CEP170

Summary

CEP170 (centrosomal protein 170, HGNC:28920) is a protein-coding gene on chromosome 1q43, encoding Centrosomal protein of 170 kDa (Q5SW79). Plays a role in microtubule organization.

The product of this gene is a component of the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. During interphase, the encoded protein localizes to the sub-distal appendages of mature centrioles, which are microtubule-based structures thought to help organize centrosomes. During mitosis, the protein associates with spindle microtubules near the centrosomes. The protein interacts with and is phosphorylated by polo-like kinase 1, and functions in maintaining microtubule organization and cell morphology. The human genome contains a putative transcribed pseudogene. Several alternatively spliced transcript variants of this gene have been found, but the full-length nature of some of these variants has not been determined.

Source: NCBI Gene 9859 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 243 total — 4 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_014812

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28920
Approved symbol	CEP170
Name	centrosomal protein 170
Location	1q43
Locus type	gene with protein product
Status	Approved
Aliases	KAB, FAM68A
Ensembl gene	ENSG00000143702
Ensembl biotype	protein_coding
OMIM	613023
Entrez	9859

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 18 protein_coding, 6 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000336415, ENST00000366542, ENST00000366543, ENST00000366544, ENST00000413359, ENST00000439296, ENST00000451408, ENST00000461671, ENST00000464936, ENST00000466495, ENST00000468254, ENST00000468697, ENST00000469646, ENST00000476661, ENST00000481987, ENST00000490813, ENST00000492145, ENST00000518289, ENST00000521911, ENST00000522191, ENST00000522522, ENST00000522895, ENST00000522995, ENST00000523424, ENST00000523581, ENST00000884285, ENST00000884286, ENST00000931982, ENST00000931983, ENST00000956795

RefSeq mRNA: 3 — MANE Select: NM_014812 NM_001042404, NM_001042405, NM_014812

CCDS: CCDS44337, CCDS44338, CCDS44339

Canonical transcript exons

ENST00000366542 — 20 exons

Exon	Start	End
ENSE00001441972	243124428	243126738
ENSE00002267089	243139937	243140107
ENSE00002276695	243142316	243142463
ENSE00002376455	243186259	243186422
ENSE00002381369	243164284	243166116
ENSE00002388936	243191018	243191494
ENSE00002400828	243199060	243199194
ENSE00002409520	243200518	243200680
ENSE00002415162	243255040	243255281
ENSE00002426571	243211886	243211964
ENSE00003482187	243225176	243225321
ENSE00003524184	243185779	243186072
ENSE00003543150	243128249	243128300
ENSE00003568543	243221724	243221813
ENSE00003580422	243172697	243172846
ENSE00003596129	243156221	243156455
ENSE00003649313	243136143	243136231
ENSE00003676501	243169628	243169754
ENSE00003784121	243129360	243129453
ENSE00003787852	243200777	243200835

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.5478 / max 901.9458, expressed in 1816 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18331	29.1839	1788
18329	3.2463	1293
18340	3.0754	1329
18332	2.5905	1200
18339	0.9326	438
18333	0.6853	411
18335	0.5713	347
18328	0.5434	278
18336	0.4416	227
18330	0.3610	169

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.54	gold quality
ganglionic eminence	UBERON:0004023	99.23	gold quality
corpus callosum	UBERON:0002336	98.92	gold quality
ventricular zone	UBERON:0003053	98.52	gold quality
left testis	UBERON:0004533	97.38	gold quality
right testis	UBERON:0004534	97.24	gold quality
sural nerve	UBERON:0015488	96.91	gold quality
testis	UBERON:0000473	96.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.42	gold quality
colonic epithelium	UBERON:0000397	95.98	gold quality
calcaneal tendon	UBERON:0003701	95.38	gold quality
cerebellar cortex	UBERON:0002129	95.22	gold quality
cerebellar hemisphere	UBERON:0002245	95.18	gold quality
cerebellum	UBERON:0002037	95.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.75	gold quality
stromal cell of endometrium	CL:0002255	94.52	gold quality
superior frontal gyrus	UBERON:0002661	94.44	gold quality
bone marrow	UBERON:0002371	94.41	gold quality
primary visual cortex	UBERON:0002436	93.76	gold quality
prefrontal cortex	UBERON:0000451	93.33	gold quality
bone marrow cell	CL:0002092	93.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.20	gold quality
substantia nigra	UBERON:0002038	93.08	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.89	gold quality
adrenal tissue	UBERON:0018303	92.89	gold quality
hypothalamus	UBERON:0001898	92.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.09	gold quality
frontal cortex	UBERON:0001870	92.05	gold quality
cerebral cortex	UBERON:0000956	92.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.96	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.80
E-ANND-3	yes	5.88
E-CURD-112	yes	5.65
E-GEOD-99795	no	89.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

150 targeting CEP170, 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-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 7)

• Cep170 interacts with Polo-like kinase 1 in mature centrioles. (PMID:15616186)
• Data indicate that Cep170 association with the C-terminus of Kif2b enhances localization of Kif2b to the spindle. (PMID:23087211)
• Data suggest that CDK5RAP2 and CEP170 both interact with microtubule nucleation-promoting region of AKAP350A; CEP68 interacts with distal C-terminal region of AKAP350A; AKAP350A spans the bridge between centrioles. (CDK5RAP2 = CDK5 regulatory subunit associated protein 2; CEP170 = centrosomal protein 170kDa; AKAP350A = A kinase (PRKA) anchor protein (yotiao) 9; CEP68 = centrosomal protein 68kDa) (PMID:29054927)
• Ccdc61 controls centrosomal localization of Cep170 and is required for spindle assembly and symmetry. (PMID:30354798)
• SEPT1 function depends on the Golgi matrix protein GOLGA2 and on centrosomal proteins, including CEP170 and components of gamma-tubulin ring complex, to facilitate the perinuclear concentration of Golgi membranes. (PMID:30709970)
• Study in mutant mice and human cerebral organoids showed that WDR62 deletion resulted in a reduction in the size of mouse brains and organoids due to the disruption of neural progenitor cells. WDR62 interacts with and promotes CEP170 localization to the basal body of primary cilium, where CEP170 recruits KIF2A to disassemble cilium. (PMID:31197141)
• alpha-/gamma-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization. (PMID:35119360)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep170aa	ENSDARG00000006128
mus_musculus	Cep170	ENSMUSG00000057335
rattus_norvegicus	Cep170	ENSRNOG00000004127

Paralogs (1): CEP170B (ENSG00000099814)

Protein

Protein identifiers

Centrosomal protein of 170 kDa — Q5SW79 (reviewed: Q5SW79)

Alternative names: KARP-1-binding protein

All UniProt accessions (12): Q5SW79, E5RFU8, E5RG47, E5RGW7, E5RIH6, E5RJT5, E7EMW0, E7EWM2, H0Y2V6, H0Y4T4, H0YB66, H0YB92

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in microtubule organization. Required for centriole subdistal appendage assembly.

Subunit / interactions. Interacts with CCDC68 and CCDC120; leading to recruitment to centrosomes. Interacts with PLK1. Interacts with NIN. Interacts with FHDC1. Interacts with CCDC61. Interacts with TBK1; efficient complex formation may be dependent on the presence of CCDC61.

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

Post-translational modifications. Phosphorylated; probably by PLK1.

Similarity. Belongs to the CEP170 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5SW79-1	1, Alpha	yes
Q5SW79-2	2, Gamma, 3
Q5SW79-3	3, Beta, KAB2

RefSeq proteins (3): NP_001035863, NP_001035864, NP_055627* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR029300	CEP170_C	Domain
IPR051176	Cent_Immune-Sig_Mod	Family

Pfam: PF00498, PF15308

UniProt features (96 total): modified residue 48, compositionally biased region 18, region of interest 11, strand 9, splice variant 3, helix 2, chain 1, domain 1, coiled-coil region 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4JON	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SW79-F1	46.25	0.07

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 (48): 138, 141, 356, 359, 364, 446, 466, 497, 501, 571, 580, 630, 633, 636, 644, 667, 725, 760, 838, 879 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 235 (showing top): GCM_ZNF198, GCM_PPM1D, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOZGIT_ESR1_TARGETS_UP, GCM_SUFU, DODD_NASOPHARYNGEAL_CARCINOMA_UP, ATCATGA_MIR433, SENESE_HDAC1_TARGETS_UP, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, BECKER_TAMOXIFEN_RESISTANCE_DN, chr1q43, TTTGCAC_MIR19A_MIR19B, GCM_MAP1B

GO Biological Process (0):

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

GO Cellular Component (10): centrosome (GO:0005813), centriole (GO:0005814), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), ciliary basal body (GO:0036064), centriolar subdistal appendage (GO:0120103), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule organizing center	3
intracellular membraneless organelle	3
cellular anatomical structure	3
microtubule cytoskeleton	2
cilium	2
binding	1
centriole	1
cytoplasm	1
polymeric cytoskeletal fiber	1
intracellular protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP170	CEP128	Q6ZU80	970
CEP170	CNTRL	Q7Z7A1	943
CEP170	NIN	Q8N4C6	878
CEP170	CNTLN	Q9NXG0	878
CEP170	CCDC120	Q96HB5	806
CEP170	PLK1	P53350	789
CEP170	KIF2B	Q8N4N8	788
CEP170	CCDC68	Q9H2F9	778
CEP170	KIFC3	Q9BVG8	744
CEP170	TUBE1	Q9UJT0	738
CEP170	PCNT	O95613	731
CEP170	CEP164	Q9UPV0	720
CEP170	KIF2A	O00139	684
CEP170	SCLT1	Q96NL6	641
CEP170	CEP89	Q96ST8	635

IntAct

335 interactions, top by confidence:

A	B	Type	Score
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
CCDC120	CEP170	psi-mi:“MI:0403”(colocalization)	0.820
CCDC120	CEP170	psi-mi:“MI:0914”(association)	0.820
CEP170	CCDC120	psi-mi:“MI:0915”(physical association)	0.820
CCDC120	CEP170	psi-mi:“MI:0915”(physical association)	0.820
CCDC120	CEP170	psi-mi:“MI:0407”(direct interaction)	0.820
CEP170	CCDC120	psi-mi:“MI:0914”(association)	0.820
CEP170	CCDC120	psi-mi:“MI:0403”(colocalization)	0.820
CCDC68	CEP170	psi-mi:“MI:0915”(physical association)	0.810
CCDC68	CEP170	psi-mi:“MI:0403”(colocalization)	0.810
DISC1	CEP170	psi-mi:“MI:0915”(physical association)	0.750
TEKT2	CEP170	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CEP170P1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.670
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
CCDC68	NDC80	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
CCDC120	ODF2	psi-mi:“MI:0403”(colocalization)	0.600
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540

BioGRID (490): CEP170 (Affinity Capture-MS), CEP170 (Affinity Capture-MS), CEP170 (Affinity Capture-MS), PCYT1A (Affinity Capture-MS), SYNE2 (Affinity Capture-MS), AKAP9 (Affinity Capture-MS), KIFC3 (Affinity Capture-MS), PSPC1 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), ASB7 (Affinity Capture-MS), NIN (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), CEP170P1 (Affinity Capture-MS), CEP170B (Affinity Capture-MS), DSTYK (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1B0GVH6, A0A2K1JJ00, A0JM08, A2BIL8, A2RRY8, A4IGV6, B0BK70, B3DHS1, E9Q309, F1QPR4, F1QR98, P32845, P34469, P48437, P97440, Q06616, Q06813, Q1KN21, Q1LV19, Q1RMQ5, Q3ZBS1, Q498L0, Q4JQW6, Q4R309, Q4V7B2, Q5RDK8, Q5SW79, Q5VT06, Q62417, Q62770, Q68FQ8, Q6A065, Q6DFB0, Q6PKN7, Q8K0T7, Q8N9R6, Q8VEB3, Q91018, Q92786

Diamond homologs: A0JM08, Q498L0, Q5M9G6, Q5SW79, Q6A065, Q80U49, Q8BIZ6, Q8TAD8, Q96L14, Q9BWU0, Q9Y4F5, B7SY83, Q07930, Q54VU4, Q8W4D8, B1AJZ9, A0QNG6, P34648, Q12972, Q28147, Q8R3G1, Q9FIK2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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	18	25.5×	1e-18
Loss of proteins required for interphase microtubule organization from the centrosome	18	25.5×	1e-18
Anchoring of the basal body to the plasma membrane	25	25.2×	4e-26
AURKA Activation by TPX2	18	24.5×	2e-18
Recruitment of mitotic centrosome proteins and complexes	18	21.9×	1e-17
Regulation of PLK1 Activity at G2/M Transition	18	20.4×	3e-17
Recruitment of NuMA to mitotic centrosomes	19	19.8×	9e-18
Centrosome maturation	7	15.9×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	9	45.5×	9e-11
protein localization to centrosome	5	23.2×	2e-04
anterograde axonal transport	5	20.0×	4e-04
establishment of mitotic spindle orientation	6	19.9×	8e-05
non-motile cilium assembly	9	18.0×	3e-07
mitotic spindle assembly	6	14.2×	4e-04
mitotic spindle organization	7	13.1×	1e-04
cell projection organization	5	12.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	212
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1047876	GRCh37/hg19 1q43-44(chr1:240554955-247342593)	Pathogenic
2425626	NC_000001.10:g.(?243335979)(243419562_?)del	Pathogenic
4279312	GRCh37/hg19 1q43(chr1:243327925-243499560)x1	Pathogenic
660672	NC_000001.11:g.(?242268256)(243843190_?)del	Pathogenic

SpliceAI

4026 predictions. Top by Δscore:

Variant	Effect	Δscore
1:243126734:GATTG:G	acceptor_gain	1.0000
1:243126735:ATTG:A	acceptor_gain	1.0000
1:243126736:TTG:T	acceptor_gain	1.0000
1:243126737:TG:T	acceptor_gain	1.0000
1:243126738:GC:G	acceptor_loss	1.0000
1:243126739:C:CC	acceptor_gain	1.0000
1:243126739:CTAAA:C	acceptor_loss	1.0000
1:243126747:C:CT	acceptor_gain	1.0000
1:243126748:G:T	acceptor_gain	1.0000
1:243128244:TTTAC:T	donor_loss	1.0000
1:243128247:A:AT	donor_loss	1.0000
1:243128248:C:A	donor_loss	1.0000
1:243129359:CCATG:C	donor_gain	1.0000
1:243129450:TATT:T	acceptor_gain	1.0000
1:243129452:TT:T	acceptor_gain	1.0000
1:243129453:TC:T	acceptor_loss	1.0000
1:243129454:C:CC	acceptor_gain	1.0000
1:243129454:C:T	acceptor_loss	1.0000
1:243129455:T:A	acceptor_loss	1.0000
1:243129462:C:CT	acceptor_gain	1.0000
1:243136139:GTAC:G	donor_loss	1.0000
1:243136142:C:G	donor_loss	1.0000
1:243136164:T:C	donor_gain	1.0000
1:243136180:T:C	donor_gain	1.0000
1:243136228:TGAC:T	acceptor_gain	1.0000
1:243136228:TGACC:T	acceptor_loss	1.0000
1:243136229:GACC:G	acceptor_loss	1.0000
1:243136230:ACCTG:A	acceptor_loss	1.0000
1:243136232:C:CC	acceptor_gain	1.0000
1:243136232:CTG:C	acceptor_loss	1.0000

AlphaMissense

10416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:243128254:A:G	L1487P	1.000
1:243128275:A:G	L1480P	1.000
1:243129425:A:G	W1450R	1.000
1:243129425:A:T	W1450R	1.000
1:243136200:A:T	V1421D	1.000
1:243142428:A:C	I1316S	1.000
1:243142428:A:G	I1316T	1.000
1:243142428:A:T	I1316N	1.000
1:243142431:T:A	E1315V	1.000
1:243142434:C:G	R1314P	1.000
1:243142437:G:T	A1313D	1.000
1:243142438:C:G	A1313P	1.000
1:243142440:A:T	I1312N	1.000
1:243142447:C:G	A1310P	1.000
1:243142449:A:G	L1309P	1.000
1:243142449:A:T	L1309H	1.000
1:243142452:T:A	D1308V	1.000
1:243142452:T:C	D1308G	1.000
1:243142452:T:G	D1308A	1.000
1:243142457:G:C	S1306R	1.000
1:243142457:G:T	S1306R	1.000
1:243142458:C:A	S1306I	1.000
1:243142459:T:G	S1306R	1.000
1:243142461:A:C	I1305S	1.000
1:243142461:A:G	I1305T	1.000
1:243156224:G:T	A1303D	1.000
1:243156225:C:G	A1303P	1.000
1:243156227:A:C	I1302R	1.000
1:243156227:A:T	I1302K	1.000
1:243156247:C:A	W1295C	1.000

dbSNP variants (sampled 300 via entrez): RS1000057098 (1:243221075 A>C,G), RS1000161953 (1:243189485 G>A), RS1000165258 (1:243234349 C>G,T), RS1000241375 (1:243245191 A>G), RS1000257295 (1:243251177 T>A,C), RS1000291787 (1:243182952 A>G), RS1000294404 (1:243233673 C>T), RS1000339433 (1:243257358 C>G), RS1000346608 (1:243175390 T>C), RS1000349832 (1:243128716 G>A,C), RS1000361989 (1:243216408 T>C), RS1000369062 (1:243227928 T>C), RS1000386435 (1:243135195 T>G), RS1000438751 (1:243134823 C>T), RS1000449330 (1:243182506 T>TAA)

Disease associations

OMIM: gene MIM:613023 | disease phenotypes: MIM:217990, MIM:613615, MIM:615993

GenCC curated gene-disease

Mondo (4): microcephaly (MONDO:0001149), corpus callosum, agenesis of (MONDO:0009022), Senior-Loken syndrome 7 (MONDO:0013326), Bardet-Biedl syndrome 16 (MONDO:0014444)

Orphanet (3): Isolated corpus callosum agenesis (Orphanet:200), Bardet-Biedl syndrome (Orphanet:110), Senior-Loken syndrome (Orphanet:3156)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002104_18	Bronchopulmonary dysplasia	3.000000e-06
GCST002149_19	Schizophrenia	2.000000e-08
GCST002929_6	Chromium levels	3.000000e-06
GCST004749_56	Lung cancer in ever smokers	9.000000e-08
GCST006166_18	Diastolic blood pressure x alcohol consumption interaction (2df test)	9.000000e-15
GCST006190_23	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-16
GCST006190_30	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-20
GCST006193_14	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-20
GCST006193_54	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-17
GCST006804_174	Red cell distribution width	2.000000e-08
GCST007876_145	Estimated glomerular filtration rate	2.000000e-11
GCST008027_3	Smoking behaviour (cigarettes smoked per day)	3.000000e-08
GCST008027_4	Smoking behaviour (cigarettes smoked per day)	2.000000e-06
GCST008550_15	Mental health study participation (completed survey)	1.000000e-10
GCST008889_1	Systemising	7.000000e-07
GCST009391_1414	Metabolite levels	6.000000e-06
GCST009391_602	Metabolite levels	5.000000e-06
GCST90002404_5	Red cell distribution width	1.000000e-12

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0009188	Red cell distribution width
EFO:0006525	cigarettes per day measurement
EFO:0010130	health study participation
EFO:0010221	systemising measurement
EFO:0010451	aconitate measurement
EFO:0010505	isocitrate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067343 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.96	Kd	109.2	nM	CHEMBL5653589
6.96	ED50	109.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148060: Binding affinity to human CEP170 incubated for 45 mins by Kinobead based pull down assay	kd	0.1092	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases methylation, increases expression	2
cobaltous chloride	decreases expression, increases expression	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
arsenite	decreases reaction, affects binding	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
bisphenol AF	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Endosulfan	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Piroxicam	increases expression	1
Quercetin	increases phosphorylation	1
Rotenone	increases expression	1
Selenium	decreases expression	1
Trichloroethylene	increases expression	1
Valproic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651102	Binding	Binding affinity to human CEP170 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01678105	PHASE2	COMPLETED	A Phase II Study of Dovitinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands
NCT06066333	PHASE2	RECRUITING	Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma
NCT01898715	PHASE1	COMPLETED	Phase 1 Study of ATR-101 in Subjects With Advanced Adrenocortical Carcinoma
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.
NCT01262235	PHASE1/PHASE2	COMPLETED	A Dose Finding Study of TKM-080301 Infusion in Neuroendocrine Tumors (NET) and Adrenocortical Carcinoma (ACC) Patients
NCT00170326	Not specified	COMPLETED	Progressive Ventricular Dysfunction Prevention in Pacemaker Patients
NCT01117792	Not specified	COMPLETED	Subcutaneous Implantable Defibrillator (S-ICD) System - CE Clinical Investigation
NCT02267161	Not specified	COMPLETED	Infants With Agenesis of the Corpus Callosum
NCT02826824	Not specified	UNKNOWN	BECOME CHILDREN OF HOLDERS Corpus Callosum Agenesis Screened IN PERIOD Antenatal
NCT05843110	Not specified	UNKNOWN	Decision-making Process of Couples Confronted With Prenatal Diagnosis of an Isolated CCA
NCT06262152	Not specified	UNKNOWN	Sleep Profile of Patients With Septo-optic Dysplasia