CEP120

Summary

CEP120 (centrosomal protein 120, HGNC:26690) is a protein-coding gene on chromosome 5q23.2, encoding Centrosomal protein of 120 kDa (Q8N960). Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.

This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 153241 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 17
• Clinical variants (ClinVar): 674 total — 21 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 118
• MANE Select transcript: NM_001375405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26690
Approved symbol	CEP120
Name	centrosomal protein 120
Location	5q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36090
Ensembl gene	ENSG00000168944
Ensembl biotype	protein_coding
OMIM	613446
Entrez	153241

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 8 retained_intron, 7 protein_coding, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000306467, ENST00000306481, ENST00000328236, ENST00000503049, ENST00000508138, ENST00000508442, ENST00000513565, ENST00000674620, ENST00000674667, ENST00000674684, ENST00000675003, ENST00000675104, ENST00000675283, ENST00000675330, ENST00000675409, ENST00000675442, ENST00000675444, ENST00000675564, ENST00000675686, ENST00000675814, ENST00000675852, ENST00000676068, ENST00000676384

RefSeq mRNA: 7 — MANE Select: NM_001375405 NM_001166226, NM_001375405, NM_001375406, NM_001375407, NM_001375408, NM_001375409, NM_153223

CCDS: CCDS4134, CCDS54890, CCDS93770, CCDS93771

Canonical transcript exons

ENST00000306467 — 20 exons

Exon	Start	End
ENSE00001382663	123344892	123346753
ENSE00001401128	123422950	123423403
ENSE00001624182	123412399	123412540
ENSE00001656350	123416010	123416124
ENSE00003466871	123418359	123418515
ENSE00003477140	123386518	123386667
ENSE00003486658	123388432	123388606
ENSE00003487435	123391110	123391337
ENSE00003497303	123384951	123385133
ENSE00003510094	123382111	123382200
ENSE00003516180	123389924	123390140
ENSE00003529337	123372650	123372772
ENSE00003567491	123393300	123393497
ENSE00003571605	123349944	123350089
ENSE00003574704	123378336	123378428
ENSE00003578815	123382986	123383082
ENSE00003607471	123382737	123382889
ENSE00003608621	123399136	123399284
ENSE00003630965	123364496	123364594
ENSE00003675920	123377374	123377535

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 94.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9503 / max 132.0634, expressed in 1755 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63154	8.4867	1715
63153	0.9949	543
63152	0.7033	396
63150	0.2116	99
63151	0.2067	90
63156	0.1418	55
63155	0.1138	51
63149	0.0914	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.49	gold quality
epithelial cell of pancreas	CL:0000083	94.47	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.50	gold quality
oviduct epithelium	UBERON:0004804	91.57	gold quality
thymus	UBERON:0002370	91.40	gold quality
germinal epithelium of ovary	UBERON:0001304	91.33	gold quality
adrenal tissue	UBERON:0018303	91.32	gold quality
superficial temporal artery	UBERON:0001614	91.28	gold quality
tendon	UBERON:0000043	91.04	gold quality
layer of synovial tissue	UBERON:0007616	90.05	gold quality
secondary oocyte	CL:0000655	89.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.91	silver quality
oocyte	CL:0000023	88.36	gold quality
epithelium of mammary gland	UBERON:0003244	87.52	gold quality
mammary duct	UBERON:0001765	87.44	gold quality
epithelium of nasopharynx	UBERON:0001951	87.28	gold quality
ovary	UBERON:0000992	86.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.72	gold quality
lymph node	UBERON:0000029	86.69	gold quality
cerebellar vermis	UBERON:0004720	86.59	gold quality
left ovary	UBERON:0002119	86.37	gold quality
tibia	UBERON:0000979	86.28	gold quality
ganglionic eminence	UBERON:0004023	86.24	gold quality
ventricular zone	UBERON:0003053	86.05	gold quality
jejunal mucosa	UBERON:0000399	85.97	gold quality
ileal mucosa	UBERON:0000331	85.93	gold quality
endothelial cell	CL:0000115	85.63	silver quality
caput epididymis	UBERON:0004358	85.60	gold quality
tendon of biceps brachii	UBERON:0008188	85.56	gold quality
fallopian tube	UBERON:0003889	85.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

169 targeting CEP120, 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-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593

Literature-anchored findings (GeneRIF, showing 13)

• Functional characterization of the homologous mouse gene, and comparison to the human protein. (PMID:17920017)
• CEP120 associates with SPICE1 and CPAP, and depletion of any of these proteins results in short procentrioles. Furthermore, CEP120 or CPAP overexpression results in excessive centriole elongation, a process dependent on CEP120, SPICE1, and CPAP. (PMID:23810536)
• CEP120 is a CPAP-interacting protein that positively regulates centriole elongation. (PMID:23857771)
• We establish a novel locus for Jeune asphyxiating thoracic dystrophy on 5q23.2 by linkage analysis and demonstrate that a mutation in CEP120 within this locus is the most likely cause of the disease. (PMID:25361962)
• The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses. (PMID:27208211)
• These results indicate that Cep120 helps to maintain centrosome homeostasis by inhibiting untimely maturation of the daughter centriole, and defines a potentially new molecular defect underlying the pathogenesis of ciliopathies such as Jeune Asphyxiating Thoracic Dystrophy and Joubert syndrome. (PMID:29741480)
• the ciliopathy-associated centriolar protein CEP120 contains three C2 domains. (PMID:29847808)
• CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis. (PMID:30988386)
• Exome sequencing links CEP120 mutation to maternally derived aneuploid conception risk. (PMID:32772081)
• Expression patterns of ciliopathy genes ARL3 and CEP120 reveal roles in multisystem development. (PMID:33297941)
• Update of genetic variants in CEP120 and CC2D2A-With an emphasis on genotype-phenotype correlations, tissue specific transcripts and exploring mutation specific exon skipping therapies. (PMID:33486889)
• CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum. (PMID:34711653)
• RNA sequencing reveals deep intronic CEP120 variant: A report of the diagnostic odyssey for two siblings with Joubert syndrome type 31. (PMID:38050708)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep120	ENSDARG00000091326
mus_musculus	Cep120	ENSMUSG00000048799
rattus_norvegicus	Cep120	ENSRNOG00000017035

Protein

Protein identifiers

Centrosomal protein of 120 kDa — Q8N960 (reviewed: Q8N960)

Alternative names: Coiled-coil domain-containing protein 100

All UniProt accessions (11): Q8N960, A0A6Q8PF64, A0A6Q8PF83, A0A6Q8PFG1, A0A6Q8PG38, A0A6Q8PG66, A0A6Q8PGD1, A0A6Q8PH95, A0A6Q8PHT7, D6R8Z4, D6REX9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner.

Subunit / interactions. Interacts with TACC2, TACC3, CCDC52, TALPID3.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Disease relevance. Short-rib thoracic dysplasia 13 with or without polydactyly (SRTD13) [MIM:616300] A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ’trident’ appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. The disease is caused by variants affecting the gene represented in this entry. Joubert syndrome 31 (JBTS31) [MIM:617761] 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. JBTS31 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the CEP120 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N960-1	1	yes
Q8N960-2	2
Q8N960-3	3

RefSeq proteins (7): NP_001159698, NP_001362334, NP_001362335, NP_001362336, NP_001362337, NP_001362338, NP_694955 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR022136	DUF3668	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR039893	CEP120-like	Family

Pfam: PF00168, PF12416

UniProt features (52 total): strand 19, sequence variant 10, helix 6, sequence conflict 4, splice variant 3, domain 2, region of interest 2, compositionally biased region 2, chain 1, turn 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6FLK	X-RAY DIFFRACTION	1.6
6FLJ	X-RAY DIFFRACTION	1.75
4ICW	X-RAY DIFFRACTION	2.2
4ICX	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N960-F1	79.22	0.51

Functional residue map

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

Post-translational modifications (1): 935

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 480 (showing top): GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, NKX25_02, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_NEUROGENESIS, FOXO4_01, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_PROLIFERATION_IN_FOREBRAIN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_FOREBRAIN_DEVELOPMENT, NKX61_01, GOBP_REGULATION_OF_CENTRIOLE_REPLICATION, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, CEBP_Q2

GO Biological Process (16): centrosome cycle (GO:0007098), positive regulation of centrosome duplication (GO:0010825), cerebral cortex development (GO:0021987), neurogenesis (GO:0022008), interkinetic nuclear migration (GO:0022027), astral microtubule organization (GO:0030953), positive regulation of cilium assembly (GO:0045724), positive regulation of centriole elongation (GO:1903724), positive regulation of establishment of protein localization (GO:1904951), microtubule cytoskeleton organization (GO:0000226), cell population proliferation (GO:0008283), regulation of centrosome duplication (GO:0010824), regulation of protein localization (GO:0032880), regulation of microtubule-based process (GO:0032886), positive regulation of cell cycle process (GO:0090068), positive regulation of organelle assembly (GO:1902117)

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

GO Cellular Component (4): centrosome (GO:0005813), centriole (GO:0005814), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle process	2
centrosome duplication	2
microtubule-based process	2
microtubule organizing center	2
intracellular membraneless organelle	2
microtubule organizing center organization	1
regulation of centrosome duplication	1
positive regulation of cell cycle process	1
pallium development	1
anatomical structure development	1
nervous system development	1
cell differentiation	1
nuclear migration	1
cell proliferation in forebrain	1
spindle organization	1
cytoplasmic microtubule organization	1
cilium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
positive regulation of centriole replication	1
centriole elongation	1
regulation of centriole elongation	1
establishment of protein localization	1
positive regulation of biological process	1
regulation of establishment of protein localization	1
cytoskeleton organization	1
cellular process	1
regulation of centrosome cycle	1
intracellular protein localization	1
regulation of localization	1
regulation of cellular process	1
regulation of cell cycle process	1
positive regulation of cell cycle	1
positive regulation of organelle organization	1
positive regulation of cellular component biogenesis	1
organelle assembly	1
regulation of organelle assembly	1
binding	1
centriole	1

Protein interactions and networks

STRING

1752 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP120	SPICE1	Q8N0Z3	992
CEP120	KIAA0586	Q9BVV6	869
CEP120	CKAP5	Q14008	851
CEP120	PCNT	O95613	847
CEP120	TACC3	Q9Y6A5	842
CEP120	TACC1	O75410	827
CEP120	CNTLN	Q9NXG0	802
CEP120	CPAP	Q9HC77	762
CEP120	CEP290	O15078	735
CEP120	CEP135	Q66GS9	733
CEP120	C2CD3	Q4AC94	732
CEP120	CEP164	Q9UPV0	724
CEP120	POC5	Q8NA72	720
CEP120	CNTROB	Q8N137	713
CEP120	CEP63	Q96MT8	702

IntAct

41 interactions, top by confidence:

A	B	Type	Score
NOL7	WDR43	psi-mi:“MI:0914”(association)	0.640
Cep120	SPICE1	psi-mi:“MI:0915”(physical association)	0.560
CEP120	CEP162	psi-mi:“MI:0915”(physical association)	0.540
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
SPICE1	SERPINB2	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
CEP120	ANK2	psi-mi:“MI:0915”(physical association)	0.470
CEP162	OFD1	psi-mi:“MI:0914”(association)	0.420
CEP162	CCP110	psi-mi:“MI:2364”(proximity)	0.420
HYLS1	CEP120	psi-mi:“MI:0915”(physical association)	0.400
STAT3	CEP120	psi-mi:“MI:0915”(physical association)	0.370
	CEP120	psi-mi:“MI:0915”(physical association)	0.370
CHORDC1	SSR3	psi-mi:“MI:0914”(association)	0.350
MTX2		psi-mi:“MI:0914”(association)	0.350
CEP162	IPO5	psi-mi:“MI:0914”(association)	0.350
	ATP6	psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	SPTBN2	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
POC5	PDHX	psi-mi:“MI:0914”(association)	0.350
PAGE1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
HLX	SCAF4	psi-mi:“MI:0914”(association)	0.350
DONSON	HSP90AA5P	psi-mi:“MI:0914”(association)	0.350
C9orf78	CEP120	psi-mi:“MI:0914”(association)	0.350
TBC1D2B	CEP120	psi-mi:“MI:0914”(association)	0.350
HLX	TLE1	psi-mi:“MI:0914”(association)	0.350
PCM1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
KIAA0753	DVL1	psi-mi:“MI:2364”(proximity)	0.270
ODF2	DDX3X	psi-mi:“MI:2364”(proximity)	0.270
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
LCA5	DVL2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (135): CEP120 (Affinity Capture-MS), CEP120 (Affinity Capture-MS), CEP120 (Proximity Label-MS), CEP120 (Affinity Capture-Western), CEP162 (Affinity Capture-Western), CEP120 (Affinity Capture-MS), CEP120 (Affinity Capture-Western), CEP120 (Proximity Label-MS), CEP120 (Proximity Label-MS), CEP120 (Proximity Label-MS), ALMS1 (Proximity Label-MS), ANAPC1 (Proximity Label-MS), ANK2 (Proximity Label-MS), ARHGAP21 (Proximity Label-MS), CEP131 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: A0JN62, B1H2P5, Q7TSG1, Q8N960

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	7	41.1×	1e-08
Loss of proteins required for interphase microtubule organization from the centrosome	7	41.1×	1e-08
AURKA Activation by TPX2	7	39.5×	1e-08
Recruitment of mitotic centrosome proteins and complexes	7	35.2×	2e-08
Anchoring of the basal body to the plasma membrane	8	33.5×	9e-09
Regulation of PLK1 Activity at G2/M Transition	7	32.9×	3e-08
Recruitment of NuMA to mitotic centrosomes	7	30.2×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	6	104.7×	6e-09
cilium assembly	7	12.3×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	18
Uncertain significance	264
Likely benign	243
Benign	68

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027811	NM_001375405.1(CEP120):c.762del (p.Ser254fs)	Pathogenic
1069907	NM_001375405.1(CEP120):c.1684dup (p.Thr562fs)	Pathogenic
1076569	NM_001375405.1(CEP120):c.2206dup (p.Glu736fs)	Pathogenic
1076850	NM_001375405.1(CEP120):c.1028dup (p.Asp344fs)	Pathogenic
1460221	NC_000005.9:g.(?122682213)(122758692_?)del	Pathogenic
1685613	NM_001375405.1(CEP120):c.1558C>T (p.Gln520Ter)	Pathogenic
1980289	NM_001375405.1(CEP120):c.2164C>T (p.Arg722Ter)	Pathogenic
2060553	NM_001375405.1(CEP120):c.2449C>T (p.Gln817Ter)	Pathogenic
2858930	NM_001375405.1(CEP120):c.2377A>T (p.Lys793Ter)	Pathogenic
3013485	NM_001375405.1(CEP120):c.2743C>T (p.Gln915Ter)	Pathogenic
3670898	NM_001375405.1(CEP120):c.2548C>T (p.Arg850Ter)	Pathogenic
3723419	NM_001375405.1(CEP120):c.1175C>G (p.Ser392Ter)	Pathogenic
446143	NM_001375405.1(CEP120):c.2924T>G (p.Ile975Ser)	Pathogenic
446144	NM_001375405.1(CEP120):c.581T>C (p.Val194Ala)	Pathogenic
446146	NM_001375405.1(CEP120):c.2177T>C (p.Leu726Pro)	Pathogenic
446147	NM_001375405.1(CEP120):c.1138_1139insA (p.Ser380fs)	Pathogenic
4531963	NM_001375405.1(CEP120):c.1789_1792del (p.Ser597fs)	Pathogenic
4535790	NM_001375405.1(CEP120):c.116T>A (p.Leu39Ter)	Pathogenic
4721985	NM_001375405.1(CEP120):c.2026G>T (p.Glu676Ter)	Pathogenic
4735625	NM_001375405.1(CEP120):c.674_675insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTCTTTTACTACTCTTT (p.Leu225delinsPhePhePhePhePhePhePheXaaXaaXaaXaaThrSerTer)	Pathogenic
57490	GRCh38/hg38 5q23.1-23.2(chr5:120695675-124525372)x1	Pathogenic
1324048	NM_001375405.1(CEP120):c.1255+1G>T	Likely pathogenic
1343834	NM_001375405.1(CEP120):c.109_110dup (p.Gln38fs)	Likely pathogenic
1466157	NM_001375405.1(CEP120):c.1039-2A>T	Likely pathogenic
1696573	NM_001375405.1(CEP120):c.50-2113_206+103del	Likely pathogenic
2053431	NM_001375405.1(CEP120):c.1861-2A>G	Likely pathogenic
2142446	NM_001375405.1(CEP120):c.2014-2A>G	Likely pathogenic
2847852	NM_001375405.1(CEP120):c.2580+2T>A	Likely pathogenic
2870301	NM_001375405.1(CEP120):c.1255+1G>A	Likely pathogenic
2904858	NM_001375405.1(CEP120):c.321+1G>A	Likely pathogenic

SpliceAI

3136 predictions. Top by Δscore:

Variant	Effect	Δscore
5:123349939:TATA:T	donor_loss	1.0000
5:123349940:ATACC:A	donor_loss	1.0000
5:123349942:A:C	donor_loss	1.0000
5:123349943:CC:C	donor_loss	1.0000
5:123349962:ATAT:A	donor_gain	1.0000
5:123350085:TCCCT:T	acceptor_gain	1.0000
5:123350086:CCCT:C	acceptor_gain	1.0000
5:123350086:CCCTC:C	acceptor_gain	1.0000
5:123350087:CCTCT:C	acceptor_gain	1.0000
5:123350088:CT:C	acceptor_gain	1.0000
5:123350090:C:CC	acceptor_gain	1.0000
5:123350091:T:C	acceptor_gain	1.0000
5:123350091:T:TC	acceptor_gain	1.0000
5:123364492:ATAC:A	donor_loss	1.0000
5:123364493:TA:T	donor_loss	1.0000
5:123364494:A:AC	donor_gain	1.0000
5:123364495:C:CC	donor_gain	1.0000
5:123364594:CCTAA:C	acceptor_loss	1.0000
5:123364595:C:CA	acceptor_loss	1.0000
5:123364596:T:C	acceptor_loss	1.0000
5:123372773:C:CC	acceptor_gain	1.0000
5:123378331:CATA:C	donor_loss	1.0000
5:123378332:ATACC:A	donor_loss	1.0000
5:123378333:TAC:T	donor_loss	1.0000
5:123378334:A:AC	donor_gain	1.0000
5:123378335:C:CC	donor_gain	1.0000
5:123378335:C:G	donor_loss	1.0000
5:123378335:CCT:C	donor_gain	1.0000
5:123378425:CCAC:C	acceptor_gain	1.0000
5:123378426:CAC:C	acceptor_gain	1.0000

AlphaMissense

6471 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:123382780:A:G	L657P	1.000
5:123418393:A:G	W58R	1.000
5:123418393:A:T	W58R	1.000
5:123364512:A:G	L855P	0.999
5:123364534:A:G	W848R	0.999
5:123364534:A:T	W848R	0.999
5:123364541:C:A	K845N	0.999
5:123364541:C:G	K845N	0.999
5:123382199:A:G	L672P	0.999
5:123382770:C:A	W660C	0.999
5:123382770:C:G	W660C	0.999
5:123382772:A:G	W660R	0.999
5:123382772:A:T	W660R	0.999
5:123391306:C:T	G281E	0.999
5:123391307:C:G	G281R	0.999
5:123391307:C:T	G281R	0.999
5:123391330:A:G	L273P	0.999
5:123393348:G:C	S254R	0.999
5:123393348:G:T	S254R	0.999
5:123393350:T:G	S254R	0.999
5:123416031:T:A	R100S	0.999
5:123416031:T:G	R100S	0.999
5:123416032:C:G	R100T	0.999
5:123416044:A:T	V96D	0.999
5:123416116:C:G	R72P	0.999
5:123416117:G:T	R72S	0.999
5:123416124:C:A	R69S	0.999
5:123416124:C:G	R69S	0.999
5:123418391:C:A	W58C	0.999
5:123418391:C:G	W58C	0.999

dbSNP variants (sampled 300 via entrez): RS1000000864 (5:123373763 A>G,T), RS1000048801 (5:123400403 T>G), RS1000057251 (5:123346313 T>A), RS1000094670 (5:123403344 C>T), RS1000111627 (5:123423525 C>T), RS1000146820 (5:123420788 T>C), RS1000148370 (5:123380062 T>C), RS1000209361 (5:123398062 C>A), RS1000261120 (5:123353935 A>G), RS1000308119 (5:123361035 T>C), RS1000312336 (5:123416955 A>T), RS1000319811 (5:123405267 T>C,G), RS1000334279 (5:123375809 A>T), RS1000359889 (5:123360745 G>A,C), RS1000391930 (5:123405679 G>A)

Disease associations

OMIM: gene MIM:613446 | disease phenotypes: MIM:616300, MIM:617761, MIM:263400

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliopathy	Definitive	Autosomal recessive
short-rib thoracic dysplasia 13 with or without polydactyly	Strong	Autosomal recessive
Joubert syndrome 31	Strong	Autosomal recessive
Joubert syndrome with ocular defect	Supportive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive

Mondo (7): short-rib thoracic dysplasia 13 with or without polydactyly (MONDO:0014577), Joubert syndrome 31 (MONDO:0033310), Chuvash polycythemia (MONDO:0009892), Joubert syndrome with ocular defect (MONDO:0016364), Jeune syndrome (MONDO:0018770), Joubert syndrome (MONDO:0018772), ciliopathy (MONDO:0005308)

Orphanet (2): Jeune syndrome (Orphanet:474), Chuvash erythrocytosis (Orphanet:238557)

HPO phenotypes

118 total (30 of 118 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000062	Ambiguous genitalia
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000090	Nephronophthisis
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000426	Prominent nasal bridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000480	Retinal coloboma
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000572	Visual loss
HP:0000612	Iris coloboma
HP:0000639	Nystagmus

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000442_5	Aortic root size	1.000000e-11
GCST000817_47	Height	2.000000e-10
GCST001524_37	Visceral adipose tissue/subcutaneous adipose tissue ratio	2.000000e-06
GCST002702_53	Height	5.000000e-09
GCST003335_1	Waist circumference	7.000000e-12
GCST003335_5	Waist circumference	4.000000e-06
GCST003335_6	Waist circumference	5.000000e-08
GCST004904_259	Body mass index	5.000000e-09
GCST004904_53	Body mass index	1.000000e-08
GCST005196_87	Coronary artery disease	6.000000e-08
GCST005559_11	Virologic severity in Herpes simplex virus type 2 infection	4.000000e-07
GCST007241_9	Obesity (extreme)	3.000000e-10
GCST007269_237	Pulse pressure	3.000000e-21
GCST008512_14	Multisite chronic pain	2.000000e-08
GCST008839_577	Height	9.000000e-15
GCST010988_340	Adult body size	3.000000e-12
GCST90000025_4	Appendicular lean mass	2.000000e-55

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004340	body mass index
EFO:0009010	HSV2 virologic severity measurement
EFO:0007041	obese body mass index status
EFO:0005763	pulse pressure measurement
EFO:0010100	multisite chronic pain
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563918	Erythrocytosis, Familial, 2 (supp.)
C537571	Jeune syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Valproic Acid	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
manganese chloride	increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	increases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00948376	Not specified	COMPLETED	Natural History of Asphyxiating Thoracic Dystrophy (DTJ)
NCT04143841	Not specified	TERMINATED	Viveye Ocular Magnetic Neurostimulation System (OMNS) for the Management of Severe Dry Eye Disease
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT00068224	Not specified	COMPLETED	Clinical and Molecular Investigations Into Ciliopathies
NCT00495638	Not specified	COMPLETED	Pulmonary Hypertension, Hypoxia and Sickle Cell Disease
NCT01730755	Not specified	NO_LONGER_AVAILABLE	Ruxolitinib for Chuvash Polycythemia