AK3

Summary

AK3 (adenylate kinase 3, HGNC:17376) is a protein-coding gene on chromosome 9p24.1, encoding GTP:AMP phosphotransferase AK3, mitochondrial (Q9UIJ7). Mitochondrial adenylate kinase with a specific GTP:AMP phosphotransferase activity. It is a common-essential gene (DepMap: required in 94.5% of cancer cell lines).

The protein encoded by this gene is a GTP:ATP phosphotransferase that is found in the mitochondrial matrix. Several transcript variants encoding a few different isoforms have been found for this gene.

Source: NCBI Gene 50808 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 132 total — 63 pathogenic, 3 likely-pathogenic
• Cancer dependency (DepMap): dependent in 94.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_016282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17376
Approved symbol	AK3
Name	adenylate kinase 3
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	AKL3L1
Ensembl gene	ENSG00000147853
Ensembl biotype	protein_coding
OMIM	609290
Entrez	50808

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000359883, ENST00000381809, ENST00000447596, ENST00000611749, ENST00000867651

RefSeq mRNA: 5 — MANE Select: NM_016282 NM_001199852, NM_001199853, NM_001199855, NM_001199856, NM_016282

CCDS: CCDS56561, CCDS56562, CCDS6455

Canonical transcript exons

ENST00000381809 — 5 exons

Exon	Start	End
ENSE00001914265	4740937	4741202
ENSE00001929396	4709556	4713096
ENSE00003592196	4722506	4722625
ENSE00003697916	4719135	4719307
ENSE00003700648	4718419	4718537

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2047 / max 148.3770, expressed in 1786 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99808	43.8349	1822
99809	11.9384	1774
99810	1.8023	1076
99807	1.2452	846
99804	0.2188	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	99.73	gold quality
left ventricle myocardium	UBERON:0006566	99.64	gold quality
upper arm skin	UBERON:0004263	99.59	gold quality
kidney epithelium	UBERON:0004819	99.55	gold quality
deltoid	UBERON:0001476	99.47	gold quality
myocardium	UBERON:0002349	99.42	gold quality
tibialis anterior	UBERON:0001385	99.37	gold quality
ileal mucosa	UBERON:0000331	99.35	gold quality
jejunal mucosa	UBERON:0000399	99.30	gold quality
vastus lateralis	UBERON:0001379	99.23	gold quality
biceps brachii	UBERON:0001507	99.13	gold quality
jejunum	UBERON:0002115	99.09	gold quality
heart right ventricle	UBERON:0002080	99.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.01	gold quality
upper leg skin	UBERON:0004262	98.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.69	gold quality
skin of hip	UBERON:0001554	98.67	gold quality
colonic mucosa	UBERON:0000317	98.65	gold quality
caput epididymis	UBERON:0004358	98.51	gold quality
renal medulla	UBERON:0000362	98.47	gold quality
oral cavity	UBERON:0000167	98.43	gold quality
skeletal muscle tissue	UBERON:0001134	98.29	gold quality
esophagus squamous epithelium	UBERON:0006920	98.19	gold quality
adrenal tissue	UBERON:0018303	98.10	gold quality
quadriceps femoris	UBERON:0001377	98.09	gold quality
seminal vesicle	UBERON:0000998	97.93	gold quality
muscle tissue	UBERON:0002385	97.90	gold quality
mammalian vulva	UBERON:0000997	97.89	gold quality
body of tongue	UBERON:0011876	97.85	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.94
E-MTAB-2983	no	2112.17
E-CURD-135	no	1699.90
E-MTAB-7606	no	88.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

160 targeting AK3, 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-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to colorectal cancer (PMID:27888432)
• Adenylate Kinase Isozyme 3 Regulates Mitochondrial Energy Metabolism and Knockout Alters HeLa Cell Metabolism. (PMID:35457131)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ak3	ENSDARG00000058226
mus_musculus	Ak3	ENSMUSG00000024782
rattus_norvegicus	Ak3	ENSRNOG00000052506
drosophila_melanogaster	Ak3	FBGN0042094

Paralogs (9): AK2 (ENSG00000004455), AK1 (ENSG00000106992), AK7 (ENSG00000140057), AK5 (ENSG00000154027), AK9 (ENSG00000155085), CMPK1 (ENSG00000162368), AK4 (ENSG00000162433), AK8 (ENSG00000165695), AK4P3 (ENSG00000233381)

Protein

Protein identifiers

GTP:AMP phosphotransferase AK3, mitochondrial — Q9UIJ7 (reviewed: Q9UIJ7)

Alternative names: Adenylate kinase 3, Adenylate kinase 3 alpha-like 1, Adenylate kinase isozyme 3

All UniProt accessions (1): Q9UIJ7

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial adenylate kinase with a specific GTP:AMP phosphotransferase activity. Could also use ITP as phosphate donor. Its physiological function is to recycle GTP into GDP which is necessary for the TCA cycle in the mitochondrial matrix.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Highly expressed in heart, skeletal muscle and liver, moderately expressed in pancreas and kidney, and weakly expressed in placenta, brain and lung.

Activity regulation. Inhibited by ATP.

Domain organisation. Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP binding. Assembling and disassembling the active center during each catalytic cycle provides an effective means to prevent GTP hydrolysis.

Similarity. Belongs to the adenylate kinase family. AK3 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UIJ7-1	1	yes
Q9UIJ7-2	2
Q9UIJ7-3	3

RefSeq proteins (5): NP_001186781, NP_001186782, NP_001186784, NP_001186785, NP_057366* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000850	Adenylat/UMP-CMP_kin	Family
IPR006259	Adenyl_kin_sub	Family
IPR007862	Adenylate_kinase_lid-dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR028586	AK3/Ak4_mitochondrial	Family
IPR033690	Adenylat_kinase_CS	Conserved_site
IPR036193	ADK_active_lid_dom_sf	Homologous_superfamily

Pfam: PF00406, PF05191

Enzyme classification (BRENDA):

• EC 2.7.4.10 — nucleoside-triphosphate-adenylate kinase (BRENDA: 6 organisms, 49 substrates, 17 inhibitors, 13 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
AMP	0.033–0.21	3
GTP	0.056–0.359	3
ADP	0.29	1
ATP	1	1
CTP	9.1	1
GDP	0.0012	1
ITP	0.63	1
UTP	7.4	1

Catalyzed reactions (Rhea), 3 shown:

• a ribonucleoside 5’-triphosphate + AMP = a ribonucleoside 5’-diphosphate + ADP (RHEA:13749)
• GTP + AMP = GDP + ADP (RHEA:29863)
• ITP + AMP = IDP + ADP (RHEA:29867)

UniProt features (62 total): binding site 17, modified residue 13, helix 9, strand 7, turn 6, sequence conflict 5, region of interest 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1ZD8	X-RAY DIFFRACTION	1.48
6ZJE	X-RAY DIFFRACTION	1.48
6ZJD	X-RAY DIFFRACTION	1.75
6ZJB	X-RAY DIFFRACTION	1.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIJ7-F1	91.79	0.84

Functional residue map

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

Ligand- & substrate-binding residues (17): 64; 91; 94; 98; 128; 138; 139; 161; 172; 201; 17; 19 …

Post-translational modifications (13): 20, 34, 37, 57, 64, 64, 80, 80, 174, 174, 189, 189, 203

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis

MSigDB gene sets: 332 (showing top): RNGTGGGC_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RIBOSOME_BIOGENESIS, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, HARRIS_HYPOXIA, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, MODULE_308, USF_C, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (10): ADP biosynthetic process (GO:0006172), blood coagulation (GO:0007596), nucleoside triphosphate biosynthetic process (GO:0009142), AMP metabolic process (GO:0046033), GTP metabolic process (GO:0046039), ITP metabolic process (GO:0046041), UTP metabolic process (GO:0046051), nucleobase-containing compound metabolic process (GO:0006139), nucleotide metabolic process (GO:0009117), nucleoside monophosphate metabolic process (GO:0009123)

GO Molecular Function (11): ATP binding (GO:0005524), GTP binding (GO:0005525), ligase activity (GO:0016874), nucleoside triphosphate adenylate kinase activity (GO:0046899), nucleotide binding (GO:0000166), AMP kinase activity (GO:0004017), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, phosphate group as acceptor (GO:0016776), nucleobase-containing compound kinase activity (GO:0019205)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleotide metabolic process	3
purine ribonucleoside triphosphate metabolic process	2
nucleoside phosphate metabolic process	2
purine ribonucleoside triphosphate binding	2
catalytic activity	2
transferase activity, transferring phosphorus-containing groups	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside diphosphate biosynthetic process	1
ADP metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
nucleoside triphosphate metabolic process	1
nucleoside phosphate biosynthetic process	1
purine ribonucleoside monophosphate metabolic process	1
pyrimidine ribonucleoside triphosphate metabolic process	1
pyrimidine ribonucleotide metabolic process	1
primary metabolic process	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1
phosphotransferase activity, phosphate group as acceptor	1
nucleobase-containing compound kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleoside monophosphate kinase activity	1
binding	1
kinase activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3163 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AK3	NME4	O00746	787
AK3	DGUOK	P78532	725
AK3	AK7	Q96M32	692
AK3	NT5M	Q9NPB1	685
AK3	EVI2B	P34910	647
AK3	CMPK2	Q5EBM0	605
AK3	EVI2A	P22794	602
AK3	DTYMK	P23919	561
AK3	TK2	O00142	547
AK3	RNF145	Q96MT1	520
AK3	OMG	P23515	497
AK3	AK5	Q9Y6K8	483
AK3	PGM2	Q96G03	481
AK3	RCL1	Q9Y2P8	466
AK3	GUK1	Q16774	447

IntAct

63 interactions, top by confidence:

A	B	Type	Score
AK3	APPBP2	psi-mi:“MI:0915”(physical association)	0.720
APPBP2	AK3	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
KRTAP10-8	AK3	psi-mi:“MI:0915”(physical association)	0.560
FBLN1	AK3	psi-mi:“MI:0915”(physical association)	0.560
AK3	APOE	psi-mi:“MI:0915”(physical association)	0.560
BDNF	AK3	psi-mi:“MI:0915”(physical association)	0.560
GAPDH	AK3	psi-mi:“MI:0915”(physical association)	0.560
GRN	AK3	psi-mi:“MI:0915”(physical association)	0.560
AK3	WFS1	psi-mi:“MI:0915”(physical association)	0.560
AK3	JPH3	psi-mi:“MI:0915”(physical association)	0.560
HTT	AK3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (80): AK3 (Two-hybrid), AK3 (Two-hybrid), IBA57 (Affinity Capture-MS), HNRNPUL2 (Co-fractionation), RPS14 (Co-fractionation), AK3 (Affinity Capture-MS), AK3 (Proximity Label-MS), AK3 (Proximity Label-MS), AK3 (Proximity Label-MS), AK3 (Proximity Label-MS), AK3 (Affinity Capture-MS), AK3 (Co-fractionation), AK3 (Co-fractionation), AK3 (Co-fractionation), AK3 (Co-fractionation)

ESM2 similar proteins: A1L1L6, A5PJA1, B9N1F9, B9SQI7, E0CSI1, O43929, O80526, O95045, P08760, P29411, Q05B63, Q28DS0, Q28I42, Q2HJF8, Q2QNG7, Q2QZ86, Q2R483, Q2YDI2, Q5BJZ6, Q5EB68, Q5M939, Q5R4J9, Q5R6Z7, Q5RDZ0, Q5ZID6, Q5ZKF6, Q5ZM73, Q6AY91, Q6N069, Q6NVC5, Q7SYN4, Q7Z4G4, Q80UM3, Q8GYA6, Q8IXI2, Q8JGT5, Q8RWF0, Q8VCP8, Q91W63, Q923S8

Diamond homologs: A0K9X1, A1V117, A2S516, A3MN48, A3N6K4, A3NS87, A4JH80, A6T5N7, A7ZIN4, A7ZXD2, A8GAV3, A9AGK1, A9KED8, A9NBU5, B1IZC0, B1JXF8, B1LJN2, B1XFR1, B1YVE0, B2U4S7, B2VHX2, B3MCQ5, B4E9G1, B4I2A8, B4KLY1, B4MQT3, B4PAR6, B4QBH8, B4SWY1, B4T9I1, B4TMG6, B5BD44, B5EXN0, B5FLJ7, B5QU77, B5R612, B5XCA1, B5Y0N3, B5YHP1, B6I0C6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	3
Uncertain significance	57
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
144246	GRCh38/hg38 9p24.3-23(chr9:204193-10164955)x1	Pathogenic
144441	GRCh38/hg38 9p24.3-23(chr9:204193-11277770)x1	Pathogenic
144686	GRCh38/hg38 9p24.3-23(chr9:204090-13146846)x1	Pathogenic
146111	GRCh38/hg38 9p24.3-24.1(chr9:220253-8866675)x1	Pathogenic
146231	GRCh38/hg38 9p24.3-24.1(chr9:204193-6968724)x1	Pathogenic
146254	GRCh38/hg38 9p24.3-23(chr9:204193-10852686)x1	Pathogenic
146684	GRCh38/hg38 9p24.3-23(chr9:204104-11298187)x1	Pathogenic
146719	GRCh38/hg38 9p24.3-22.2(chr9:204193-16897580)x1	Pathogenic
147561	GRCh38/hg38 9p24.2-23(chr9:3591159-9361786)x3	Pathogenic
147623	GRCh38/hg38 9p24.2-24.1(chr9:4152060-8518353)x1	Pathogenic
147703	GRCh38/hg38 9p24.3-22.3(chr9:214367-16307944)x1	Pathogenic
148264	GRCh38/hg38 9p24.3-24.1(chr9:204104-5426099)x3	Pathogenic
148301	GRCh38/hg38 9p24.3-24.1(chr9:204104-5695507)x1	Pathogenic
148381	GRCh38/hg38 9p24.3-24.1(chr9:204104-8266492)x1	Pathogenic
148598	GRCh38/hg38 9p24.3-23(chr9:204104-14182668)x1	Pathogenic
148677	GRCh38/hg38 9p24.3-24.1(chr9:204104-7133443)x1	Pathogenic
149059	GRCh38/hg38 9p24.3-24.1(chr9:204104-5657733)x1	Pathogenic
149060	GRCh38/hg38 9p24.3-23(chr9:204104-10023901)x1	Pathogenic
150751	GRCh38/hg38 9p24.3-23(chr9:204090-9282864)x1	Pathogenic
151916	GRCh38/hg38 9p24.3-24.1(chr9:211086-7444397)x1	Pathogenic
1527476	GRCh37/hg19 9p24.3-24.1(chr9:203861-5909152)	Pathogenic
1527477	GRCh37/hg19 9p24.3-24.1(chr9:203861-7759331)	Pathogenic
1527479	GRCh37/hg19 9p24.3-23(chr9:203861-9631665)	Pathogenic
1527480	GRCh37/hg19 9p24.3-23(chr9:203861-11414732)	Pathogenic
1527484	GRCh37/hg19 9p24.3-22.3(chr9:203861-15211277)	Pathogenic
1527485	GRCh37/hg19 9p24.3-22.2(chr9:203861-16856907)	Pathogenic
152906	GRCh38/hg38 9p24.3-24.1(chr9:185579-7635806)x1	Pathogenic
152907	GRCh38/hg38 9p24.3-23(chr9:211086-11457340)x1	Pathogenic
152943	GRCh38/hg38 9p24.3-22.3(chr9:322690-16401656)x1	Pathogenic
153821	GRCh38/hg38 9p24.3-24.1(chr9:203861-8172957)x1	Pathogenic

SpliceAI

2131 predictions. Top by Δscore:

Variant	Effect	Δscore
5:69355643:TCTTA:T	donor_loss	1.0000
5:69355644:CTTA:C	donor_loss	1.0000
5:69355645:TTAC:T	donor_loss	1.0000
5:69355646:TA:T	donor_loss	1.0000
5:69355791:CTAC:C	acceptor_gain	1.0000
5:69355889:ACT:A	donor_loss	1.0000
5:69355891:TTA:T	donor_loss	1.0000
5:69355892:TAC:T	donor_loss	1.0000
5:69355893:A:AC	donor_gain	1.0000
5:69355893:AC:A	donor_loss	1.0000
5:69355894:C:CG	donor_gain	1.0000
5:69355894:CT:C	donor_gain	1.0000
5:69355894:CTCT:C	donor_gain	1.0000
5:69355949:TTGCT:T	acceptor_gain	1.0000
5:69355950:TGCT:T	acceptor_gain	1.0000
5:69355952:CT:C	acceptor_gain	1.0000
5:69355954:C:CC	acceptor_gain	1.0000
5:69365751:CAGA:C	acceptor_gain	1.0000
5:69365757:T:TC	acceptor_gain	1.0000
5:69365763:C:CT	acceptor_gain	1.0000
5:69365763:CATT:C	acceptor_gain	1.0000
5:69365764:A:C	acceptor_gain	1.0000
5:69365766:T:C	acceptor_gain	1.0000
5:69365766:T:TC	acceptor_gain	1.0000
5:69366498:CTTA:C	donor_loss	1.0000
5:69366499:TTA:T	donor_loss	1.0000
5:69366500:TA:T	donor_loss	1.0000
5:69366501:A:AG	donor_loss	1.0000
5:69366502:CCT:C	donor_loss	1.0000
5:69369934:G:GG	donor_gain	1.0000

AlphaMissense

1463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:4741028:C:A	K20N	0.997
9:4741028:C:G	K20N	0.997
9:4741048:C:G	G14R	0.997
9:4741048:C:T	G14R	0.997
9:4719284:C:G	A99P	0.996
9:4741030:T:G	K20Q	0.996
9:4741032:C:T	G19D	0.996
9:4713047:A:G	W205R	0.995
9:4713047:A:T	W205R	0.995
9:4718492:C:G	D164H	0.995
9:4718495:C:G	D163H	0.995
9:4719303:A:C	F92L	0.995
9:4719303:A:T	F92L	0.995
9:4719305:A:G	F92L	0.995
9:4740974:G:C	S38R	0.995
9:4740974:G:T	S38R	0.995
9:4740976:T:G	S38R	0.995
9:4741029:T:A	K20M	0.995
9:4741048:C:A	G14W	0.995
9:4718464:A:G	L173P	0.994
9:4719153:G:C	F142L	0.994
9:4719153:G:T	F142L	0.994
9:4719155:A:G	F142L	0.994
9:4719172:C:G	R136P	0.994
9:4719285:C:A	Q98H	0.994
9:4719285:C:G	Q98H	0.994
9:4719301:G:T	P93Q	0.994
9:4722610:G:T	A56D	0.994
9:4740960:C:G	R43P	0.994
9:4741038:C:T	G17D	0.994

dbSNP variants (sampled 300 via entrez): RS1000030922 (9:4740224 A>G), RS1000096916 (9:4734410 G>C), RS1000190477 (9:4741966 G>A,T), RS1000221215 (9:4712205 TAC>T), RS1000223716 (9:4730321 G>C,T), RS1000244429 (9:4741634 C>T), RS1000251398 (9:4738292 A>G), RS1000295363 (9:4714708 A>C,G), RS1000346634 (9:4730895 T>A,C), RS1000388456 (9:4720302 T>A), RS1000421355 (9:4716468 G>A), RS1000554863 (9:4723012 A>C), RS1000630951 (9:4727483 G>C), RS1000710763 (9:4726735 G>T), RS1000814292 (9:4731388 C>A,T)

Disease associations

OMIM: gene MIM:609290 | disease phenotypes: MIM:158170

GenCC curated gene-disease

Mondo (2): chromosome 9p deletion syndrome (MONDO:0008013), primary ovarian failure (MONDO:0005387)

Orphanet (2): Monosomy 9p syndrome (Orphanet:261112), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C538024	Chromosome 9p Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases oxidation, decreases expression, increases expression, affects cotreatment, increases abundance	4
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
bisphenol S	affects cotreatment, decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, increases activity, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
sodium arsenite	increases expression, increases abundance	1
cobaltous chloride	increases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2RC	Abcam HEK293T AK3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

76 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
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
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
NCT04586400	Not specified	RECRUITING	Chromosome 9 P Minus Syndrome
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
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure