AOPEP

Summary

AOPEP (aminopeptidase O (putative), HGNC:1361) is a protein-coding gene on chromosome 9q22.32, encoding Aminopeptidase O (Q8N6M6). Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.

This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 84909 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 1,141 total — 62 pathogenic, 59 likely-pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• MANE Select transcript: NM_001193329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1361
Approved symbol	AOPEP
Name	aminopeptidase O (putative)
Location	9q22.32
Locus type	gene with protein product
Status	Approved
Aliases	C90RF3, FLJ14675, APO, AP-O
Ensembl gene	ENSG00000148120
Ensembl biotype	protein_coding
OMIM	619600
Entrez	84909

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 15 protein_coding, 10 protein_coding_CDS_not_defined, 6 retained_intron

ENST00000277198, ENST00000297979, ENST00000375315, ENST00000427193, ENST00000445181, ENST00000451893, ENST00000460573, ENST00000462125, ENST00000463372, ENST00000468164, ENST00000471978, ENST00000473778, ENST00000478473, ENST00000478603, ENST00000479161, ENST00000482056, ENST00000488186, ENST00000489318, ENST00000489562, ENST00000496567, ENST00000710812, ENST00000939091, ENST00000939092, ENST00000939093, ENST00000939094, ENST00000939095, ENST00000939096, ENST00000951986, ENST00000951987, ENST00000951988, ENST00000951989

RefSeq mRNA: 17 — MANE Select: NM_001193329 NM_001193329, NM_001193331, NM_001386061, NM_001386062, NM_001386063, NM_001386066, NM_001386067, NM_001386068, NM_001386069, NM_001386070, NM_001386071, NM_001386072, NM_001386073, NM_001386074, NM_001386075, NM_001386076, NM_032823

CCDS: CCDS55327, CCDS55328, CCDS6713

Canonical transcript exons

ENST00000375315 — 17 exons

Exon	Start	End
ENSE00001335355	94759649	94760580
ENSE00001642012	95086682	95087159
ENSE00001721386	94792765	94792918
ENSE00001769595	94773002	94773168
ENSE00003460915	94923986	94924175
ENSE00003493238	94979367	94979427
ENSE00003542214	95060694	95060810
ENSE00003560625	94928425	94928531
ENSE00003587084	95005542	95005616
ENSE00003594461	94967758	94967801
ENSE00003623570	95082575	95082719
ENSE00003643033	94800757	94801002
ENSE00003656559	94955908	94956015
ENSE00003662119	95005158	95005220
ENSE00003676980	95080694	95080780
ENSE00003692499	94955177	94955279
ENSE00003908993	94726699	94726751

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.6397 / max 467.3829, expressed in 1782 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97482	16.8037	1465
97464	7.7367	1695
97480	3.2714	1180
97483	2.3004	862
97485	1.9460	669
97490	1.0611	417
97470	0.8715	464
97486	0.5062	284
97466	0.3761	166
97481	0.3751	217

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.82	gold quality
right coronary artery	UBERON:0001625	98.71	gold quality
ascending aorta	UBERON:0001496	98.62	gold quality
thoracic aorta	UBERON:0001515	98.62	gold quality
descending thoracic aorta	UBERON:0002345	98.51	gold quality
body of uterus	UBERON:0009853	98.42	gold quality
lower esophagus	UBERON:0013473	98.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.36	gold quality
popliteal artery	UBERON:0002250	98.27	gold quality
tibial artery	UBERON:0007610	98.27	gold quality
aorta	UBERON:0000947	98.25	gold quality
lower esophagus mucosa	UBERON:0035834	98.21	gold quality
left uterine tube	UBERON:0001303	98.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.11	gold quality
sural nerve	UBERON:0015488	98.08	gold quality
left coronary artery	UBERON:0001626	97.75	gold quality
right lobe of liver	UBERON:0001114	97.67	gold quality
body of pancreas	UBERON:0001150	97.65	gold quality
artery	UBERON:0001637	97.63	gold quality
smooth muscle tissue	UBERON:0001135	97.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.55	gold quality
right atrium auricular region	UBERON:0006631	97.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.47	gold quality
esophagus	UBERON:0001043	97.39	gold quality
esophagus mucosa	UBERON:0002469	96.80	gold quality
skin of abdomen	UBERON:0001416	96.75	gold quality
metanephros cortex	UBERON:0010533	96.66	gold quality
tibial nerve	UBERON:0001323	96.56	gold quality
calcaneal tendon	UBERON:0003701	96.53	gold quality
endocervix	UBERON:0000458	96.43	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	20.16
E-HCAD-1	yes	18.88
E-HCAD-11	yes	9.25
E-MTAB-10290	no	175.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting AOPEP, 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-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4291	99.20	68.88	2969

Literature-anchored findings (GeneRIF, showing 6)

• HPV-16 E6 was confirmed to regulate microRNA miR-23b indirectly through the DNA methylation of host gene C9orf3 and thus induce c-MET and inhibit apoptosis in cervical cancer cells. (PMID:28077801)
• An association study of C9orf3, a novel component of the renin-angiotensin system, and hypertension in diabetes. (PMID:32999396)
• Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement. (PMID:34596301)
• Suicide Related Phenotypes in a Bipolar Sample: Genetic Underpinnings. (PMID:34680877)
• AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism. (PMID:35306330)
• Mutation screening of AOPEP variants in a large dystonia cohort. (PMID:36933031)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
mus_musculus	Aopep	ENSMUSG00000021458
rattus_norvegicus	Aopep	ENSRNOG00000017505
drosophila_melanogaster	CG7653	FBGN0028935
drosophila_melanogaster	CG9806	FBGN0030222
drosophila_melanogaster	CG2111	FBGN0030223
drosophila_melanogaster	CG6071	FBGN0036186
drosophila_melanogaster	CG5849	FBGN0038897
drosophila_melanogaster	CG3502	FBGN0046253
drosophila_melanogaster	CG31233	FBGN0051233
drosophila_melanogaster	CG31343	FBGN0051343
drosophila_melanogaster	CG31445	FBGN0051445
drosophila_melanogaster	SP1029	FBGN0263236
drosophila_melanogaster	CG46339	FBGN0285963
caenorhabditis_elegans	F49B2.6	WBGENE00009865
caenorhabditis_elegans		WBGENE00011587
caenorhabditis_elegans		WBGENE00012776

Paralogs (11): TRHDE (ENSG00000072657), LTA4H (ENSG00000111144), LNPEP (ENSG00000113441), ENPEP (ENSG00000138792), NPEPPS (ENSG00000141279), RNPEPL1 (ENSG00000142327), ERAP1 (ENSG00000164307), ERAP2 (ENSG00000164308), ANPEP (ENSG00000166825), LVRN (ENSG00000172901), RNPEP (ENSG00000176393)

Protein

Protein identifiers

Aminopeptidase O — Q8N6M6 (reviewed: Q8N6M6)

All UniProt accessions (3): Q8N6M6, H0Y7A8, X6RBX4

UniProt curated annotations — full annotation on UniProt →

Function. Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.

Subcellular location. Nucleus. Nucleolus Cytoplasm.

Disease relevance. Dystonia 31 (DYT31) [MIM:619565] A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT31 is an autosomal recessive, progressive form with onset from childhood to young adulthood. Involuntary muscle twisting movements and postural abnormalities affect the upper and lower limbs, neck, face, and trunk. Some patients may have orofacial dyskinesia resulting in articulation and swallowing difficulties. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8N6M6-1	1	yes
Q8N6M6-2	2
Q8N6M6-3	3
Q8N6M6-4	4

RefSeq proteins (17): NP_001180258, NP_001180260, NP_001372990, NP_001372991, NP_001372992, NP_001372995, NP_001372996, NP_001372997, NP_001372998, NP_001372999, NP_001373000, NP_001373001, NP_001373002, NP_001373003, NP_001373004, NP_001373005, NP_116212 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014782	Peptidase_M1_dom	Domain
IPR015211	Peptidase_M1_C	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR033577	AOPep	Family
IPR038502	M1_LTA-4_hydro/amino_C_sf	Homologous_superfamily
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily

Pfam: PF01433, PF09127

UniProt features (19 total): sequence variant 7, splice variant 5, binding site 3, chain 1, short sequence motif 1, active site 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6M6-F1	83.36	0.66

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 (2): 480 (proton acceptor); 586 (transition state stabilizer)

Ligand- & substrate-binding residues (3): 479; 483; 502

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 223 (showing top): KOBAYASHI_EGFR_SIGNALING_24HR_UP, WANG_CLIM2_TARGETS_UP, TSENG_IRS1_TARGETS_UP, TGCGCANK_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOMF_METALLOPEPTIDASE_ACTIVITY, JAEGER_METASTASIS_DN, GOZGIT_ESR1_TARGETS_DN, STARK_HYPPOCAMPUS_22Q11_DELETION_UP, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, ROZANOV_MMP14_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, chr9q22, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (7): zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), aminopeptidase activity (GO:0004177), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleolus (GO:0005730), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
exopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AOPEP	DENND1A	Q8TEH3	737
AOPEP	TOX3	O15405	642
AOPEP	SUOX	P51687	621
AOPEP	SYNPO2L	Q9H987	608
AOPEP	RAB5B	P35239	595
AOPEP	KRR1	Q13601	571
AOPEP	LHCGR	P22888	544
AOPEP	FSHR	P23945	543
AOPEP	SYNE2	Q8WXH0	512
AOPEP	ZFHX3	Q15911	507
AOPEP	NEIL2	Q969S2	504
AOPEP	FBN3	Q75N90	499
AOPEP	INSR	P06213	486
AOPEP	PRRX1	P54821	483
AOPEP	ERICH6B	Q5W0A0	476

IntAct

13 interactions, top by confidence:

A	B	Type	Score
AOPEP	TOMM70	psi-mi:“MI:0915”(physical association)	0.400
AOPEP	H1-2	psi-mi:“MI:0915”(physical association)	0.400
BMPR1A	AOPEP	psi-mi:“MI:0915”(physical association)	0.370
AOPEP	BUB1	psi-mi:“MI:0915”(physical association)	0.370
CDH1	AOPEP	psi-mi:“MI:0915”(physical association)	0.370
AOPEP	CDKN2A	psi-mi:“MI:0915”(physical association)	0.370
AOPEP	DLC1	psi-mi:“MI:0915”(physical association)	0.370
AOPEP	EGFR	psi-mi:“MI:0915”(physical association)	0.370
AOPEP	MLH3	psi-mi:“MI:0915”(physical association)	0.370
NRAS	AOPEP	psi-mi:“MI:0915”(physical association)	0.370
SMAD4	AOPEP	psi-mi:“MI:0915”(physical association)	0.370
AOPEP	ZBTB39	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): LRRC40 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), SUZ12 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), C9orf3 (Affinity Capture-RNA), C9orf3 (Proximity Label-MS), C9orf3 (Proximity Label-MS), C9orf3 (Two-hybrid), C9orf3 (Two-hybrid), C9orf3 (Two-hybrid), C9orf3 (Two-hybrid), C9orf3 (Two-hybrid), C9orf3 (Two-hybrid), C9orf3 (Two-hybrid)

ESM2 similar proteins: A2CI35, D3YWQ0, D3ZKV9, F1MAB7, F4HX15, O08653, O54705, O61309, O62699, O75164, O75912, P29477, P35228, P69527, P79290, P97499, Q06518, Q09178, Q20CR4, Q26240, Q27995, Q28314, Q3MHJ7, Q3TGW2, Q4G017, Q4VSN2, Q4VSN3, Q4VSN4, Q4VSN5, Q5R667, Q5RD88, Q5TEA3, Q5XI74, Q67E00, Q67E01, Q6IND4, Q6P5D3, Q6P996, Q6TEQ0, Q6XUX3

Diamond homologs: P69527, Q8BXQ6, Q8N6M6, P91887

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1141 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	62
Likely pathogenic	59
Uncertain significance	500
Likely benign	365
Benign	18

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069415	NM_000136.3(FANCC):c.1199del (p.Phe400fs)	Pathogenic
1072020	NM_000136.3(FANCC):c.1327_1328del (p.Met443fs)	Pathogenic
1075774	NM_000136.3(FANCC):c.1630_1631insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAGATCGAGACCATCCCGGCTANNNNNNNNNNAAAAAAAAAAGAAAGCCCTAGATCAG (p.Ser543_Glu544insGlyArgAlaArgTrpLeuThrProValIleProAlaLeuTrpGluAlaGluAlaGlyGlySerArgGlyGlnGluIleGluThrIleProAlaXaaXaaXaaXaaLysLysLysGluSerProArgSer)	Pathogenic
1075818	NM_000136.3(FANCC):c.1181G>A (p.Trp394Ter)	Pathogenic
1192126	NM_000136.3(FANCC):c.839C>A (p.Ser280Ter)	Pathogenic
12050	NM_000136.3(FANCC):c.1487T>G (p.Leu496Arg)	Pathogenic
1319959	NM_001193329.3(AOPEP):c.1477C>T (p.Arg493Ter)	Pathogenic
1319960	NM_001193329.3(AOPEP):c.777G>A (p.Trp259Ter)	Pathogenic
1319963	NM_001193329.3(AOPEP):c.1744del (p.Met582fs)	Pathogenic
1322874	NM_000136.3(FANCC):c.1002del (p.Phe335fs)	Pathogenic
1421752	NM_000136.3(FANCC):c.635del (p.Gln212fs)	Pathogenic
1442299	NM_000136.3(FANCC):c.574dup (p.Thr192fs)	Pathogenic
1452013	NM_000136.3(FANCC):c.957_958delinsTT (p.Gln320Ter)	Pathogenic
1453776	NM_000136.3(FANCC):c.916_917del (p.Asp306fs)	Pathogenic
1457045	NM_000136.3(FANCC):c.723C>A (p.Cys241Ter)	Pathogenic
1685808	NM_000136.3(FANCC):c.1653dup (p.Lys552Ter)	Pathogenic
1740188	NM_000136.3(FANCC):c.1173dup (p.Glu392Ter)	Pathogenic
1753699	NM_000136.3(FANCC):c.646C>T (p.Gln216Ter)	Pathogenic
1767341	NM_000136.3(FANCC):c.954del (p.Phe318fs)	Pathogenic
1946496	NM_000136.3(FANCC):c.1655_1658dup (p.Leu554fs)	Pathogenic
2031217	NM_000136.3(FANCC):c.1060C>T (p.Gln354Ter)	Pathogenic
2074990	NM_000136.3(FANCC):c.532G>T (p.Glu178Ter)	Pathogenic
2100211	NM_000136.3(FANCC):c.1106del (p.Lys369fs)	Pathogenic
2105158	NM_000136.3(FANCC):c.1351_1352del (p.Gly451fs)	Pathogenic
2560853	NM_000136.3(FANCC):c.1233dup (p.Leu412fs)	Pathogenic
2663844	NM_001193329.3(AOPEP):c.964+2T>G	Pathogenic
2763653	NM_000136.3(FANCC):c.1285_1297del (p.Tyr429fs)	Pathogenic
2772495	NM_000136.3(FANCC):c.1209G>A (p.Trp403Ter)	Pathogenic
2802472	NM_000136.3(FANCC):c.1563dup (p.Ile522fs)	Pathogenic
2809579	NM_000136.3(FANCC):c.1551_1552del (p.Glu517fs)	Pathogenic

SpliceAI

8663 predictions. Top by Δscore:

Variant	Effect	Δscore
9:94766898:A:AG	donor_gain	1.0000
9:94773166:A:T	donor_gain	1.0000
9:94813963:G:GT	donor_gain	1.0000
9:94953439:C:G	donor_gain	1.0000
9:95005156:A:AG	acceptor_gain	1.0000
9:95005157:G:GG	acceptor_gain	1.0000
9:95060692:A:AG	acceptor_gain	1.0000
9:95060693:G:GG	acceptor_gain	1.0000
9:95060693:GCTT:G	acceptor_gain	1.0000
9:95080688:CTCCA:C	acceptor_loss	1.0000
9:95080689:TCCAG:T	acceptor_loss	1.0000
9:95080690:CCAGG:C	acceptor_loss	1.0000
9:95080691:CAGG:C	acceptor_loss	1.0000
9:95080692:A:AG	acceptor_gain	1.0000
9:95080692:A:C	acceptor_loss	1.0000
9:95080692:AG:A	acceptor_gain	1.0000
9:95080693:G:GT	acceptor_gain	1.0000
9:95080693:GG:G	acceptor_gain	1.0000
9:95080693:GGTTC:G	acceptor_gain	1.0000
9:95080777:TCAGG:T	donor_loss	1.0000
9:95080778:CAGG:C	donor_loss	1.0000
9:95080780:GGT:G	donor_loss	1.0000
9:95080781:G:GG	donor_gain	1.0000
9:95080781:GTAG:G	donor_loss	1.0000
9:95080782:T:G	donor_loss	1.0000
9:94766942:G:GT	donor_gain	0.9900
9:94773165:GAAGG:G	donor_loss	0.9900
9:94773166:AAG:A	donor_loss	0.9900
9:94773167:AGGT:A	donor_loss	0.9900
9:94773168:GGTAC:G	donor_loss	0.9900

AlphaMissense

5413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:94773129:A:C	S309R	0.998
9:94773131:T:A	S309R	0.998
9:94773131:T:G	S309R	0.998
9:94924104:T:A	W495R	0.998
9:94924104:T:C	W495R	0.998
9:94924116:T:A	W499R	0.998
9:94924116:T:C	W499R	0.998
9:94773084:T:A	W294R	0.997
9:94773084:T:C	W294R	0.997
9:94924074:T:A	W485R	0.997
9:94924074:T:C	W485R	0.997
9:94773090:G:C	A296P	0.994
9:94924106:G:C	W495C	0.994
9:94924106:G:T	W495C	0.994
9:94924122:A:C	S501R	0.994
9:94924124:T:A	S501R	0.994
9:94924124:T:G	S501R	0.994
9:94773010:T:A	V269D	0.993
9:94773038:C:A	N278K	0.993
9:94773038:C:G	N278K	0.993
9:94792836:T:A	W346R	0.993
9:94792836:T:C	W346R	0.993
9:94773041:G:C	R279S	0.992
9:94773041:G:T	R279S	0.992
9:94773097:T:A	V298D	0.992
9:94924118:G:C	W499C	0.992
9:94924118:G:T	W499C	0.992
9:94979401:T:A	W651R	0.992
9:94979401:T:C	W651R	0.992
9:94924128:G:C	G503R	0.990

dbSNP variants (sampled 300 via entrez): RS1000008846 (9:95081895 C>A,T), RS1000016416 (9:94726555 C>A,G,T), RS1000025682 (9:95129239 A>G), RS1000027841 (9:94861218 A>G), RS1000030031 (9:95057223 C>G,T), RS1000031140 (9:94907417 C>G), RS1000037776 (9:95114474 G>A), RS1000054971 (9:94854993 C>A), RS1000061994 (9:95099869 A>G), RS1000062359 (9:94979860 C>T), RS1000077968 (9:94998625 G>A,C), RS1000086369 (9:94725046 G>A), RS1000098667 (9:95108765 C>T), RS1000101306 (9:94905872 G>A,C), RS1000106900 (9:94802044 T>C)

Disease associations

OMIM: gene MIM:619600 | disease phenotypes: MIM:227645, MIM:227650, MIM:619565, MIM:167000, MIM:109400, MIM:300888

GenCC curated gene-disease

Mondo (11): Fanconi anemia complementation group C (MONDO:0009213), hereditary neoplastic syndrome (MONDO:0015356), Fanconi anemia (MONDO:0019391), breast cancer (MONDO:0007254), hereditary breast ovarian cancer syndrome (MONDO:0003582), Fanconi anemia complementation group A (MONDO:0009215), dystonia 31 (MONDO:0030455), ovarian cancer (MONDO:0008170), familial ovarian cancer (MONDO:0016248), nevoid basal cell carcinoma syndrome (MONDO:0007187), X-linked central congenital hypothyroidism with late-onset testicular enlargement (MONDO:0010475)

Orphanet (7): Inherited cancer-predisposing syndrome (Orphanet:140162), Fanconi anemia (Orphanet:84), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Rare ovarian cancer (Orphanet:213500), Gorlin syndrome (Orphanet:377), X-linked central congenital hypothyroidism with late-onset testicular enlargement (Orphanet:329235), OBSOLETE: Familial ovarian cancer (Orphanet:213517)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000716	Depression
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001621	Weak voice
HP:0002015	Dysphagia
HP:0002356	Writer’s cramp
HP:0002533	Abnormal posturing
HP:0003552	Muscle stiffness
HP:0003621	Juvenile onset
HP:0007325	Generalized dystonia
HP:0011462	Young adult onset
HP:0012179	Craniofacial dystonia
HP:0031959	Leg dystonia
HP:0031960	Arm dystonia

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000824_5	Erectile dysfunction and prostate cancer treatment	4.000000e-06
GCST001499_7	Atrial fibrillation	4.000000e-11
GCST001634_5	Polycystic ovary syndrome	5.000000e-14
GCST001762_812	Obesity-related traits	4.000000e-06
GCST003255_3	Urinary albumin-to-creatinine ratio	5.000000e-06
GCST004296_6	Atrial fibrillation	2.000000e-06
GCST004297_15	Atrial fibrillation	3.000000e-11
GCST005273_4	Polycystic ovary syndrome	5.000000e-13
GCST006061_25	Atrial fibrillation	2.000000e-36
GCST006061_45	Atrial fibrillation	2.000000e-35
GCST006414_133	Atrial fibrillation	3.000000e-34
GCST007089_6	Polycystic ovary syndrome	3.000000e-08
GCST012335_23	Hodgkin’s lymphoma	3.000000e-11
GCST90000025_407	Appendicular lean mass	2.000000e-19
GCST90002403_611	Red blood cell count	1.000000e-09
GCST90020028_346	Hip circumference adjusted for BMI	2.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004980	appendicular lean mass
EFO:0004305	erythrocyte count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001478	Basal Cell Nevus Syndrome	C04.182.089.530.690.150; C04.557.470.200.165.150; C04.557.470.565.165.150; C04.700.175; C05.116.099.105; C05.500.470.690.150; C07.320.450.670.130; C16.131.077.130; C16.320.700.175
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831223 (PROTEIN FAMILY)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4647554	AOPEP, FANCC		0.00	0
rs1011784	AOPEP, MIR23B, MIR24-1, MIR27B, MIR3074		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M1: Aminopeptidase N

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects methylation	4
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	3
Valproic Acid	affects cotreatment, increases expression	3
sodium arsenite	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects methylation, affects cotreatment, increases methylation	1
sodium arsenate	decreases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
chromium hexavalent ion	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Dasatinib	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334276	ADMET	Stability in pH 2 HCl assessed as aminopeptidase (unknown origin)-mediated compound hydrolysis by measuring parent compound remaining at 200 uM up to 6 hrs by RP-HPLC analysis	Astratides: Insulin-Modulating, Insecticidal, and Antifungal Cysteine-Rich Peptides from Astragalus membranaceus. — J Nat Prod

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06519786	PHASE3	UNKNOWN	Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00001749	PHASE2	COMPLETED	Medical Treatment for Diamond Blackfan Anemia
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT00053989	PHASE2	COMPLETED	NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
NCT00084695	PHASE2	UNKNOWN	Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases
NCT00258427	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
NCT00453388	PHASE2	COMPLETED	Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
NCT01071239	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplant for Fanconi Anemia
NCT02143830	PHASE2	RECRUITING	HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
NCT02931071	PHASE2	COMPLETED	Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1
NCT03206086	PHASE2	ACTIVE_NOT_RECRUITING	Eltrombopag for People With Fanconi Anemia
NCT03398824	PHASE2	COMPLETED	Pilot Study of Metformin for Patients With Fanconi Anemia
NCT03476330	PHASE2	COMPLETED	Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT03600909	PHASE2	TERMINATED	A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT06045052	PHASE2	COMPLETED	Eltrombopag for Treatment of Fanconi Anemia
NCT00001399	PHASE1	COMPLETED	Gene Therapy for the Treatment of Fanconi’s Anemia Type C
NCT00005896	PHASE1	UNKNOWN	Phase I Pilot Study of CD34 Enriched, Fanconi’s Anemia Complementation Group C Gene Transduced Autologous Peripheral Blood Stem Cell Transplantation in Patients With Fanconi’s Anemia
NCT00006127	PHASE1	UNKNOWN	Phase I Study of Amifostine in Patients With Bone Marrow Failure Related to Fanconi’s Anemia
NCT00093743	PHASE1	COMPLETED	Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
NCT00243399	PHASE1	COMPLETED	Oxandrolone for the Treatment of Bone Marrow Aplasia in Fanconi Anemia
NCT00272857	PHASE1	COMPLETED	Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia
NCT00317876	PHASE1	COMPLETED	Cyclophosphamide in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Fanconi’s Anemia
NCT00586274	PHASE1	TERMINATED	Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT
NCT01331018	PHASE1	TERMINATED	Gene Therapy for Fanconi Anemia
NCT01720147	PHASE1	COMPLETED	Quercetin in Children With Fanconi Anemia; a Pilot Study
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1