CROCC

Summary

CROCC (ciliary rootlet coiled-coil, rootletin, HGNC:21299) is a protein-coding gene on chromosome 1p36.13, encoding Rootletin (Q5TZA2). Major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells which originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus.

Predicted to enable kinesin binding activity and structural molecule activity. Involved in several processes, including centriole-centriole cohesion; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in several cellular components, including actin cytoskeleton; cytosol; and microtubule organizing center.

Source: NCBI Gene 9696 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 586 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_014675

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21299
Approved symbol	CROCC
Name	ciliary rootlet coiled-coil, rootletin
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	rootletin, ROLT, CROCC1
Ensembl gene	ENSG00000058453
Ensembl biotype	protein_coding
OMIM	615776
Entrez	9696

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 protein_coding, 7 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000375541, ENST00000445545, ENST00000465021, ENST00000465291, ENST00000466256, ENST00000467715, ENST00000467938, ENST00000477773, ENST00000486318, ENST00000492631, ENST00000494191, ENST00000497654, ENST00000498688, ENST00000937402, ENST00000937403, ENST00000937404

RefSeq mRNA: 1 — MANE Select: NM_014675 NM_014675

CCDS: CCDS30616

Canonical transcript exons

ENST00000375541 — 37 exons

Exon	Start	End
ENSE00000753547	16971465	16971647
ENSE00000753550	16970636	16970767
ENSE00000753556	16969116	16969340
ENSE00000753562	16965999	16966119
ENSE00000753564	16965723	16965892
ENSE00000753566	16960758	16961130
ENSE00000753568	16958583	16958750
ENSE00000753570	16955997	16956156
ENSE00000753573	16955312	16955550
ENSE00000753576	16954734	16954877
ENSE00000753585	16950953	16951122
ENSE00001620626	16922663	16922798
ENSE00001631764	16924325	16924479
ENSE00001810723	16972360	16972964
ENSE00002216276	16921931	16922078
ENSE00003470184	16948799	16948926
ENSE00003500992	16948331	16948524
ENSE00003506834	16936637	16936873
ENSE00003510882	16931291	16931397
ENSE00003514254	16946259	16946405
ENSE00003516269	16937641	16937737
ENSE00003525292	16970253	16970453
ENSE00003538498	16954223	16954357
ENSE00003543655	16930429	16930594
ENSE00003564850	16938909	16939142
ENSE00003602341	16930286	16930347
ENSE00003634870	16969785	16969934
ENSE00003649335	16966408	16966571
ENSE00003652386	16968203	16968418
ENSE00003669098	16946761	16946991
ENSE00003673634	16945462	16945606
ENSE00003684908	16938400	16938483
ENSE00003688461	16944100	16944282
ENSE00003712356	16929846	16930031
ENSE00003742258	16953302	16953481
ENSE00003745832	16930124	16930207
ENSE00003786362	16939894	16940093

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 98.98.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3845 / max 162.4344, expressed in 368 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
978	1.8380	316
977	0.4181	169
976	0.1284	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.98	gold quality
sural nerve	UBERON:0015488	98.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.73	gold quality
cerebellar hemisphere	UBERON:0002245	96.60	gold quality
cerebellar cortex	UBERON:0002129	96.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.14	gold quality
cerebellum	UBERON:0002037	94.03	gold quality
granulocyte	CL:0000094	93.91	gold quality
apex of heart	UBERON:0002098	93.59	gold quality
right ovary	UBERON:0002118	93.58	gold quality
endocervix	UBERON:0000458	93.49	gold quality
left uterine tube	UBERON:0001303	93.39	gold quality
body of uterus	UBERON:0009853	93.24	gold quality
skin of abdomen	UBERON:0001416	93.00	gold quality
left ovary	UBERON:0002119	92.97	gold quality
ectocervix	UBERON:0012249	92.77	gold quality
tibial nerve	UBERON:0001323	92.26	gold quality
mucosa of stomach	UBERON:0001199	92.09	gold quality
ventricular zone	UBERON:0003053	91.97	gold quality
right lobe of liver	UBERON:0001114	91.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.65	gold quality
body of stomach	UBERON:0001161	91.64	gold quality
metanephros cortex	UBERON:0010533	91.64	gold quality
skin of leg	UBERON:0001511	91.55	gold quality
diaphragm	UBERON:0001103	91.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.39	gold quality
lower esophagus mucosa	UBERON:0035834	91.31	gold quality
adenohypophysis	UBERON:0002196	91.22	gold quality
body of pancreas	UBERON:0001150	91.14	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.26
E-GEOD-100618	no	6.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting CROCC, 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-3613-3P	100.00	76.36	7965
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-1288-3P	96.86	66.95	536

Literature-anchored findings (GeneRIF, showing 9)

• Our findings suggest that the HTLV-I Tax oncoprotein targets TAX1BP2 causing genomic instability and aneuploidy. (PMID:16767081)
• we demonstrated that TAX1BP2 was frequently underexpressed in hepatocellular carcinoma (HCC) and that loss of TAX1BP2 promoted the growth of HCC cells by suppressing activation of the p38/p53/p21 pathway. (PMID:22610972)
• C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis. (PMID:23070519)
• Data show that serine-922 of TAX1BP2 protein is the phosphorylation site of ataxia telangiectasia mutated (ATM) kinase. (PMID:24240686)
• It has been proposed that the archetypal linker protein Rootletin maintains centrosome cohesion in part through inhibition of VHL-mediated Cep68 degradation. (PMID:28089774)
• CEP68 is important in forming rootletin filaments that branch off centrioles and to modulate the thickness of rootletin fibers. (PMID:29463719)
• Rootletin forms large, diffusionally stable bifurcating fibers, which amass slowly on mature centrioles over many hours from anaphase. Nascent centrioles (procentrioles), in contrast, do not form roots and must be licensed to do so through PLK1 activity. (PMID:29649211)
• Up-regulated microRNA-33b inhibits epithelial-mesenchymal transition in gallbladder cancer through down-regulating CROCC. (PMID:31799620)
• Identification of a Structurally Dynamic Domain for Oligomer Formation in Rootletin. (PMID:32325071)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Crocc	ENSMUSG00000040860
rattus_norvegicus	Crocc	ENSRNOG00000008334

Paralogs (4): CEP250 (ENSG00000126001), TSGA10 (ENSG00000135951), CEP135 (ENSG00000174799), CROCC2 (ENSG00000226321)

Protein

Protein identifiers

Rootletin — Q5TZA2 (reviewed: Q5TZA2)

Alternative names: Ciliary rootlet coiled-coil protein

All UniProt accessions (4): Q5TZA2, A0A087WU09, A0A087WW81, B1AKD8

UniProt curated annotations — full annotation on UniProt →

Function. Major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells which originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus. Furthermore, is required for the correct positioning of the cilium basal body relative to the cell nucleus, to allow for ciliogenesis. Contributes to centrosome cohesion before mitosis.

Subunit / interactions. Homomer. Interacts with KLC3, NEK2 and the N-terminus of CEP250. Interacts with CEP44. Interacts with CCDC102B (via N-terminus).

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

Post-translational modifications. Phosphorylated by NEK2 which may regulate its association with centrosomes.

Similarity. Belongs to the rootletin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TZA2-1	1	yes
Q5TZA2-2	2

RefSeq proteins (1): NP_055490* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR055167	Rootletin-like_CC	Domain

Pfam: PF15035

UniProt features (34 total): modified residue 9, sequence variant 7, compositionally biased region 5, coiled-coil region 5, region of interest 4, splice variant 2, chain 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6L5H	X-RAY DIFFRACTION	1.3
6L5J	X-RAY DIFFRACTION	2.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TZA2-F1	69.58	0.00

Functional residue map

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

Post-translational modifications (9): 1460, 1470, 1476, 1483, 1486, 1490, 1496, 1575, 1660

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, MODULE_99, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_ORGANELLE_ASSEMBLY, BROWNE_HCMV_INFECTION_24HR_DN

GO Biological Process (13): centrosome cycle (GO:0007098), intracellular protein localization (GO:0008104), centriole-centriole cohesion (GO:0010457), epithelial structure maintenance (GO:0010669), cellular homeostasis (GO:0019725), ciliary basal body organization (GO:0032053), photoreceptor cell maintenance (GO:0045494), positive regulation of cilium assembly (GO:0045724), establishment of localization in cell (GO:0051649), establishment of organelle localization (GO:0051656), positive regulation of protein localization to cilium (GO:1903566), cell projection organization (GO:0030030), protein localization to organelle (GO:0033365)

GO Molecular Function (5): actin binding (GO:0003779), structural molecule activity (GO:0005198), structural constituent of cytoskeleton (GO:0005200), kinesin binding (GO:0019894), protein binding (GO:0005515)

GO Cellular Component (18): photoreceptor inner segment (GO:0001917), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), ciliary rootlet (GO:0035253), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), glial cell projection (GO:0097386), subapical part of cell (GO:0120219), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995), 9+2 motile cilium (GO:0097729)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
cytoskeleton	3
microtubule organizing center	3
cilium	3
cell cycle process	2
microtubule organizing center organization	2
establishment of localization	2
cytoskeletal protein binding	2
intracellular membraneless organelle	2
plasma membrane bounded cell projection	2
macromolecule localization	1
centrosome cycle	1
tissue homeostasis	1
homeostatic process	1
cilium organization	1
retina homeostasis	1
multicellular organismal process	1
cilium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
cellular localization	1
organelle localization	1
protein localization to cilium	1
regulation of protein localization to cilium	1
positive regulation of protein localization	1
cellular component organization	1
intracellular protein localization	1
molecular_function	1
structural molecule activity	1
cytoskeleton organization	1
binding	1
centriole	1
cytoplasm	1
membrane	1
cell periphery	1
extracellular vesicle	1
sperm flagellum	1
intracellular anatomical structure	1
intraciliary transport particle	1

Protein interactions and networks

STRING

2212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CROCC	LRRC45	Q96CN5	981
CROCC	CNTLN	Q9NXG0	922
CROCC	CEP250	Q9BV73	899
CROCC	NEK2	P51955	883
CROCC	CDK5RAP2	Q96SN8	789
CROCC	CEP135	Q66GS9	715
CROCC	SASS6	Q6UVJ0	712
CROCC	MLF2	Q15773	705
CROCC	PCNT	O95613	685
CROCC	NEK11	Q8NG66	675
CROCC	NIN	Q8N4C6	604
CROCC	CEP164	Q9UPV0	598
CROCC	OFD1	O75665	588
CROCC	BBS4	Q96RK4	584
CROCC	CNTROB	Q8N137	584

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
SCGN	SNAP23	psi-mi:“MI:0914”(association)	0.550
G3BP1	COX5A	psi-mi:“MI:0914”(association)	0.530
EPS15L1	NDC80	psi-mi:“MI:0914”(association)	0.530
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
CROCC	GAPDH	psi-mi:“MI:0915”(physical association)	0.400
CROCC	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
RNF152	CROCC	psi-mi:“MI:0915”(physical association)	0.370
Magoh	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
CEP152	WDR62	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SCGN	SNAP23	psi-mi:“MI:0914”(association)	0.350
TPM1	SPAG9	psi-mi:“MI:0914”(association)	0.350
CROCC	PEX14	psi-mi:“MI:0914”(association)	0.350
RALBP1	AP2A1	psi-mi:“MI:0914”(association)	0.350
HDAC1	ZBTB43	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	SPTBN2	psi-mi:“MI:0914”(association)	0.350
CNTROB	DLAT	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CEP152	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
CCP110	KIF2A	psi-mi:“MI:0914”(association)	0.350
POC5	PDHX	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): CROCC (Affinity Capture-MS), CROCC (Affinity Capture-MS), CROCC (Affinity Capture-MS), CROCC (Affinity Capture-MS), CROCC (Affinity Capture-MS), CROCC (Affinity Capture-MS), CROCC (Affinity Capture-MS), CROCCP2 (Affinity Capture-MS), XBP1 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), CROCC (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), SRBD1 (Affinity Capture-MS), CROCC (Affinity Capture-MS), CROCC (Affinity Capture-MS)

ESM2 similar proteins: A0JNH6, A0JNT9, A1A5D9, A7YH32, A7YWC8, A9QT41, A9X1A5, B0KWC9, B1MTG4, B3EX63, E1U8D0, O75145, O75335, P55937, P58660, P59242, P60469, Q08378, Q2KJ21, Q2TAC2, Q3LUD3, Q3TMW1, Q3UHU5, Q3UMT1, Q4QRL3, Q5TZA2, Q60952, Q6DFL0, Q6NZW0, Q6PGZ0, Q6PHN1, Q6QZQ4, Q6ZP65, Q8BP01, Q8C7U1, Q8CHW5, Q8CJ40, Q8K2I2, Q8N137, Q8TF21

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

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CDK2	down-regulates	CROCC	phosphorylation
LRRC45	“up-regulates activity”	CROCC	binding
CROCC	down-regulates	Centrosome_separation
CCDC102B	“up-regulates activity”	CROCC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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.

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	6	86.2×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	485
Likely benign	42
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
980391	GRCh37/hg19 1p36.13-36.12(chr1:17284906-21778495)x1	Pathogenic

SpliceAI

6752 predictions. Top by Δscore:

Variant	Effect	Δscore
1:16922758:G:GT	donor_gain	1.0000
1:16924323:A:AG	acceptor_gain	1.0000
1:16924324:G:GG	acceptor_gain	1.0000
1:16924450:GCCAT:G	donor_gain	1.0000
1:16924454:T:G	donor_gain	1.0000
1:16924454:T:TG	donor_gain	1.0000
1:16924458:G:GG	donor_gain	1.0000
1:16924476:GAGG:G	donor_gain	1.0000
1:16924478:GG:G	donor_gain	1.0000
1:16924479:GG:G	donor_gain	1.0000
1:16929844:A:AG	acceptor_gain	1.0000
1:16929845:G:GG	acceptor_gain	1.0000
1:16929984:G:GT	donor_gain	1.0000
1:16930028:C:T	donor_gain	1.0000
1:16930028:CAAG:C	donor_loss	1.0000
1:16930029:AAG:A	donor_loss	1.0000
1:16930030:AGG:A	donor_loss	1.0000
1:16930031:GGTC:G	donor_loss	1.0000
1:16930119:CCCA:C	acceptor_loss	1.0000
1:16930120:CCA:C	acceptor_loss	1.0000
1:16930122:A:AG	acceptor_gain	1.0000
1:16930122:AGAT:A	acceptor_loss	1.0000
1:16930123:G:GG	acceptor_gain	1.0000
1:16930202:C:G	donor_gain	1.0000
1:16930206:GG:G	donor_gain	1.0000
1:16930207:GG:G	donor_gain	1.0000
1:16930280:A:AG	acceptor_gain	1.0000
1:16930281:C:G	acceptor_gain	1.0000
1:16930281:CCCA:C	acceptor_loss	1.0000
1:16930284:A:AC	acceptor_loss	1.0000

