CEP250

Summary

CEP250 (centrosomal protein 250, HGNC:1859) is a protein-coding gene on chromosome 20q11.22, encoding Centrosome-associated protein CEP250 (Q9BV73). Plays an important role in centrosome cohesion during interphase.

This gene encodes a core centrosomal protein required for centriole-centriole cohesion during interphase of the cell cycle. The encoded protein dissociates from the centrosomes when parental centrioles separate at the beginning of mitosis. The protein associates with and is phosphorylated by NIMA-related kinase 2, which is also associated with the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 11190 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cone-rod dystrophy and hearing loss 2 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 1,690 total — 81 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_007186

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1859
Approved symbol	CEP250
Name	centrosomal protein 250
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	C-NAP1
Ensembl gene	ENSG00000126001
Ensembl biotype	protein_coding
OMIM	609689
Entrez	11190

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 13 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000397524, ENST00000397527, ENST00000420564, ENST00000422671, ENST00000425096, ENST00000425525, ENST00000425934, ENST00000446710, ENST00000461386, ENST00000465987, ENST00000474829, ENST00000476146, ENST00000487467, ENST00000621352, ENST00000706827, ENST00000706828, ENST00000706829, ENST00000706830, ENST00000706831, ENST00000706832, ENST00000853588, ENST00000937927

RefSeq mRNA: 2 — MANE Select: NM_007186 NM_001318219, NM_007186

CCDS: CCDS13255

Canonical transcript exons

ENST00000397527 — 35 exons

Exon	Start	End
ENSE00000860228	35475502	35475646
ENSE00000860230	35477871	35478101
ENSE00000860231	35479231	35479424
ENSE00001049017	35459983	35460105
ENSE00001273878	35458304	35458374
ENSE00001607714	35465743	35465825
ENSE00001649421	35473870	35474052
ENSE00001649545	35467304	35467555
ENSE00001657482	35473374	35473552
ENSE00001668938	35472673	35472831
ENSE00001695610	35463575	35463631
ENSE00002205636	35462265	35462553
ENSE00003495909	35472050	35472151
ENSE00003541125	35466966	35467072
ENSE00003569818	35476449	35476595
ENSE00003790098	35466039	35466204
ENSE00003997089	35508943	35509044
ENSE00003997090	35500049	35500169
ENSE00003997091	35502390	35505005
ENSE00003997093	35508035	35508190
ENSE00003997094	35509998	35510054
ENSE00003997095	35501845	35501966
ENSE00003997096	35511363	35519280
ENSE00003997097	35497719	35498067
ENSE00003997099	35494524	35494657
ENSE00003997100	35496577	35496715
ENSE00003997102	35490637	35490804
ENSE00003997104	35479646	35479773
ENSE00003997105	35507738	35507851
ENSE00003997107	35493429	35493572
ENSE00003997108	35455598	35455751
ENSE00003997109	35479976	35480145
ENSE00003997110	35491212	35491346
ENSE00003997113	35498595	35498716
ENSE00003997114	35469890	35469986

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 95.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3878 / max 100.4753, expressed in 1760 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184300	10.1133	1753
184301	1.1865	681
184302	0.0879	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.49	gold quality
ventricular zone	UBERON:0003053	93.65	gold quality
cortical plate	UBERON:0005343	92.32	gold quality
granulocyte	CL:0000094	92.20	gold quality
ganglionic eminence	UBERON:0004023	91.01	gold quality
diaphragm	UBERON:0001103	90.85	gold quality
stromal cell of endometrium	CL:0002255	90.07	gold quality
cerebellar hemisphere	UBERON:0002245	89.31	gold quality
cerebellar cortex	UBERON:0002129	89.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.90	gold quality
calcaneal tendon	UBERON:0003701	88.74	gold quality
lymph node	UBERON:0000029	88.16	gold quality
colonic epithelium	UBERON:0000397	87.53	gold quality
spleen	UBERON:0002106	87.52	gold quality
cerebellum	UBERON:0002037	87.43	gold quality
right uterine tube	UBERON:0001302	86.89	gold quality
left testis	UBERON:0004533	85.64	gold quality
skin of leg	UBERON:0001511	85.43	gold quality
right testis	UBERON:0004534	85.37	gold quality
skin of abdomen	UBERON:0001416	85.30	gold quality
prefrontal cortex	UBERON:0000451	85.26	gold quality
nucleus accumbens	UBERON:0001882	84.77	gold quality
body of uterus	UBERON:0009853	84.70	gold quality
apex of heart	UBERON:0002098	84.64	gold quality
sperm	CL:0000019	84.43	silver quality
right ovary	UBERON:0002118	84.42	gold quality
muscle of leg	UBERON:0001383	84.29	gold quality
hypothalamus	UBERON:0001898	84.21	gold quality
rectum	UBERON:0001052	84.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	6.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting CEP250, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-649	97.96	67.21	704
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-10A-3P	93.57	64.43	451

Literature-anchored findings (GeneRIF, showing 14)

• Data show that the dissociation of C-Nap1 from mitotic centrosomes is regulated by localized phosphorylation rather than generalized proteolysis. (PMID:12140259)
• CEP135 acts as a platform protein for C-NAP1 at the centriole. (PMID:18851962)
• C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis. (PMID:23070519)
• Centlein complexes with C-Nap1 and Cep68 at the proximal ends of centrioles during interphase. (PMID:24554434)
• multisite phosphorylation precipitates centrosome disjunction at the onset of mitosis (PMID:24695856)
• A homozygous nonsense CEP250 mutation, in combination with a heterozygous C2orf71 nonsense mutation, causes an atypical form of Usher syndrome, characterised by early-onset sensorineural hearing loss and a relatively mild retinitis pigmentosa. (PMID:24780881)
• ASPP1/2 interacted with centrosome linker protein C-Nap1. Co-depletion of ASPP1 and ASPP2 inhibited re-association of C-Nap1 with centrosome at the end of mitosis. (PMID:25660448)
• C-NAP1-null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with reexpression of C-NAP1 rescuing both phenotypes. Centrosome amplification induced by DNA damage or by PLK4 or CDK2 overexpression was markedly reduced in the absence of C-NAP1. (PMID:28100636)
• Our data indicate that mutations of CEP250 can cause mild cone-rod dystrophy (CRD) and early-onset sensorineural hearing loss (SNHL) in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease. (PMID:29718797)
• CEP250 mutation is associated with Usher syndrome. (PMID:30459346)
• Study identified a nonsense mutation (c.562C>T, p.R188*) in CEP250 in a consanguineous family with nonsyndromic retinitis pigmentosa (RP). The disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations a novel Cep250 knockin mouse line. (PMID:30998843)
• Involvement of NEK2 and its interaction with NDC80 and CEP250 in hepatocellular carcinoma. (PMID:33109182)
• Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome. (PMID:34223797)
• Circ_0060077 Knockdown Alleviates High-Glucose-Induced Cell Apoptosis, Oxidative Stress, Inflammation and Fibrosis in HK-2 Cells via miR-145-5p/VASN Pathway. (PMID:35729462)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep135	ENSDARG00000002991
danio_rerio	crocc2	ENSDARG00000017425
danio_rerio	si:dkey-230p4.1	ENSDARG00000020834
mus_musculus	Cep250	ENSMUSG00000038241
rattus_norvegicus	Cep250	ENSRNOG00000019340
drosophila_melanogaster	Root	FBGN0039152
caenorhabditis_elegans		WBGENE00022500

Paralogs (4): CROCC (ENSG00000058453), TSGA10 (ENSG00000135951), CEP135 (ENSG00000174799), CROCC2 (ENSG00000226321)

Protein

Protein identifiers

Centrosome-associated protein CEP250 — Q9BV73 (reviewed: Q9BV73)

Alternative names: 250 kDa centrosomal protein, Centrosomal Nek2-associated protein 1, Centrosomal protein 2

All UniProt accessions (14): Q9BV73, A0A087WZ34, A0A9L9PXD2, A0A9L9PXK6, A0A9L9PXX3, A0A9L9PXZ7, A6PVI9, E7ETF9, E9PHT2, H0Y5R2, H7C0D6, H7C0P0, Q5JWS5, Q5JWS6

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in centrosome cohesion during interphase. Recruits CCDC102B to the proximal ends of centrioles. Maintains centrosome cohesion by forming intercentriolar linkages. Accumulates at the proximal end of each centriole, forming supramolecular assemblies with viscous material properties that promote organelle cohesion. May be involved in ciliogenesis.

Subunit / interactions. Monomer and homodimer. Forms a complex in vitro with both NEK2 kinase and the PPP1CC catalytic subunit of protein phosphatase 1 (PP1). Interacts with CEP135. Interacts with CROCC/rootletin. Interacts with CNTLN. Interacts with NIN (via C-terminus). Interacts with CCDC102B (via N-terminus); the interaction results in recruitment of CCDC102B to the proximal ends of centrioles.

Subcellular location. Cytoplasm. Perinuclear region. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cilium basal body. Cell projection. Cilium. Photoreceptor outer segment. Photoreceptor inner segment.

Tissue specificity. Ubiquitously and weakly expressed.

Post-translational modifications. Differentially phosphorylated during cell cycle. Phosphorylation may regulate association/dissociation from centrosome. During M phase of mitosis, C-terminal part is phosphorylated by NEK2, suggesting that it may trigger the dissociation from the mitotic centrosome. Dephosphorylated in vitro by the PP1 phosphatase.

Disease relevance. Cone-rod dystrophy and hearing loss 2 (CRDHL2) [MIM:618358] An autosomal recessive disease defined by the association of progressive cone-rod dystrophy with sensorineural hearing loss. Cone-rod dystrophy is characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Antibodies against CEP2 are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BV73-1	1	yes
Q9BV73-2	2

RefSeq proteins (2): NP_001305148, NP_009117* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR055167	Rootletin-like_CC	Domain
IPR057658	CEP250_CC	Domain

Pfam: PF15035, PF25774

UniProt features (48 total): sequence conflict 13, sequence variant 9, modified residue 7, region of interest 6, coiled-coil region 5, compositionally biased region 5, chain 1, splice variant 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6OQA	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV73-F1	64.68	0.00

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 (7): 2138, 2218, 2229, 2252, 2322, 2417, 2421

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 175 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_DN, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_CILIUM_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_RESPONSE_TO_RADIATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS

GO Biological Process (11): mitotic cell cycle (GO:0000278), intracellular protein localization (GO:0008104), centriole-centriole cohesion (GO:0010457), regulation of centriole-centriole cohesion (GO:0030997), detection of light stimulus involved in visual perception (GO:0050908), cilium assembly (GO:0060271), protein localization to centrosome (GO:0071539), positive regulation of protein localization to centrosome (GO:1904781), non-motile cilium assembly (GO:1905515), cell projection organization (GO:0030030), protein localization to organelle (GO:0033365)

GO Molecular Function (2): protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (15): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), centrosome (GO:0005813), centriole (GO:0005814), microtubule organizing center (GO:0005815), cytosol (GO:0005829), spindle pole centrosome (GO:0031616), protein-containing complex (GO:0032991), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
microtubule organizing center	3
centrosome cycle	2
intracellular membraneless organelle	2
cytoplasm	2
cell cycle	1
mitotic nuclear division	1
macromolecule localization	1
cell cycle process	1
centriole-centriole cohesion	1
regulation of cell cycle process	1
visual perception	1
detection of light stimulus involved in sensory perception	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to microtubule organizing center	1
protein localization to centrosome	1
positive regulation of protein localization	1
regulation of protein localization to centrosome	1
cilium assembly	1
cellular component organization	1
intracellular protein localization	1
protein binding	1
binding	1
photoreceptor cell cilium	1
centriole	1
microtubule cytoskeleton	1
spindle pole	1
centrosome	1
cellular_component	1
cilium	1
extracellular vesicle	1
intracellular anatomical structure	1
intraciliary transport particle	1

Protein interactions and networks

STRING

2294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP250	NIN	Q8N4C6	901
CEP250	CROCC	Q5TZA2	899
CEP250	NEK2	P51955	894
CEP250	CNTLN	Q9NXG0	882
CEP250	CNTRL	Q7Z7A1	834
CEP250	LRRC45	Q96CN5	809
CEP250	PCNT	O95613	696
CEP250	NEK11	Q8NG66	645
CEP250	CEP78	Q5JTW2	618
CEP250	CEP290	O15078	613
CEP250	PCARE	A6NGG8	608
CEP250	PDZD7	Q9H5P4	604
CEP250	CEP135	Q66GS9	590
CEP250	CLRN1	P58418	583
CEP250	USH1G	Q495M9	580

IntAct

76 interactions, top by confidence:

A	B	Type	Score
LZTFL1	BBS9	psi-mi:“MI:0914”(association)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
SIK2	CEP250	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
SIK2	CEP250	psi-mi:“MI:0915”(physical association)	0.620
CEP250	SIK2	psi-mi:“MI:0915”(physical association)	0.620
CEP250	SIK2	psi-mi:“MI:0403”(colocalization)	0.620
OPTN	CEP250	psi-mi:“MI:0915”(physical association)	0.560
rep	CEP250	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
CENPK	DHRS12	psi-mi:“MI:0914”(association)	0.530
PPP1R13B	CCDC85C	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	YWHAE	psi-mi:“MI:0914”(association)	0.530
COG3	TBCC	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
SGF29	MATN2	psi-mi:“MI:0914”(association)	0.530
Axin2	CEP250	psi-mi:“MI:0915”(physical association)	0.460

BioGRID (337): CEP250 (Affinity Capture-RNA), CEP250 (Affinity Capture-RNA), CEP250 (Affinity Capture-RNA), CEP250 (Affinity Capture-RNA), CEP250 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), CEP250 (Proximity Label-MS), CEP250 (Proximity Label-MS), CEP250 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), CEP250 (Affinity Capture-MS)

ESM2 similar proteins: A0JMK8, A0JNT9, A2AIV8, A6NI79, A9QT41, B2RZ86, B3DLE8, B8JK76, B9V5F5, F1R4Y7, O35550, O35551, O88522, P0CF95, Q08DR9, Q0IHN7, Q0V9T6, Q15276, Q29RS0, Q2MJU7, Q3KR99, Q3SWS9, Q502I3, Q5BIX7, Q5HZK9, Q5U4E6, Q60952, Q6DCD4, Q6DIX6, Q6GLX3, Q6NRW2, Q6P402, Q6PGZ0, Q6TMG5, Q6ZP65, Q6ZU80, Q86SQ7, Q8BI22, Q8BVL9, Q8CHW5

Diamond homologs: O61308, Q09EF7, Q9BV73, H7BZ55, Q5TZA2, Q60952, Q8CJ40, Q8IVE0

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
PCM1	up-regulates	CEP250	relocalization
SIK2	down-regulates	CEP250	phosphorylation
SIK2	unknown	CEP250	phosphorylation
NEK2	down-regulates	CEP250	phosphorylation
SCYL1	“down-regulates activity”	CEP250	relocalization
CEP250	down-regulates	Centrosome_separation
LRRC45	“up-regulates activity”	CEP250	binding
CEP250	“up-regulates activity”	CCDC102B	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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	6	17.6×	1e-04
Loss of proteins required for interphase microtubule organization from the centrosome	6	17.6×	1e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	17.1×	1e-04
AURKA Activation by TPX2	6	16.9×	1e-04
Regulation of PLK1 Activity at G2/M Transition	7	16.4×	8e-05
Recruitment of mitotic centrosome proteins and complexes	6	15.1×	2e-04
Recruitment of NuMA to mitotic centrosomes	6	12.9×	3e-04
Anchoring of the basal body to the plasma membrane	6	12.6×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	5	48.2×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

1690 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	81
Likely pathogenic	15
Uncertain significance	826
Likely benign	635
Benign	65

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068511	NM_007186.6(CEP250):c.2383C>T (p.Gln795Ter)	Pathogenic
1071914	NM_007186.6(CEP250):c.5959C>T (p.Gln1987Ter)	Pathogenic
1075845	NM_007186.6(CEP250):c.2388dup (p.Val797fs)	Pathogenic
1359477	NM_007186.6(CEP250):c.337del (p.Ser112_Leu113insTer)	Pathogenic
1360232	NM_007186.6(CEP250):c.5725C>T (p.Gln1909Ter)	Pathogenic
1376746	NM_007186.6(CEP250):c.94dup (p.Ala32fs)	Pathogenic
1391338	NM_007186.6(CEP250):c.1235del (p.Cys412fs)	Pathogenic
1395208	NM_007186.6(CEP250):c.5500del (p.Glu1834fs)	Pathogenic
1408071	NM_007186.6(CEP250):c.2986del (p.Glu996fs)	Pathogenic
1408427	NM_007186.6(CEP250):c.6160C>T (p.Gln2054Ter)	Pathogenic
1441102	NM_007186.6(CEP250):c.4027C>T (p.Arg1343Ter)	Pathogenic
1444081	NM_007186.6(CEP250):c.6826C>T (p.Gln2276Ter)	Pathogenic
1451443	NM_007186.6(CEP250):c.263G>A (p.Trp88Ter)	Pathogenic
1452027	NM_007186.6(CEP250):c.6487_6488del (p.Glu2163fs)	Pathogenic
1452407	NM_007186.6(CEP250):c.1468C>T (p.Arg490Ter)	Pathogenic
1453068	NM_007186.6(CEP250):c.3799C>T (p.Gln1267Ter)	Pathogenic
1455407	NC_000020.10:g.(?34050193)(34099455_?)del	Pathogenic
1458267	NM_007186.6(CEP250):c.2848C>T (p.Arg950Ter)	Pathogenic
1459241	NM_007186.6(CEP250):c.2155C>T (p.Arg719Ter)	Pathogenic
1901883	NM_007186.6(CEP250):c.2512del (p.Gln838fs)	Pathogenic
1925483	NM_007186.6(CEP250):c.2206C>T (p.Arg736Ter)	Pathogenic
1926062	NM_007186.6(CEP250):c.6094C>T (p.Arg2032Ter)	Pathogenic
1937734	NM_007186.6(CEP250):c.199C>T (p.Arg67Ter)	Pathogenic
1949785	NM_007186.6(CEP250):c.434G>A (p.Trp145Ter)	Pathogenic
1950385	NM_007186.6(CEP250):c.4495C>T (p.Arg1499Ter)	Pathogenic
1951060	NM_007186.6(CEP250):c.6625C>T (p.Gln2209Ter)	Pathogenic
1951434	NM_007186.6(CEP250):c.6829C>T (p.Gln2277Ter)	Pathogenic
2010972	NM_007186.6(CEP250):c.5969T>A (p.Leu1990Ter)	Pathogenic
2033352	NM_007186.6(CEP250):c.829G>T (p.Glu277Ter)	Pathogenic
2033369	NM_007186.6(CEP250):c.4876C>T (p.Gln1626Ter)	Pathogenic

SpliceAI

5668 predictions. Top by Δscore:

Variant	Effect	Δscore
20:35463629:GGA:G	donor_gain	1.0000
20:35463630:GA:G	donor_gain	1.0000
20:35463630:GAG:G	donor_gain	1.0000
20:35463632:G:GG	donor_gain	1.0000
20:35463636:G:GG	donor_gain	1.0000
20:35463641:GC:G	donor_gain	1.0000
20:35466201:GGAG:G	donor_gain	1.0000
20:35466202:GAGG:G	donor_gain	1.0000
20:35466964:A:AG	acceptor_gain	1.0000
20:35466965:G:GG	acceptor_gain	1.0000
20:35469885:TTTA:T	acceptor_loss	1.0000
20:35469886:TTA:T	acceptor_loss	1.0000
20:35469887:TAGG:T	acceptor_loss	1.0000
20:35469888:AG:A	acceptor_gain	1.0000
20:35469889:G:A	acceptor_gain	1.0000
20:35469889:GGGT:G	acceptor_gain	1.0000
20:35469983:CCTG:C	donor_loss	1.0000
20:35469984:CTG:C	donor_loss	1.0000
20:35469987:G:A	donor_loss	1.0000
20:35470008:A:T	donor_gain	1.0000
20:35472667:TTTCA:T	acceptor_loss	1.0000
20:35472668:TTCA:T	acceptor_loss	1.0000
20:35472669:TCA:T	acceptor_loss	1.0000
20:35472670:CA:C	acceptor_loss	1.0000
20:35472672:GGTC:G	acceptor_gain	1.0000
20:35472828:GCAGG:G	donor_loss	1.0000
20:35472829:CAG:C	donor_loss	1.0000
20:35472830:AG:A	donor_loss	1.0000
20:35472832:GTA:G	donor_loss	1.0000
20:35473370:ACAG:A	acceptor_gain	1.0000

AlphaMissense

15873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:35511469:T:C	L2391P	0.986
20:35462543:T:C	L59P	0.984
20:35467014:T:A	W181R	0.984
20:35467014:T:C	W181R	0.984
20:35467016:G:C	W181C	0.981
20:35467016:G:T	W181C	0.981
20:35511385:T:C	L2363P	0.981
20:35511538:T:C	L2414P	0.981
20:35511448:T:C	L2384P	0.977
20:35511481:T:C	L2395P	0.974
20:35466071:T:C	L120P	0.973
20:35466167:T:C	L152P	0.971
20:35476449:G:C	A573P	0.971
20:35508956:G:C	R2307P	0.971
20:35467036:G:C	R188P	0.969
20:35467003:T:C	L177P	0.968
20:35508171:T:C	L2296P	0.968
20:35511457:T:C	L2387P	0.968
20:35511469:T:A	L2391H	0.968
20:35467039:G:C	R189P	0.965
20:35479755:G:C	A800P	0.964
20:35511477:T:C	S2394P	0.964
20:35511397:G:C	R2367P	0.963
20:35466113:T:C	L134P	0.962
20:35479683:G:C	A776P	0.961
20:35511373:T:C	L2359P	0.961
20:35467309:T:C	L202P	0.959
20:35476576:T:C	L615P	0.958
20:35479675:T:C	L773P	0.957
20:35508150:T:C	L2289P	0.957

dbSNP variants (sampled 300 via entrez): RS1000070130 (20:35509840 G>A), RS1000110351 (20:35479892 G>A), RS1000147117 (20:35505711 G>T), RS1000225122 (20:35489500 G>T), RS1000241006 (20:35496436 T>C), RS1000267575 (20:35472896 G>A,T), RS1000376368 (20:35466314 T>A), RS1000485084 (20:35502867 G>A,C,T), RS1000530391 (20:35499279 CA>C), RS1000547979 (20:35488099 T>A), RS1000598400 (20:35489061 G>A), RS1000642128 (20:35492820 C>G), RS1000657700 (20:35463422 A>G,T), RS1000735068 (20:35469762 C>T), RS1000761822 (20:35470223 T>C)

Disease associations

OMIM: gene MIM:609689 | disease phenotypes: MIM:618358, MIM:276900

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy and hearing loss 2	Definitive	Autosomal recessive
retinitis pigmentosa	Limited	Autosomal recessive
male infertility with azoospermia or oligozoospermia due to single gene mutation	Disputed Evidence	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
cone-rod dystrophy and hearing loss 2	Definitive	AR

Mondo (6): inherited retinal dystrophy (MONDO:0019118), cone-rod dystrophy and hearing loss 2 (MONDO:0020780), optic atrophy (MONDO:0003608), Usher syndrome (MONDO:0019501), retinitis pigmentosa (MONDO:0019200), (MONDO:0018393)

Orphanet (2): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Usher syndrome (Orphanet:886)

HPO phenotypes

4 total (5 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000613	Photophobia
HP:0001757	High-frequency sensorineural hearing impairment
HP:0007663	Reduced visual acuity
HP:0000556	Retinal dystrophy

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000175_30	Height	8.000000e-07
GCST001728_18	Ulcerative colitis	2.000000e-08
GCST002337_170	Amyotrophic lateral sclerosis (sporadic)	1.000000e-07
GCST002702_108	Height	3.000000e-24
GCST005956_31	Waist-to-hip ratio adjusted for BMI	8.000000e-08
GCST005958_16	Waist-to-hip ratio adjusted for BMI (age >50)	6.000000e-06
GCST005962_40	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-08
GCST010002_66	Refractive error	2.000000e-20
GCST010703_112	Brain morphology (MOSTest)	4.000000e-19
GCST012227_1137	Hip circumference adjusted for BMI	7.000000e-10
GCST90090967_29	Height	3.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, decreases expression	1
Smoke	decreases expression	1
Xylitol	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	increases expression	1
Lithium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT02065011	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of SAR421869 in Patients With Usher Syndrome Type 1B
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa