CEP78

Summary

CEP78 (centrosomal protein 78, HGNC:25740) is a protein-coding gene on chromosome 9q21.2, encoding Centrosomal protein of 78 kDa (Q5JTW2). Centriole wall protein that localizes to mature centrioles and regulates centriole and cilia biogenesis.

This gene encodes a centrosomal protein that is both required for the regulation of centrosome-related events during the cell cycle, and required for ciliogenesis. The encoded protein has an N-terminal leucine-rich repeat (LRR) domain with six consecutive LRR repeats, and a C-terminal coiled-coil domain. It interacts with the N-terminal catalytic domain of polo-like kinase 4 (PLK4) and colocalizes with PLK4 to the distal end of the centriole. Naturally occurring mutations in this gene cause defects in primary cilia that result in retinal degeneration and sensorineural hearing loss which are associated with cone-rod degeneration disease as well as Usher syndrome. Low expression of this gene is associated with poor prognosis of colorectal cancer patients.

Source: NCBI Gene 84131 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cone-rod dystrophy and hearing loss (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 667 total — 54 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 22
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001330691

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25740
Approved symbol	CEP78
Name	centrosomal protein 78
Location	9q21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12643
Ensembl gene	ENSG00000148019
Ensembl biotype	protein_coding
OMIM	617110
Entrez	84131

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 19 protein_coding, 4 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000277082, ENST00000376597, ENST00000376598, ENST00000415759, ENST00000424347, ENST00000447629, ENST00000459817, ENST00000476652, ENST00000487108, ENST00000498582, ENST00000536374, ENST00000642214, ENST00000642654, ENST00000642669, ENST00000643273, ENST00000643347, ENST00000643499, ENST00000643847, ENST00000644208, ENST00000645398, ENST00000645865, ENST00000646288, ENST00000647130, ENST00000647199, ENST00000906935, ENST00000906936, ENST00000906937, ENST00000906938, ENST00000962234

RefSeq mRNA: 8 — MANE Select: NM_001330691 NM_001098802, NM_001330691, NM_001330693, NM_001330694, NM_001349838, NM_001349839, NM_001349840, NM_032171

CCDS: CCDS47984, CCDS47985, CCDS83376, CCDS83377, CCDS83378, CCDS87660

Canonical transcript exons

ENST00000643273 — 17 exons

Exon	Start	End
ENSE00000982806	78248762	78248873
ENSE00000982807	78251908	78252043
ENSE00000982808	78253232	78253277
ENSE00000982809	78254836	78254964
ENSE00001471072	78265859	78265906
ENSE00003470561	78248291	78248355
ENSE00003539651	78243462	78243636
ENSE00003542487	78246669	78246782
ENSE00003567927	78264150	78264316
ENSE00003594302	78266442	78266703
ENSE00003605561	78240292	78240364
ENSE00003641544	78262907	78262984
ENSE00003661292	78241696	78241799
ENSE00003662335	78240023	78240195
ENSE00003674694	78265372	78265543
ENSE00003816210	78236075	78236603
ENSE00003903118	78270841	78279690

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4552 / max 163.0101, expressed in 1721 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97020	13.4552	1721

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.02	gold quality
oocyte	CL:0000023	98.67	gold quality
buccal mucosa cell	CL:0002336	94.86	gold quality
ventricular zone	UBERON:0003053	90.29	gold quality
pancreatic ductal cell	CL:0002079	89.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.46	gold quality
ganglionic eminence	UBERON:0004023	87.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.89	gold quality
cortical plate	UBERON:0005343	85.79	gold quality
granulocyte	CL:0000094	85.75	gold quality
right testis	UBERON:0004534	85.40	gold quality
bronchial epithelial cell	CL:0002328	85.23	gold quality
left testis	UBERON:0004533	84.96	gold quality
testis	UBERON:0000473	84.82	gold quality
bronchus	UBERON:0002185	84.21	gold quality
corpus callosum	UBERON:0002336	84.03	gold quality
pigmented layer of retina	UBERON:0001782	83.94	gold quality
retina	UBERON:0000966	83.92	gold quality
smooth muscle tissue	UBERON:0001135	82.70	gold quality
bone marrow	UBERON:0002371	82.52	gold quality
colonic epithelium	UBERON:0000397	82.50	gold quality
thymus	UBERON:0002370	82.21	gold quality
ileal mucosa	UBERON:0000331	81.25	gold quality
body of uterus	UBERON:0009853	81.07	gold quality
calcaneal tendon	UBERON:0003701	80.96	gold quality
rectum	UBERON:0001052	80.89	gold quality
blood	UBERON:0000178	80.79	gold quality
right ovary	UBERON:0002118	80.47	gold quality
left ovary	UBERON:0002119	80.34	gold quality
ovary	UBERON:0000992	80.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.31
E-CURD-114	yes	11.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting CEP78, 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-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-4515	95.70	65.73	716

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• the interaction between Cep78 and the N-terminal catalytic domain of Plk4 is a new and important element in the centrosome overduplication process. (PMID:27246242)
• CEP78 functions as a tumor suppressor in colorectal cancer and low CEP78 expression leads to shorter survival in colorectal cancer patients. (PMID:27357513)
• data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa (PMID:27588451)
• truncating mutations in CEP78 result in a phenotype involving both the visual and auditory systems but different from typical Usher syndrome (PMID:27588452)
• Our results provide evidence that CEP78 is a novel disease-causing gene for Usher syndrome, demonstrating an additional link between ciliopathy and Usher protein network in photoreceptor cells and inner ear hair cells. (PMID:27627988)
• we identify Cep78 as a new player that regulates centrosome homeostasis by inhibiting the final step of the enzymatic reaction catalyzed by EDD-DYRK2-DDB1(Vpr)(BP). (PMID:28242748)
• Low CEP78 expression is associated with differentiated thyroid carcinoma. (PMID:30884127)
• Functional characterization of the first missense variant in CEP78, a founder allele associated with cone-rod dystrophy, hearing loss, and reduced male fertility. (PMID:31999394)
• Centrosome Protein 78 Is Overexpressed in Muscle-Invasive Bladder Cancer and Is Associated with Tumor Molecular Subtypes and Mutation Signatures. (PMID:33119552)
• Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome. (PMID:34223797)
• CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels. (PMID:34259627)
• A novel frameshift variant in CEP78 associated with nonsyndromic retinitis pigmentosa, and a review of CEP78-related phenotypes. (PMID:35240912)
• Loss-of-function mutations in CEP78 cause male infertility in humans and mice. (PMID:36206347)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep78	ENSDARG00000039229
mus_musculus	Cep78	ENSMUSG00000041491
rattus_norvegicus	Cep78	ENSRNOG00000014041
drosophila_melanogaster	CG7886	FBGN0038248

Protein

Protein identifiers

Centrosomal protein of 78 kDa — Q5JTW2 (reviewed: Q5JTW2)

All UniProt accessions (12): Q5JTW2, A0A2R8Y432, A0A2R8Y4C1, A0A2R8Y589, A0A2R8Y5W6, A0A2R8Y7A4, A0A2R8Y7M8, A0A2R8Y7U5, A0A2R8YCP0, A0A2R8YFB0, A0A2U3TZI9, A8MST6

UniProt curated annotations — full annotation on UniProt →

Function. Centriole wall protein that localizes to mature centrioles and regulates centriole and cilia biogenesis. Involved in centrosome duplication: required for efficient PLK4 centrosomal localization and PLK4-induced overduplication of centrioles. Involved in cilium biogenesis and controls cilium length. Acts as a regulator of protein stability by preventing ubiquitination of centrosomal proteins, such as CCP110 and tektins. Associates with the EDVP complex, preventing ubiquitination and degradation of CCP110. Promotes deubiquitination of tektin proteins (TEKT1, TEKT2, TEK3, TEKT4 and TEKT5) via its interaction with USP16.

Subunit / interactions. Interacts with PLK4. Interacts with FAM161A. Interacts with IFT20; regulating IFT20 stability and localization. Interacts with TTC21A; regulating TTC21A stability and localization. Interacts with USP16; promoting USP16-dependent deubiquitination of tektins. Interacts with DCAF1/VPRBP; promoting localization of the EDVP complex to centrosomes. Interacts with CEP350; promoting CEP78 localization to centrosome and centriole.

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

Tissue specificity. Widely expressed. Expressed in different retinal cell types with higher expression in cone compared to rod cells (at protein level).

Disease relevance. Cone-rod dystrophy and hearing loss 1 (CRDHL1) [MIM:617236] 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. Spermatogenic failure. A male infertility disorder characterized by asthenoteratospermia and multiple morphologic abnormalities of the flagella, resulting in reduced sperm motility. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CEP78 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5JTW2-1	1	yes
Q5JTW2-2	2
Q5JTW2-3	3
Q5JTW2-5	4

RefSeq proteins (8): NP_001092272, NP_001317620, NP_001317622, NP_001317623, NP_001336767, NP_001336768, NP_001336769, NP_115547 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR026212	Cep78	Family
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13516

UniProt features (19 total): sequence conflict 4, region of interest 3, splice variant 3, mutagenesis site 2, compositionally biased region 2, modified residue 2, chain 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JTW2-F1	64.28	0.30

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 (2): 325, 327

Mutagenesis-validated functional residues (2):

Position	Phenotype
262	abolished interaction with dcaf1/vprbp.
290	abolished interaction with dcaf1/vprbp.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

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

MSigDB gene sets: 162 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_VESICLE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_CILIUM_MOVEMENT, GOCC_CENTROSOME, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ACROSOME_ASSEMBLY

GO Biological Process (6): flagellated sperm motility (GO:0030317), negative regulation of protein ubiquitination (GO:0031397), cilium organization (GO:0044782), protein localization to cilium (GO:0061512), protein localization to centrosome (GO:0071539), cell projection organization (GO:0030030)

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

GO Cellular Component (8): centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-10 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule organizing center	3
cellular anatomical structure	3
intracellular membraneless organelle	2
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
organelle organization	1
plasma membrane bounded cell projection organization	1
protein localization to organelle	1
protein localization to microtubule organizing center	1
cellular component organization	1
binding	1
centriole	1
cytoplasm	1
cilium	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1143 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP78	CEP250	Q9BV73	618
CEP78	CFAP418	Q96NL8	564
CEP78	ARSG	Q96EG1	530
CEP78	TMEM82	A0PJX8	521
CEP78	TTLL5	Q6EMB2	516
CEP78	TTLL10	Q6ZVT0	488
CEP78	CNTLN	Q9NXG0	484
CEP78	SPATA3	Q8NHX4	482
CEP78	DEUP1	Q05D60	476
CEP78	CEP41	Q9BYV8	474
CEP78	ABHD12	Q8N2K0	474
CEP78	PDZD7	Q9H5P4	464
CEP78	CEP97	Q8IW35	457
CEP78	UBXN11	Q5T124	447
CEP78	CEP290	O15078	442

IntAct

95 interactions, top by confidence:

A	B	Type	Score
RPS14	CCZ1B	psi-mi:“MI:0914”(association)	0.640
Cep78	UBR5	psi-mi:“MI:0915”(physical association)	0.560
CEP78	CEP43	psi-mi:“MI:0914”(association)	0.530
CACNG5	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
EEF2KMT	BCAT2	psi-mi:“MI:0914”(association)	0.530
SYT12	B4GALT5	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF324	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
CEP78	H2BC13	psi-mi:“MI:0915”(physical association)	0.400
CEP78	H2BW1	psi-mi:“MI:0915”(physical association)	0.400
CEP78	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
Cep120	TBC1D31	psi-mi:“MI:0914”(association)	0.350
CEP43	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Ubr5	SFI1	psi-mi:“MI:0914”(association)	0.350
ASPM		psi-mi:“MI:0914”(association)	0.350
SLC16A6	ZNF768	psi-mi:“MI:0914”(association)	0.350
Cep43	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Prkar2a	TBC1D31	psi-mi:“MI:0914”(association)	0.350

BioGRID (135): CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-RNA), CEP78 (Affinity Capture-RNA), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Two-hybrid), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS), CEP78 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IXF6, A1A5R8, A9ZLX4, D3YXJ0, E9PUQ8, G3UZ78, O00750, O15164, O54828, P30052, P40818, P48984, P52963, P59997, P97496, Q02225, Q08AX9, Q08BR4, Q08D35, Q16760, Q1LUC3, Q2I6J1, Q3UWM4, Q498F0, Q5JSH3, Q5JTW2, Q5RHD1, Q60665, Q64398, Q68FF0, Q6INA9, Q6NSI8, Q6NVE8, Q6PDG5, Q6ZMT4, Q7ZVP1, Q80U87, Q86XP1, Q8C5W4, Q8N7X0

Diamond homologs: A2RRS8, Q5JTW2, Q6IRU7, Q9VFH6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	13
Uncertain significance	336
Likely benign	181
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072532	NC_000009.11:g.(?80851267)(80858572_?)del	Pathogenic
1074390	NM_001330691.3(CEP78):c.1419_1422del (p.Glu473_Arg474insTer)	Pathogenic
1074448	NM_001330691.3(CEP78):c.440C>A (p.Ser147Ter)	Pathogenic
1074986	NM_001330691.3(CEP78):c.60del (p.Glu20fs)	Pathogenic
1171013	NM_001330691.3(CEP78):c.1459-1G>T	Pathogenic
1371776	NM_001330691.3(CEP78):c.881del (p.Asn294fs)	Pathogenic
1416146	NM_001330691.3(CEP78):c.1243C>T (p.Gln415Ter)	Pathogenic
1420395	NM_001330691.3(CEP78):c.919_940dup (p.Arg314fs)	Pathogenic
1456180	NM_001330691.3(CEP78):c.1326_1327insACCCATGTGGACCAGGTTGGCCTCGAACTCGTGCCCTCGAACCCTCGCCTCTCTGAGGGTCCGAGGGCCCGCGCAACCGGCCGGAGCCACAATGGCTCCAGGTTGATGATTCTTCA (p.Glu443fs)	Pathogenic
1456588	NM_001330691.3(CEP78):c.341_342insT (p.Cys115fs)	Pathogenic
1456972	NC_000009.11:g.(?79792621)(80944002_?)del	Pathogenic
1457961	NM_001330691.3(CEP78):c.1009C>T (p.Gln337Ter)	Pathogenic
1459637	NM_001330691.3(CEP78):c.1414_1417del (p.Glu472fs)	Pathogenic
1918374	NM_001330691.3(CEP78):c.377dup (p.Leu127fs)	Pathogenic
2083541	NM_001330691.3(CEP78):c.1292dup (p.Ser432fs)	Pathogenic
2132805	NM_001330691.3(CEP78):c.543_556del (p.Val181_Asn182insTer)	Pathogenic
2423690	NC_000009.11:g.(?80854919)(80856735_?)del	Pathogenic
2423691	NC_000009.11:g.(?80851266)(80856548_?)del	Pathogenic
2498281	NM_001330691.3(CEP78):c.1369G>T (p.Glu457Ter)	Pathogenic
2700109	NM_001330691.3(CEP78):c.1649_1653dup (p.Ile552fs)	Pathogenic
2706480	NM_001330691.3(CEP78):c.1327G>T (p.Glu443Ter)	Pathogenic
2709187	NM_001330691.3(CEP78):c.349_352del (p.Ser117fs)	Pathogenic
2737535	NM_001330691.3(CEP78):c.1285_1288dup (p.Pro430fs)	Pathogenic
2751058	NM_001330691.3(CEP78):c.1554del (p.Gly519fs)	Pathogenic
2823042	NM_001330691.3(CEP78):c.711del (p.Asn237fs)	Pathogenic
2975414	NM_001330691.3(CEP78):c.661_665del (p.Pro221fs)	Pathogenic
3011462	NM_001330691.3(CEP78):c.1206-2A>G	Pathogenic
3248945	NM_001330691.3(CEP78):c.40del (p.Asp14fs)	Pathogenic
3249365	NC_000009.12:g.(?78236350)(78243637_78246668)del	Pathogenic
3250203	NM_001330691.3(CEP78):c.1220_1223del (p.Ile407fs)	Pathogenic

SpliceAI

2072 predictions. Top by Δscore:

Variant	Effect	Δscore
9:78240015:T:A	acceptor_gain	1.0000
9:78240021:A:AG	acceptor_gain	1.0000
9:78240021:AG:A	acceptor_gain	1.0000
9:78240022:G:GA	acceptor_gain	1.0000
9:78240022:GG:G	acceptor_gain	1.0000
9:78240022:GGT:G	acceptor_gain	1.0000
9:78240022:GGTT:G	acceptor_gain	1.0000
9:78240022:GGTTC:G	acceptor_gain	1.0000
9:78240193:AAG:A	donor_gain	1.0000
9:78240193:AAGGT:A	donor_loss	1.0000
9:78240194:AG:A	donor_gain	1.0000
9:78240194:AGGT:A	donor_loss	1.0000
9:78240195:GG:G	donor_gain	1.0000
9:78240196:G:GG	donor_gain	1.0000
9:78240196:GTAA:G	donor_loss	1.0000
9:78240288:AAAG:A	acceptor_gain	1.0000
9:78240361:GAAA:G	donor_gain	1.0000
9:78240365:G:GG	donor_gain	1.0000
9:78241694:A:AG	acceptor_gain	1.0000
9:78241695:G:GA	acceptor_gain	1.0000
9:78241695:GT:G	acceptor_gain	1.0000
9:78241695:GTT:G	acceptor_gain	1.0000
9:78241695:GTTA:G	acceptor_gain	1.0000
9:78241795:TAAAG:T	donor_loss	1.0000
9:78241796:AAAGG:A	donor_loss	1.0000
9:78241797:AAGGT:A	donor_loss	1.0000
9:78241798:AGGT:A	donor_loss	1.0000
9:78241800:G:GA	donor_loss	1.0000
9:78241801:T:A	donor_loss	1.0000
9:78243460:A:AG	acceptor_gain	1.0000

AlphaMissense

4619 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:78246678:T:C	L263P	0.998
9:78264282:T:C	F531L	0.998
9:78264284:T:A	F531L	0.998
9:78264284:T:G	F531L	0.998
9:78264301:T:C	L537P	0.998
9:78264304:T:C	L538P	0.998
9:78264273:T:C	F528L	0.997
9:78264275:T:A	F528L	0.997
9:78264275:T:G	F528L	0.997
9:78264291:T:C	F534L	0.997
9:78264293:C:A	F534L	0.997
9:78264293:C:G	F534L	0.997
9:78243550:G:C	R231P	0.996
9:78264304:T:A	L538H	0.996
9:78236513:T:A	W55R	0.995
9:78236513:T:C	W55R	0.995
9:78243494:G:C	W212C	0.995
9:78243494:G:T	W212C	0.995
9:78246672:T:C	L261P	0.995
9:78246772:T:A	N294K	0.995
9:78246772:T:G	N294K	0.995
9:78264283:T:C	F531S	0.995
9:78264292:T:C	F534S	0.995
9:78264312:G:C	A541P	0.995
9:78264274:T:C	F528S	0.994
9:78264288:G:C	A533P	0.994
9:78246756:T:C	L289P	0.993
9:78264295:T:C	L535S	0.993
9:78240323:T:C	L153P	0.992
9:78248768:T:A	W322R	0.992

dbSNP variants (sampled 300 via entrez): RS1000028635 (9:78246438 A>C), RS1000059723 (9:78246115 G>A), RS1000204338 (9:78264659 A>G), RS1000204757 (9:78241207 C>T), RS1000255378 (9:78241024 C>T), RS1000312865 (9:78269288 G>A), RS1000332127 (9:78234345 T>C,G), RS1000371130 (9:78259081 G>A), RS1000509189 (9:78263885 G>C,T), RS1000562740 (9:78250754 A>G), RS1000573612 (9:78256649 C>A,G,T), RS1000793742 (9:78264227 T>C), RS1000806029 (9:78251886 C>A,T), RS1000809522 (9:78263021 G>A), RS1000883378 (9:78236099 G>A,T)

Disease associations

OMIM: gene MIM:617110 | disease phenotypes: MIM:617236, MIM:616038, MIM:268000, MIM:120970

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy and hearing loss	Definitive	Autosomal recessive
cone-rod dystrophy and hearing loss 1	Strong	Autosomal recessive
Usher syndrome type 3	Supportive	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	Strong	AR

Mondo (9): cone-rod dystrophy and hearing loss 1 (MONDO:0020778), cone-rod dystrophy and hearing loss (MONDO:0014980), inherited retinal dystrophy (MONDO:0019118), Neu-Laxova syndrome 2 (MONDO:0014466), retinitis pigmentosa (MONDO:0019200), cone-rod dystrophy (MONDO:0015993), sensorineural hearing loss disorder (MONDO:0020678), optic atrophy (MONDO:0003608), Usher syndrome type 3 (MONDO:0016485)

Orphanet (6): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Neu-Laxova syndrome (Orphanet:2671), Neu-Laxova syndrome due to phosphoserine aminotransferase deficiency (Orphanet:583602), Retinitis pigmentosa (Orphanet:791), Cone rod dystrophy (Orphanet:1872), Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

22 total (23 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000375	Abnormal cochlea morphology
HP:0000407	Sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000572	Visual loss
HP:0000575	Scotoma
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001105	Retinal atrophy
HP:0001751	Abnormal vestibular function
HP:0001756	Vestibular hyporeflexia
HP:0007641	Dyschromatopsia
HP:0007730	Iris hypopigmentation
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0012047	Hemeralopia
HP:0000556	Retinal dystrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
perfluoro-n-nonanoic acid	decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	2
Benzo(a)pyrene	increases methylation, affects methylation	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
propionaldehyde	decreases expression	1
bisphenol A	increases methylation	1
glycidyl methacrylate	decreases expression	1
beta-lapachone	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
celastrol	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
dimethylarsinous acid	decreases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1

Clinical trials (associated diseases)

260 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
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
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
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
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
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
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
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
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)
NCT06592131	PHASE1	NOT_YET_RECRUITING	BF844 Safety and Pharmacokinetic Study in Healthy Volunteers
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration