CEP164

Summary

CEP164 (centrosomal protein 164, HGNC:29182) is a protein-coding gene on chromosome 11q23.3, encoding Centrosomal protein of 164 kDa (Q9UPV0). Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells.

This gene encodes a centrosomal protein involved in microtubule organization, DNA damage response, and chromosome segregation. The encoded protein is required for assembly of primary cilia and localizes to mature centrioles. Defects in this gene are a cause of nephronophthisis-related ciliopathies. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 22897 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CEP164-related ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 1,614 total — 66 pathogenic, 55 likely-pathogenic
• Phenotypes (HPO): 25
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014956

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29182
Approved symbol	CEP164
Name	centrosomal protein 164
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1052, NPHP15
Ensembl gene	ENSG00000110274
Ensembl biotype	protein_coding
OMIM	614848
Entrez	22897

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000278935, ENST00000525416, ENST00000525734, ENST00000527609, ENST00000528706, ENST00000529153, ENST00000532187, ENST00000533153, ENST00000533223, ENST00000533433, ENST00000533570, ENST00000533675, ENST00000533706, ENST00000639320, ENST00000939968, ENST00000939969, ENST00000957770

RefSeq mRNA: 2 — MANE Select: NM_014956 NM_001271933, NM_014956

CCDS: CCDS31683

Canonical transcript exons

ENST00000278935 — 33 exons

Exon	Start	End
ENSE00001130813	117412072	117413266
ENSE00001130821	117338566	117338668
ENSE00001466476	117335605	117335680
ENSE00001466477	117327854	117327904
ENSE00003231581	117351790	117351988
ENSE00003472934	117395123	117395191
ENSE00003476851	117411795	117411917
ENSE00003488503	117361835	117361993
ENSE00003490676	117390777	117390908
ENSE00003492567	117390999	117391215
ENSE00003506855	117344166	117344277
ENSE00003516820	117393004	117393126
ENSE00003524423	117392496	117392627
ENSE00003533847	117392226	117392303
ENSE00003536058	117394920	117395003
ENSE00003542531	117363429	117363506
ENSE00003549139	117371080	117371466
ENSE00003554541	117375708	117375791
ENSE00003588555	117410828	117410894
ENSE00003589614	117396054	117396180
ENSE00003602872	117409618	117409965
ENSE00003616380	117408890	117409028
ENSE00003627379	117397091	117397313
ENSE00003637981	117382796	117382942
ENSE00003646179	117380614	117380705
ENSE00003660748	117396550	117396611
ENSE00003662170	117362404	117362538
ENSE00003670510	117395547	117395722
ENSE00003672627	117373751	117373831
ENSE00003673587	117387203	117387412
ENSE00003673651	117381701	117381868
ENSE00003685417	117407925	117408032
ENSE00003690305	117394350	117394493

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0081 / max 258.3651, expressed in 1795 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116925	5.6770	1686
116924	4.6476	1600
116927	0.5953	157
116929	0.0611	11
116928	0.0271	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.69	gold quality
tendon of biceps brachii	UBERON:0008188	98.12	gold quality
male germ cell	CL:0000015	96.73	gold quality
sural nerve	UBERON:0015488	96.13	gold quality
nipple	UBERON:0002030	95.31	gold quality
right uterine tube	UBERON:0001302	94.96	gold quality
bronchial epithelial cell	CL:0002328	94.94	gold quality
visceral pleura	UBERON:0002401	94.75	gold quality
left testis	UBERON:0004533	94.70	gold quality
parietal pleura	UBERON:0002400	94.69	gold quality
right testis	UBERON:0004534	94.64	gold quality
pleura	UBERON:0000977	93.56	gold quality
pylorus	UBERON:0001166	92.68	gold quality
testis	UBERON:0000473	92.44	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.39	gold quality
medial globus pallidus	UBERON:0002477	92.00	gold quality
body of pancreas	UBERON:0001150	91.78	gold quality
buccal mucosa cell	CL:0002336	91.77	gold quality
saphenous vein	UBERON:0007318	91.77	gold quality
germinal epithelium of ovary	UBERON:0001304	91.69	gold quality
pituitary gland	UBERON:0000007	91.65	gold quality
caput epididymis	UBERON:0004358	91.52	gold quality
tibia	UBERON:0000979	91.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.33	gold quality
gingival epithelium	UBERON:0001949	91.17	gold quality
pericardium	UBERON:0002407	91.08	gold quality
globus pallidus	UBERON:0001875	91.06	gold quality
renal medulla	UBERON:0000362	90.89	gold quality
cerebellar hemisphere	UBERON:0002245	90.87	gold quality
cerebellar cortex	UBERON:0002129	90.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting CEP164, 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-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
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-MIR-4267	99.96	66.53	2368
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 14)

• These data implicate distal appendages in primary cilia formation and identify Cep164 as an excellent marker for these structures. (PMID:17954613)
• Cep164 is a key player in the DNA damage-activated signaling cascade. (PMID:18283122)
• Results show that Cep164 knockdown compromises the cell survival upon UV damage, and that UV irradiation significantly enhances the interaction between Cep164 and XPA. (PMID:19197159)
• Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of hepatocellular carcinoma in Japanese patients with hepatitis C virus. (PMID:22004425)
• Study identifies by whole-exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing Nephronophthisis-related ciliopathies. (PMID:22863007)
• findings indicate that ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional network that is involved in JBTS and NPHP but independent of the ones previously defined by NPHP and MKS proteins (PMID:23150559)
• Cep164 is targeted to the apical domain of the mother centriole to provide the molecular link between the mother centriole and the membrane biogenesis machinery that initiates cilia formation. (PMID:23253480)
• data suggest that TTBK2 also acts upstream of Cep164, contributing to the assembly of distal appendages (PMID:24982133)
• Evidence is provided that TTBK2 effectively phosphorylate Cep164 and Cep97 and inhibits the interaction between Cep164 and its binding partner Dishevelled-3 (an important regulator of ciliogenesis) in a kinase activity-dependent manner. (PMID:25297623)
• This study reveals a novel role for CEP164 in the pathogenesis of nephronophthisis, in which mutations cause ciliary defects coupled with DNA damage induced replicative stress, cell death, and epithelial-to-mesenchymal transition (PMID:25340510)
• data suggest that CEP164 is not required in the DNA damage response. (PMID:26966185)
• these data support a conserved role for CEP164 throughout the development of numerous organs, which, we suggest, accounts for the multi-system disease phenotype of CEP164-mediated Nephronophthisis-related ciliopathies (PMID:31990917)
• Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies. (PMID:34499853)
• Biallelic variants in CEP164 cause a motile ciliopathy-like syndrome. (PMID:36273371)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cep164	ENSMUSG00000043987
rattus_norvegicus	Cep164	ENSRNOG00000029826
drosophila_melanogaster	GCC185	FBGN0037979

Paralogs (3): GOLGA3 (ENSG00000090615), GCC2 (ENSG00000135968), NUMA1 (ENSG00000137497)

Protein

Protein identifiers

Centrosomal protein of 164 kDa — Q9UPV0 (reviewed: Q9UPV0)

All UniProt accessions (6): Q9UPV0, A0A1W2PQ68, E9PI05, E9PIM2, E9PLS8, E9PR73

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1.

Subunit / interactions. Interacts (via N-terminus) with ATRIP. Interacts with ATM, ATR and MDC1. Interacts with XPA (via N-terminus) upon UV irradiation. Interacts with CEP83, CCDC92, TTBK2, DVL3, NPHP3 and weakly with NPHP4. Interacts with DZIP1.

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

Tissue specificity. Expressed in several cell lines.

Post-translational modifications. Phosphorylation at Ser-186 is induced upon DNA-damage caused by treatment with IR irradiation, UV irradiation, hydroxyurea or amphidicolin. Also MDC1-mediated chromatin remodeling is critical for DNA damage-induced phosphorylation.

Disease relevance. Nephronophthisis 15 (NPHP15) [MIM:614845] An autosomal recessive disorder characterized by the association of nephronophthisis with Leber congenital amaurosis and retinal degeneration, often resulting in blindness during childhood. Additional features include seizures, cerebellar vermis hypoplasia, facial dysmorphism, bronchiectasis and liver failure. Nephronophthisis is a chronic tubulo-interstitial nephritis that progresses to end-stage renal failure. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UPV0-1	1	yes
Q9UPV0-2	2

RefSeq proteins (2): NP_001258862, NP_055771* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR036020	WW_dom_sf	Homologous_superfamily
IPR051841	MT-Golgi_org_protein	Family

UniProt features (49 total): compositionally biased region 12, region of interest 6, modified residue 6, sequence variant 5, strand 5, helix 4, turn 4, splice variant 2, chain 1, domain 1, mutagenesis site 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7O06	X-RAY DIFFRACTION	1.6
7O0S	X-RAY DIFFRACTION	1.7
7O3B	X-RAY DIFFRACTION	2.4
7NWJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPV0-F1	63.08	0.30

Antibody-complex structures (SAbDab): 3 — 7O06, 7O0S, 7O3B

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 (6): 186, 201, 566, 1386, 1388, 1443

Mutagenesis-validated functional residues (1):

Position	Phenotype
186	prevents phosphorylation.

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: 210 (showing top): ATACCTC_MIR202, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CILIUM_ORGANIZATION, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOCC_CENTROSOME, GOBP_DNA_DAMAGE_RESPONSE, GOBP_ORGANELLE_ASSEMBLY, LIAO_METASTASIS, CYTAGCAAY_UNKNOWN, WHN_B, ZHANG_BREAST_CANCER_PROGENITORS_UP, SASAKI_ADULT_T_CELL_LEUKEMIA, GOBP_CELL_PROJECTION_ORGANIZATION, CETS1P54_01, GOCC_CENTRIOLE

GO Biological Process (5): DNA repair (GO:0006281), cell division (GO:0051301), cilium assembly (GO:0060271), DNA damage response (GO:0006974), cell projection organization (GO:0030030)

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

GO Cellular Component (11): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), ciliary transition zone (GO:0035869), sperm principal piece (GO:0097228), ciliary transition fiber (GO:0097539), nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

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
cellular anatomical structure	5
microtubule organizing center	2
intracellular membraneless organelle	2
cilium	2
DNA metabolic process	1
DNA damage response	1
cellular process	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
cellular response to stress	1
cellular component organization	1
binding	1
nuclear lumen	1
centriole	1
cytoplasm	1
sperm flagellum	1
intracellular protein-containing complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP164	TTBK2	Q6IQ55	985
CEP164	CEP83	Q9Y592	973
CEP164	SCLT1	Q96NL6	970
CEP164	CEP89	Q96ST8	919
CEP164	FBF1	Q8TES7	895
CEP164	ARL13B	Q3SXY8	824
CEP164	CCP110	O43303	798
CEP164	ATM	Q13315	797
CEP164	RAB3IP	Q96QF0	797
CEP164	C2CD3	Q4AC94	785
CEP164	CEP290	O15078	784
CEP164	NIN	Q8N4C6	774
CEP164	IFT88	Q13099	758
CEP164	CEP97	Q8IW35	750
CEP164	RAB8A	P24407	747

IntAct

79 interactions, top by confidence:

A	B	Type	Score
CEP164	TTBK2	psi-mi:“MI:0914”(association)	0.680
TTBK2	CEP164	psi-mi:“MI:0915”(physical association)	0.680
CEP164	TTBK2	psi-mi:“MI:0915”(physical association)	0.680
SOCS7	NCK2	psi-mi:“MI:0914”(association)	0.670
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
CEP164	CCDC92	psi-mi:“MI:0915”(physical association)	0.600
CCDC92	CEP164	psi-mi:“MI:0915”(physical association)	0.600
CCDC92	CEP164	psi-mi:“MI:0403”(colocalization)	0.600
CLP1	CEP164	psi-mi:“MI:0915”(physical association)	0.560
DVL3	CEP164	psi-mi:“MI:0403”(colocalization)	0.560
CEP164	DVL3	psi-mi:“MI:0915”(physical association)	0.560
DVL3	CEP164	psi-mi:“MI:0915”(physical association)	0.560
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530
SYCE3	RER1	psi-mi:“MI:0914”(association)	0.530
CEP164	SRSF2	psi-mi:“MI:0403”(colocalization)	0.450
CEP164	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
CEP164	HSPA9	psi-mi:“MI:0915”(physical association)	0.400
CEP164	NPHP3	psi-mi:“MI:0915”(physical association)	0.400
NPHP3	CEP164	psi-mi:“MI:0915”(physical association)	0.400
CEP164	MAPK14	psi-mi:“MI:0915”(physical association)	0.370
CEP164	TTBK2	psi-mi:“MI:0915”(physical association)	0.370
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
Ankrd26	TBC1D31	psi-mi:“MI:0914”(association)	0.350

BioGRID (191): CEP164 (Affinity Capture-RNA), CEP164 (Affinity Capture-RNA), CEP164 (Affinity Capture-MS), CEP164 (Proximity Label-MS), CEP164 (Proximity Label-MS), CEP164 (Proximity Label-MS), BTF3 (Proximity Label-MS), C1orf131 (Proximity Label-MS), CAPN1 (Proximity Label-MS), CEBPZ (Proximity Label-MS), CTSB (Proximity Label-MS), DDX24 (Proximity Label-MS), DDX47 (Proximity Label-MS), DNAJB6 (Proximity Label-MS), EBNA1BP2 (Proximity Label-MS)

ESM2 similar proteins: A2AHC3, A2AMT1, A6NCC3, A6NN73, D3Z8E6, D6RF30, E7F5E1, H3BPF8, H3BQL2, H3BSY2, O15061, O35668, P0DX52, P0DX53, P53814, P54256, P54257, P62025, P97434, Q02435, Q06002, Q06637, Q0D2H9, Q0VF96, Q12934, Q3UHU5, Q3V0F0, Q5DU05, Q5T5Y3, Q5TF21, Q60664, Q62627, Q63312, Q6AW69, Q6NZL0, Q6PHN1, Q6WCQ1, Q70IV5, Q80VC9, Q80Y56

Diamond homologs: Q5DU05, Q9UPV0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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	5	13.4×	5e-03
Loss of proteins required for interphase microtubule organization from the centrosome	5	13.4×	5e-03
Anchoring of the basal body to the plasma membrane	7	13.4×	4e-04
AURKA Activation by TPX2	5	12.9×	5e-03
Recruitment of mitotic centrosome proteins and complexes	5	11.5×	6e-03
Regulation of PLK1 Activity at G2/M Transition	5	10.8×	7e-03
Recruitment of NuMA to mitotic centrosomes	5	9.9×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
non-motile cilium assembly	5	17.9×	3e-03
cilium assembly	12	10.9×	6e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

1614 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	66
Likely pathogenic	55
Uncertain significance	736
Likely benign	601
Benign	51

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1009382	NM_014956.5(CEP164):c.1481dup (p.Pro495fs)	Pathogenic
1015384	NM_014956.5(CEP164):c.2656G>T (p.Gly886Ter)	Pathogenic
1179150	NM_014956.5(CEP164):c.1264_1265insTGGCTGG (p.His422fs)	Pathogenic
1371663	NM_014956.5(CEP164):c.3055C>T (p.Gln1019Ter)	Pathogenic
1379611	NM_014956.5(CEP164):c.3109C>T (p.Gln1037Ter)	Pathogenic
1405576	NM_014956.5(CEP164):c.2688_2691del (p.Arg897fs)	Pathogenic
1431411	NM_014956.5(CEP164):c.2942_2943del (p.Glu981fs)	Pathogenic
1454049	NM_014956.5(CEP164):c.1996G>T (p.Glu666Ter)	Pathogenic
1454479	NM_014956.5(CEP164):c.3711_3712del (p.Ser1238fs)	Pathogenic
1454912	NM_014956.5(CEP164):c.1444C>T (p.Gln482Ter)	Pathogenic
1475271	NM_014956.5(CEP164):c.4010dup (p.Asp1337fs)	Pathogenic
1902136	NM_014956.5(CEP164):c.3039_3040dup (p.Gln1014fs)	Pathogenic
1984335	NM_014956.5(CEP164):c.3732G>A (p.Trp1244Ter)	Pathogenic
2015819	NM_014956.5(CEP164):c.241C>T (p.Gln81Ter)	Pathogenic
2016060	NM_014956.5(CEP164):c.381del (p.Ser129fs)	Pathogenic
2040387	NM_014956.5(CEP164):c.40_41del (p.Leu14fs)	Pathogenic
2056914	NM_014956.5(CEP164):c.3685dup (p.Leu1229fs)	Pathogenic
2078300	NM_014956.5(CEP164):c.1819C>T (p.Gln607Ter)	Pathogenic
2078453	NM_014956.5(CEP164):c.2044C>T (p.Gln682Ter)	Pathogenic
2100451	NM_014956.5(CEP164):c.2836G>T (p.Glu946Ter)	Pathogenic
2119268	NM_014956.5(CEP164):c.2998del (p.Ile1000fs)	Pathogenic
2149171	NM_014956.5(CEP164):c.151C>T (p.Arg51Ter)	Pathogenic
2153417	NM_014956.5(CEP164):c.3193del (p.Asp1065fs)	Pathogenic
2707376	NM_014956.5(CEP164):c.3502-2A>G	Pathogenic
2725347	NM_014956.5(CEP164):c.893del (p.Gly298fs)	Pathogenic
2741174	NM_014956.5(CEP164):c.1657C>T (p.Gln553Ter)	Pathogenic
2754654	NM_014956.5(CEP164):c.88_89del (p.Ile29_Leu30insTer)	Pathogenic
2760712	NM_014956.5(CEP164):c.2481del (p.Tyr828fs)	Pathogenic
2762841	NM_014956.5(CEP164):c.349_352del (p.Glu117fs)	Pathogenic
2773025	NM_014956.5(CEP164):c.1257del (p.Ser420fs)	Pathogenic

SpliceAI

6044 predictions. Top by Δscore:

Variant	Effect	Δscore
11:117344151:T:TA	acceptor_gain	1.0000
11:117344161:TGCA:T	acceptor_loss	1.0000
11:117344162:GCA:G	acceptor_loss	1.0000
11:117344164:A:AG	acceptor_gain	1.0000
11:117344164:AGA:A	acceptor_loss	1.0000
11:117344165:G:GA	acceptor_gain	1.0000
11:117344165:GA:G	acceptor_gain	1.0000
11:117344165:GAA:G	acceptor_gain	1.0000
11:117344165:GAAA:G	acceptor_gain	1.0000
11:117344165:GAAAT:G	acceptor_gain	1.0000
11:117344273:CCATG:C	donor_gain	1.0000
11:117344274:CATG:C	donor_gain	1.0000
11:117344275:ATG:A	donor_gain	1.0000
11:117344276:TG:T	donor_gain	1.0000
11:117344277:GG:G	donor_gain	1.0000
11:117344278:G:C	donor_loss	1.0000
11:117344278:G:GG	donor_gain	1.0000
11:117359419:T:G	acceptor_gain	1.0000
11:117361831:ACAG:A	acceptor_gain	1.0000
11:117361990:GCTG:G	donor_gain	1.0000
11:117361994:G:GC	donor_loss	1.0000
11:117361995:T:G	donor_loss	1.0000
11:117362525:A:T	donor_gain	1.0000
11:117362536:CAG:C	donor_loss	1.0000
11:117362537:AG:A	donor_loss	1.0000
11:117362538:GG:G	donor_loss	1.0000
11:117362539:G:C	donor_loss	1.0000
11:117362540:T:A	donor_loss	1.0000
11:117371462:GCCAA:G	donor_gain	1.0000
11:117371463:CCAAG:C	donor_loss	1.0000

AlphaMissense

9555 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:117344267:T:A	W62R	0.999
11:117344267:T:C	W62R	0.999
11:117344269:G:C	W62C	0.999
11:117344269:G:T	W62C	0.999
11:117344181:C:A	A33D	0.998
11:117351818:T:C	F75L	0.998
11:117351819:T:C	F75S	0.998
11:117351820:C:A	F75L	0.998
11:117351820:C:G	F75L	0.998
11:117351847:G:C	W84C	0.998
11:117351847:G:T	W84C	0.998
11:117351853:T:A	H86Q	0.997
11:117351853:T:G	H86Q	0.997
11:117351812:T:G	Y73D	0.996
11:117351815:T:G	Y74D	0.996
11:117351845:T:A	W84R	0.996
11:117351845:T:C	W84R	0.996
11:117344177:T:C	F32L	0.995
11:117344179:T:A	F32L	0.995
11:117344179:T:G	F32L	0.995
11:117344240:G:C	G53R	0.995
11:117344276:T:C	C65R	0.995
11:117351790:C:G	C65W	0.995
11:117409947:T:A	W1360R	0.995
11:117409947:T:C	W1360R	0.995
11:117344220:T:C	L46P	0.994
11:117344229:T:C	L49P	0.994
11:117344235:G:C	R51P	0.994
11:117344268:G:C	W62S	0.994
11:117351792:A:C	Q66P	0.994

dbSNP variants (sampled 300 via entrez): RS1000056575 (11:117377852 CTTTCT>C), RS1000098569 (11:117351061 T>G), RS1000109455 (11:117408797 A>T), RS1000119791 (11:117393388 C>T), RS1000194354 (11:117360287 C>A), RS1000240623 (11:117399092 G>A), RS1000240645 (11:117403127 G>T), RS1000292872 (11:117399341 C>T), RS1000319217 (11:117411071 T>A,C), RS1000335492 (11:117346759 G>A,T), RS1000370201 (11:117326514 T>C), RS1000481788 (11:117320306 A>C), RS1000527861 (11:117404309 T>C), RS1000547760 (11:117341145 A>T), RS1000578008 (11:117401858 AT>A,ATT)

Disease associations

OMIM: gene MIM:614848 | disease phenotypes: MIM:614845, MIM:266900, MIM:256100

GenCC curated gene-disease

Disease	Classification	Inheritance
nephronophthisis 15	Definitive	Autosomal recessive
Senior-Loken syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
CEP164-related ciliopathy	Definitive	AR

Mondo (4): nephronophthisis 15 (MONDO:0013917), inherited retinal dystrophy (MONDO:0019118), Senior-Loken syndrome (MONDO:0017842), nephronophthisis (MONDO:0019005)

Orphanet (3): Senior-Loken syndrome (Orphanet:3156), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Nephronophthisis (Orphanet:655)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000090	Nephronophthisis
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000546	Retinal degeneration
HP:0000556	Retinal dystrophy
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001513	Obesity
HP:0002612	Congenital hepatic fibrosis
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003774	Stage 5 chronic kidney disease
HP:0004322	Short stature
HP:0004348	Abnormality of bone mineral density
HP:0007703	Abnormal retinal pigmentation
HP:0008209	Premature ovarian insufficiency
HP:0010442	Polydactyly
HP:0010579	Cone-shaped epiphysis
HP:0012622	Chronic kidney disease

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004278_9	Pulse pressure	3.000000e-13
GCST006993_11	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07
GCST007096_178	Pulse pressure	7.000000e-17
GCST007097_145	Pulse pressure	2.000000e-06
GCST007097_146	Pulse pressure	1.000000e-09
GCST007097_44	Pulse pressure	9.000000e-06
GCST007268_42	Diastolic blood pressure	1.000000e-09
GCST007269_310	Pulse pressure	2.000000e-25
GCST007637_53	Diffusing capacity of carbon monoxide	9.000000e-06
GCST009391_1782	Metabolite levels	3.000000e-07
GCST010083_277	Hemoglobin levels	7.000000e-11
GCST010241_388	Apolipoprotein A1 levels	7.000000e-10
GCST90002383_43	Hematocrit	4.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0005035	hippocampal volume
EFO:0006336	diastolic blood pressure
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0004468	glucose measurement
EFO:0010477	fructose measurement
EFO:0010481	galactose measurement
EFO:0004509	hemoglobin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004348	hematocrit

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C537580	Senior Loken Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects expression	1
Caffeine	decreases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Endosulfan	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Urethane	increases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
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]
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
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality