CEP43

Summary

CEP43 (centrosomal protein 43, HGNC:17012) is a protein-coding gene on chromosome 6q27, encoding Centrosomal protein 43 (O95684). Required for anchoring microtubules to the centrosomes. It is a selective cancer dependency (DepMap: 34.8% of cell lines).

This gene encodes a largely hydrophilic centrosomal protein that is required for anchoring microtubules to subcellular structures. A t(6;8)(q27;p11) chromosomal translocation, fusing this gene and the fibroblast growth factor receptor 1 (FGFR1) gene, has been found in cases of myeloproliferative disorder. The resulting chimeric protein contains the N-terminal leucine-rich region of this encoded protein fused to the catalytic domain of FGFR1. Alterations in this gene may also be associated with Crohn’s disease, Graves’ disease, and vitiligo. Alternatively spliced transcript variants that encode different proteins have been identified.

Source: NCBI Gene 11116 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 98 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 34.8% of screened cell lines
• MANE Select transcript: NM_007045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17012
Approved symbol	CEP43
Name	centrosomal protein 43
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	FOP
Ensembl gene	ENSG00000213066
Ensembl biotype	protein_coding
OMIM	605392
Entrez	11116

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 34 protein_coding, 11 retained_intron, 7 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000349556, ENST00000366847, ENST00000476078, ENST00000488525, ENST00000494781, ENST00000496181, ENST00000622353, ENST00000704900, ENST00000704901, ENST00000704918, ENST00000704959, ENST00000704960, ENST00000704962, ENST00000704982, ENST00000704983, ENST00000704985, ENST00000704986, ENST00000705029, ENST00000705058, ENST00000705059, ENST00000705110, ENST00000705168, ENST00000705169, ENST00000705170, ENST00000705171, ENST00000705172, ENST00000705173, ENST00000705175, ENST00000705176, ENST00000705177, ENST00000705178, ENST00000705179, ENST00000705180, ENST00000705235, ENST00000705236, ENST00000705237, ENST00000705238, ENST00000705239, ENST00000705240, ENST00000705241, ENST00000705242, ENST00000878122, ENST00000878123, ENST00000878124, ENST00000878125, ENST00000878126, ENST00000878127, ENST00000878128, ENST00000878129, ENST00000936349, ENST00000936350, ENST00000936351, ENST00000936352, ENST00000936353, ENST00000953639, ENST00000953640

RefSeq mRNA: 3 — MANE Select: NM_007045 NM_001278690, NM_007045, NM_194429

CCDS: CCDS5296, CCDS5297, CCDS75550

Canonical transcript exons

ENST00000366847 — 13 exons

Exon	Start	End
ENSE00001890814	167039904	167052718
ENSE00002283227	167004264	167004401
ENSE00003608099	167003193	167003247
ENSE00003613868	167003723	167003811
ENSE00003993080	166999397	166999514
ENSE00003993084	167013508	167013567
ENSE00003993107	167032603	167032642
ENSE00003993108	167026547	167026615
ENSE00003993110	167022409	167022635
ENSE00003993111	167010813	167010893
ENSE00003993112	167033875	167033971
ENSE00003993113	167000060	167000113
ENSE00003993114	167024782	167024894

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.4085 / max 366.6815, expressed in 1818 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71177	20.6174	1809
71175	1.9893	1128
71176	1.6499	988
71174	0.1400	50
71178	0.0118	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.35	gold quality
secondary oocyte	CL:0000655	98.32	gold quality
tendon of biceps brachii	UBERON:0008188	96.54	gold quality
male germ cell	CL:0000015	96.32	gold quality
right uterine tube	UBERON:0001302	96.25	gold quality
left testis	UBERON:0004533	95.62	gold quality
oocyte	CL:0000023	95.48	gold quality
right testis	UBERON:0004534	95.44	gold quality
testis	UBERON:0000473	93.97	gold quality
buccal mucosa cell	CL:0002336	92.21	gold quality
endometrium	UBERON:0001295	90.88	gold quality
medial globus pallidus	UBERON:0002477	90.43	gold quality
bronchial epithelial cell	CL:0002328	90.40	gold quality
caput epididymis	UBERON:0004358	90.32	gold quality
right lobe of liver	UBERON:0001114	90.24	gold quality
epithelium of bronchus	UBERON:0002031	89.93	gold quality
bronchus	UBERON:0002185	89.78	gold quality
endothelial cell	CL:0000115	89.28	silver quality
Brodmann (1909) area 23	UBERON:0013554	89.27	gold quality
rectum	UBERON:0001052	89.20	gold quality
fallopian tube	UBERON:0003889	89.05	gold quality
epithelium of nasopharynx	UBERON:0001951	88.82	gold quality
globus pallidus	UBERON:0001875	88.55	gold quality
liver	UBERON:0002107	88.27	gold quality
oviduct epithelium	UBERON:0004804	88.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.98	gold quality
tendon	UBERON:0000043	87.91	gold quality
pons	UBERON:0000988	87.89	gold quality
nephron tubule	UBERON:0001231	87.84	gold quality
mammary duct	UBERON:0001765	87.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting CEP43, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3671	99.90	73.04	3897

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• CAP350 interacts directly with FOP (FGFR1 oncogene partner) to form a centrosomal complex required for microtubule anchoring. (PMID:16314388)
• a 1.6A resolution crystal structure of the N-terminal dimerization domain of FOP. The structure comprises an alpha-helical bundle composed of two antiparallel chains, each of them having five alpha-helices. (PMID:16690081)
• Since FGFR1OP is plays a significant role in lung cancer growth and progression, it may be useful as a prognostic biomarker and as a therapeutic target for lung cancer. (PMID:17888034)
• FOP is a centriolar satellite protein involved in ciliogenesis. (PMID:23554904)
• This study was designed to determine the association of CCR6 and FGFR10P (tag)single nucleotide polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome, in two independent Chinese Han populations. (PMID:23935994)
• The rs151606 T>G was associated with an increased risk of lung cancer and rs12212247 T>C was associated with a decreased risk of lung cancer (PMID:26905588)
• We show that Fop mutation perturbs ciliogenesis in vivo and that this leads to the alteration of the Hedgehog signaling pathway. Fop mutation reduces CSs movements and affects pericentriolar material composition, which probably participates to the ciliogenesis defect. (PMID:29982567)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep43	ENSDARG00000003058
mus_musculus	Cep43	ENSMUSG00000069135
rattus_norvegicus	Cep43	ENSRNOG00000055093

Protein

Protein identifiers

Centrosomal protein 43 — O95684 (reviewed: O95684)

Alternative names: FGFR1 oncogene partner

All UniProt accessions (23): A0A087WV25, A0A994J4R0, A0A994J4R8, A0A994J4T6, A0A994J4U0, A0A994J500, A0A994J505, A0A994J518, A0A994J5D2, A0A994J5E9, A0A994J5F4, A0A994J5F6, A0A994J5H0, A0A994J7B5, A0A994J7B9, A0A994J7C9, A0A994J7D3, A0A994J7Q3, A0A994J7Q7, A0A994J7R7, A0A994J7S1, A0A994J7S5, O95684

UniProt curated annotations — full annotation on UniProt →

Function. Required for anchoring microtubules to the centrosomes. Required for ciliation.

Subunit / interactions. Homodimer. Part of a ternary complex that contains CEP350, CEP43 and MAPRE1. Interacts directly with CEP350 and MAPRE1. Interacts with CEP19. Interacts (via N-terminus) with CEP350 (via C-terminus).

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

Tissue specificity. Ubiquitous. Highly expressed in heart, liver, muscle, kidney, intestine, colon, adrenal gland, prostate, testis, and pancreas.

Disease relevance. A chromosomal aberration involving CEP43 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins CEP43-FGFR1 or FGFR1-CEP43 may exhibit constitutive kinase activity and be responsible for the transforming activity.

Similarity. Belongs to the CEP43 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95684-1	1	yes
O95684-2	2, B
O95684-3	3

RefSeq proteins (3): NP_001265619, NP_008976, NP_919410 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006594	LisH	Conserved_site
IPR018993	FOP_dimerisation-dom_N	Domain

Pfam: PF09398

UniProt features (35 total): modified residue 10, compositionally biased region 6, helix 5, region of interest 3, splice variant 3, sequence variant 2, chain 1, domain 1, site 1, mutagenesis site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D68	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95684-F1	63.69	0.19

Functional residue map

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

Catalytic / active sites (1): 173–174 (breakpoint for translocation to form cep43-fgfr1 or fgfr1-cep43 fusion proteins)

Post-translational modifications (10): 143, 152, 156, 160, 170, 202, 234, 301, 326, 337

Mutagenesis-validated functional residues (1):

Position	Phenotype
74	abolishes homodimerization and leads to aggregation.

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants
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-5655302	Signaling by FGFR1 in disease
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-1226099	Signaling by FGFR in disease
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-1839124	FGFR1 mutant receptor activation
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-5663202	Diseases of signal transduction by growth factor receptors and second messengers
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: 207 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_MICROTUBULE_ANCHORING, GOBP_GROWTH, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, ACTGCAG_MIR173P, GOCC_MICROTUBULE_ORGANIZING_CENTER, GTGCCTT_MIR506, GOBP_POSITIVE_REGULATION_OF_CELL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOCC_CENTROSOME, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_NEGATIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP

GO Biological Process (6): negative regulation of protein kinase activity (GO:0006469), positive regulation of cell population proliferation (GO:0008284), cell projection organization (GO:0030030), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), microtubule anchoring (GO:0034453)

GO Molecular Function (4): protein kinase binding (GO:0019901), protein tyrosine kinase inhibitor activity (GO:0030292), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
FGFR1 mutant receptor activation	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Signaling by FGFR in disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Signaling by FGFR1 in disease	1
Organelle biogenesis and maintenance	1
Disease	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
positive regulation of cellular process	2
microtubule organizing center	2
intracellular membraneless organelle	2
cytoplasm	2
negative regulation of protein phosphorylation	1
protein kinase activity	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
cell population proliferation	1
regulation of cell population proliferation	1
cellular component organization	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
microtubule cytoskeleton organization	1
kinase binding	1
protein tyrosine kinase activity	1
protein kinase inhibitor activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
intracellular membrane-bounded organelle	1
centriole	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoskeleton	1

Protein interactions and networks

STRING

914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP43	RNASET2	O00584	886
CEP43	FGFR1	P11362	788
CEP43	FGFR1OP2	Q9NVK5	781
CEP43	CCR6	P51684	768
CEP43	CCRL2	O00421	759
CEP43	MYO18A	Q92614	756
CEP43	CEP350	Q5VT06	736
CEP43	CEP19	Q96LK0	730
CEP43	ZMYM2	Q9UBW7	616
CEP43	WRNIP1	Q96S55	581
CEP43	FOXP1	Q9H334	565
CEP43	TRIM24	O15164	558
CEP43	A0A3B3IT14	A0A3B3IT14	515
CEP43	ARL13B	Q3SXY8	501
CEP43	HLA-DQA2	P01906	480

IntAct

123 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
PPP2CA	STRN	psi-mi:“MI:0914”(association)	0.840
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
CEP43	CEP19	psi-mi:“MI:0915”(physical association)	0.770
CEP19	CEP43	psi-mi:“MI:0915”(physical association)	0.770
CEP350	CEP43	psi-mi:“MI:0914”(association)	0.770
CEP19	CEP43	psi-mi:“MI:0914”(association)	0.770
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
VASP	CEP43	psi-mi:“MI:0915”(physical association)	0.740
CEP43	VASP	psi-mi:“MI:0915”(physical association)	0.740
VASP	CEP43	psi-mi:“MI:0914”(association)	0.740
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
S100A6	CEP43	psi-mi:“MI:0407”(direct interaction)	0.540
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
CEP78	CEP43	psi-mi:“MI:0914”(association)	0.530
VASP	GTPBP1	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530
TADA2B	SUPT3H	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530

BioGRID (281): FGFR1OP (Two-hybrid), CEP19 (Two-hybrid), FGFR1OP (Affinity Capture-MS), CEP350 (Affinity Capture-MS), POTEI (Affinity Capture-MS), MSL3 (Affinity Capture-MS), PPP2R3C (Affinity Capture-MS), CEP19 (Affinity Capture-MS), FGFR1OP (Proximity Label-MS), FGFR1OP (Proximity Label-MS), FGFR1OP (Proximity Label-MS), FGFR1OP (Affinity Capture-Western), FGFR1OP (Affinity Capture-Western), FGFR1OP (Proximity Label-MS), FGFR1OP (Proximity Label-MS)

ESM2 similar proteins: A8MXK1, O09163, O46633, O54713, O76096, O95684, P01148, P01268, P01269, P01270, P01344, P04089, P07352, P07456, P07490, P10286, P10764, P13562, P14745, P15696, P17647, P23695, P33717, P37042, P41694, P49921, P51459, P51462, P52212, P55247, Q05078, Q08279, Q27IM2, Q28588, Q29423, Q2YDD1, Q3SXP7, Q4R7M4, Q4R7V3, Q5GAN6

Diamond homologs: O95684, P0CAX8, Q2YDD1, Q4R7V3, Q4V7C1, Q5ZJ24, Q66JX5, Q96NB1, Q9CZS3, Q9FQ24, Q9FQ25, B2RWW0, Q8N103, Q4V7R8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CEP43	“form complex”	FGFR1OP/CEP350	binding
CEP43	up-regulates	MAPRE1	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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
Signaling by GSK3beta mutants	5	52.1×	9e-07
CTNNB1 S33 mutants aren’t phosphorylated	5	52.1×	9e-07
CTNNB1 S37 mutants aren’t phosphorylated	5	52.1×	9e-07
CTNNB1 S45 mutants aren’t phosphorylated	5	52.1×	9e-07
CTNNB1 T41 mutants aren’t phosphorylated	5	52.1×	9e-07
Beta-catenin phosphorylation cascade	5	46.0×	1e-06
DARPP-32 events	5	32.6×	9e-06
Disassembly of the destruction complex and recruitment of AXIN to the membrane	6	29.3×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	7	45.8×	4e-08
protein localization to centrosome	6	36.1×	3e-06
non-motile cilium assembly	7	18.2×	2e-05
centrosome cycle	5	15.1×	2e-03
cilium assembly	15	9.9×	2e-08
intracellular protein localization	7	6.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	68
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2424749	NC_000006.11:g.(?167343076)(167453466_?)del	Pathogenic

SpliceAI

2744 predictions. Top by Δscore:

Variant	Effect	Δscore
6:166999512:AAGGT:A	donor_loss	1.0000
6:166999513:AGGT:A	donor_loss	1.0000
6:166999515:G:GA	donor_loss	1.0000
6:166999515:G:GG	donor_gain	1.0000
6:166999516:T:A	donor_loss	1.0000
6:167003244:GACG:G	donor_gain	1.0000
6:167003246:CGGTA:C	donor_loss	1.0000
6:167003248:GTAAG:G	donor_loss	1.0000
6:167003249:T:A	donor_loss	1.0000
6:167003807:GCACA:G	donor_gain	1.0000
6:167003812:G:GG	donor_gain	1.0000
6:167004262:A:AG	acceptor_gain	1.0000
6:167004263:G:GG	acceptor_gain	1.0000
6:167004397:GGGAA:G	donor_gain	1.0000
6:167004398:GGAA:G	donor_gain	1.0000
6:167004398:GGAAG:G	donor_gain	1.0000
6:167004399:GAA:G	donor_gain	1.0000
6:167004399:GAAG:G	donor_gain	1.0000
6:167004400:AAGTA:A	donor_loss	1.0000
6:167004401:AGTA:A	donor_loss	1.0000
6:167004402:G:GG	donor_gain	1.0000
6:167004402:GT:G	donor_loss	1.0000
6:167004403:TAA:T	donor_loss	1.0000
6:167022632:GTTT:G	donor_gain	1.0000
6:167024891:GAGA:G	donor_gain	1.0000
6:167024893:GA:G	donor_gain	1.0000
6:167024895:G:GG	donor_gain	1.0000
6:167032644:T:A	donor_loss	1.0000
6:167033866:T:A	acceptor_gain	1.0000
6:167033871:TTA:T	acceptor_loss	1.0000

AlphaMissense

2616 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:167000067:T:C	L37P	1.000
6:167003789:T:A	V93D	1.000
6:166999468:T:C	L19P	0.999
6:166999483:T:C	L24P	0.999
6:167000060:G:C	A35P	0.999
6:167000067:T:A	L37H	0.999
6:167000072:G:C	A39P	0.999
6:167000075:G:C	A40P	0.999
6:167000081:T:C	F42L	0.999
6:167000083:T:A	F42L	0.999
6:167000083:T:G	F42L	0.999
6:167003723:G:A	G71D	0.999
6:167003741:T:C	L77P	0.999
6:167003756:T:C	L82P	0.999
6:167003771:T:C	L87P	0.999
6:167000079:T:A	V41E	0.998
6:167000082:T:C	F42S	0.998
6:167000091:T:C	L45P	0.998
6:166999459:T:C	L16P	0.997
6:166999471:T:C	L20P	0.997
6:167000070:G:C	R38P	0.997
6:167003247:G:C	G71R	0.997
6:167003744:T:A	V78D	0.997
6:166999483:T:A	L24Q	0.996
6:166999501:T:C	L30P	0.996
6:166999510:T:C	I33T	0.996
6:166999514:G:C	K34N	0.996
6:166999514:G:T	K34N	0.996
6:167000061:C:A	A35D	0.996
6:167000082:T:G	F42C	0.996

dbSNP variants (sampled 300 via entrez): RS1000032773 (6:167037680 A>G,T), RS1000046212 (6:166999493 C>A,T), RS1000111003 (6:167010766 G>A), RS1000210776 (6:167028500 G>A), RS1000221327 (6:167020714 G>A), RS1000276060 (6:167036627 G>A), RS1000315787 (6:167052770 T>C), RS1000346753 (6:167008198 G>C,T), RS1000506678 (6:167016137 T>G), RS1000522018 (6:167046320 AAGGG>A,AAGGGAGGG), RS1000536115 (6:167053101 G>A,T), RS1000550530 (6:167022054 G>A,C), RS1000577193 (6:167014753 T>C), RS1000603130 (6:167021643 C>T), RS1000807247 (6:167013326 G>A,T)

Disease associations

OMIM: gene MIM:605392 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000692_2	Vitiligo	1.000000e-16
GCST001200_9	Graves’ disease	7.000000e-10
GCST002094_6	Crohn’s disease	8.000000e-12
GCST004131_51	Inflammatory bowel disease	9.000000e-15
GCST004132_22	Crohn’s disease	2.000000e-20
GCST004691_14	Huntington’s disease progression	6.000000e-06
GCST004748_52	Lung cancer	9.000000e-06
GCST004785_22	Vitiligo	2.000000e-18
GCST005524_5	Autoimmune thyroid diseases (Graves disease or Hashimoto’s thyroiditis)	2.000000e-07
GCST005526_5	Graves’ disease	3.000000e-07
GCST005537_203	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	9.000000e-25
GCST005537_205	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	8.000000e-07
GCST90013410_2	Basal cell carcinoma	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523602 (CHIMERIC PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
SU 5402	decreases activity	1
2-palmitoylglycerol	increases expression	1
CP 31398	increases expression	1
ICG 001	increases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Methylnitronitrosoguanidine	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	increases expression	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4359482	Binding	Inhibition of FGFR1OP/RET isoform 9 (unknown origin) expressed in mouse NIH/3T3 cells assessed as reduction in RET phosphorylation at Y905 residue at 1 to 100 nM measured after 2 hrs by Western blot analysis	Bioisosteric Discovery of NPA101.3, a Second-Generation RET/VEGFR2 Inhibitor Optimized for Single-Agent Polypharmacology. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
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
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