AlphaMissense

12794 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:16930021:T:C	L176P	0.992
1:16930461:T:A	L239H	0.989
1:16930461:T:C	L239P	0.988
1:16924415:T:C	L96P	0.983
1:16929970:T:C	L159P	0.983
1:16930009:T:C	L172P	0.983
1:16954223:G:C	A1063P	0.983
1:16953441:G:C	R1049P	0.982
1:16930464:G:C	R240P	0.981
1:16924432:G:C	A102P	0.980
1:16930002:G:C	A170P	0.979
1:16929997:G:C	R168P	0.978
1:16953461:G:C	A1056P	0.978
1:16956137:T:C	L1282P	0.978
1:16929968:G:C	K158N	0.977
1:16929968:G:T	K158N	0.977
1:16931339:T:A	W300R	0.975
1:16931339:T:C	W300R	0.975
1:16924397:T:C	L90P	0.974
1:16924439:G:C	R104P	0.974
1:16953453:T:C	L1053P	0.974
1:16955544:G:C	R1233P	0.974
1:16954257:T:C	L1074P	0.973
1:16955511:T:C	L1222P	0.973
1:16930440:T:C	L232P	0.970
1:16930329:T:C	L222P	0.969
1:16930473:T:C	L243P	0.969
1:16931341:G:C	W300C	0.969
1:16931341:G:T	W300C	0.969
1:16930138:G:C	K184N	0.968

dbSNP variants (sampled 300 via entrez): RS1000179201 (1:16926884 C>A), RS1000422112 (1:16943142 T>G), RS1000437740 (1:16953205 G>A,C), RS1000717614 (1:16926284 C>T), RS1000726527 (1:16964090 C>T), RS1000755117 (1:16946793 G>A,T), RS1000871439 (1:16969597 T>G), RS1000913203 (1:16931077 A>G), RS1000972851 (1:16958469 G>A,C), RS1001019345 (1:16913761 T>C,G), RS1001075354 (1:16971281 G>A), RS1001156421 (1:16913146 G>A), RS1001169573 (1:16945246 A>G), RS1001296616 (1:16968427 C>G,T), RS1001377609 (1:16959731 A>G)

Disease associations

OMIM: gene MIM:615776 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): breast ductal adenocarcinoma (MONDO:0005590), premature menopause (MONDO:0001119)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001310_7	Allergic rhinitis	4.000000e-06
GCST008161_23	Waist circumference adjusted for body mass index	6.000000e-06
GCST010696_16	Cortical thickness (min-P)	8.000000e-11
GCST010697_21	Cortical surface area (min-P)	1.000000e-08
GCST010698_46	Subcortical volume (min-P)	2.000000e-11
GCST010699_5	Brain morphology (min-P)	7.000000e-11
GCST010700_46	Cortical thickness (MOSTest)	2.000000e-10
GCST010701_63	Cortical surface area (MOSTest)	3.000000e-14
GCST010702_161	Subcortical volume (MOSTest)	2.000000e-20
GCST010703_70	Brain morphology (MOSTest)	2.000000e-08
GCST90002383_147	Hematocrit	8.000000e-11
GCST90002389_78	Lymphocyte percentage of white cells	3.000000e-09
GCST90002403_34	Red blood cell count	1.000000e-09
GCST90020027_1774	Waist-hip index	5.000000e-08
GCST90020029_1242	Waist circumference adjusted for body mass index	6.000000e-21

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004348	hematocrit
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067443 (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
6.97	Kd	106.7	nM	CHEMBL3752910
6.94	ED50	115.4	nM	CHEMBL3752910

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149845: Binding affinity to human CROCC incubated for 45 mins by Kinobead based pull down assay	kd	0.1067	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
bisphenol A	increases methylation	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Sunitinib	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dinitrochlorobenzene	affects binding	1
Folic Acid	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Polychlorinated Biphenyls	affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases 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
CHEMBL5652887	Binding	Binding affinity to human CROCC 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)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation