG
NCT01205282	Phase 2	COMPLETED	Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
NCT01248130	Phase 2	TERMINATED	Omega-3 Fatty Acids Monotherapy in Children and Adolescents With Autism Spectrum Disorders
NCT01248728	Phase 2	COMPLETED	Omega-3 Fatty Acids For Treatment Of Young Children With Autism (OMG)
NCT01256060	Phase 2	COMPLETED	Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
NCT01288716	Phase 2	COMPLETED	Study of Arbaclofen for the Treatment of Social Withdrawal in Subjects With Autism Spectrum Disorders
NCT01300923	Phase 2	COMPLETED	Acamprosate in Youth With Fragile X Syndrome
NCT01366859	Phase 2	COMPLETED	Nutritional Intervention in Children With Autism Using Whey Protein (Immunocal): Impact on Core Areas of Behavior
NCT01372449	Phase 2	COMPLETED	A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)
NCT01395953	Phase 2	WITHDRAWN	Double-blind Trial of Buspirone for the Treatment of Anxiety in Youth With Autism Spectrum Disorders