ATP23

Summary

ATP23 (ATP23 metallopeptidase and ATP synthase assembly factor homolog, HGNC:29452) is a protein-coding gene on chromosome 12q14.1, encoding Mitochondrial inner membrane protease ATP23 homolog (Q9Y6H3). It is a selective cancer dependency (DepMap: 18.9% of cell lines).

The protein encoded by this gene is amplified in glioblastomas and interacts with the DNA binding subunit of DNA-dependent protein kinase. This kinase is involved in double-strand break repair (DSB), and higher expression of the encoded protein increases the efficiency of DSB. In addition, comparison to orthologous proteins strongly suggests that this protein is a metalloprotease important in the biosynthesis of mitochondrial ATPase. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 91419 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 13 total
• Cancer dependency (DepMap): dependent in 18.9% of screened cell lines
• MANE Select transcript: NM_033276

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29452
Approved symbol	ATP23
Name	ATP23 metallopeptidase and ATP synthase assembly factor homolog
Location	12q14.1
Locus type	gene with protein product
Status	Approved
Aliases	KUB3
Ensembl gene	ENSG00000166896
Ensembl biotype	protein_coding
OMIM	619760
Entrez	91419

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000300145, ENST00000546709, ENST00000549257, ENST00000551997, ENST00000647763, ENST00000874176, ENST00000926335, ENST00000926336

RefSeq mRNA: 4 — MANE Select: NM_033276 NM_001320408, NM_001320409, NM_001320410, NM_033276

CCDS: CCDS41802

Canonical transcript exons

ENST00000300145 — 6 exons

Exon	Start	End
ENSE00001107586	57941567	57941888
ENSE00001107587	57956687	57959148
ENSE00002455772	57945628	57945673
ENSE00003491231	57946995	57947076
ENSE00003564497	57951758	57951895
ENSE00003573232	57953606	57953689

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 92.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3562 / max 153.3982, expressed in 1706 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126339	4.4594	1539
126341	1.4861	748
126342	1.2788	681
126340	0.1318	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	92.65	gold quality
left testis	UBERON:0004533	92.62	gold quality
testis	UBERON:0000473	91.71	gold quality
mucosa of transverse colon	UBERON:0004991	88.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.18	gold quality
gastrocnemius	UBERON:0001388	86.64	gold quality
muscle of leg	UBERON:0001383	86.50	gold quality
skeletal muscle tissue	UBERON:0001134	85.96	gold quality
bone marrow	UBERON:0002371	84.43	gold quality
granulocyte	CL:0000094	83.76	gold quality
transverse colon	UBERON:0001157	83.34	gold quality
leukocyte	CL:0000738	82.86	gold quality
monocyte	CL:0000576	82.84	gold quality
muscle tissue	UBERON:0002385	82.84	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.45	gold quality
bone marrow cell	CL:0002092	82.31	gold quality
rectum	UBERON:0001052	81.31	gold quality
colon	UBERON:0001155	81.23	gold quality
adipose tissue	UBERON:0001013	81.12	gold quality
stromal cell of endometrium	CL:0002255	80.85	gold quality
lower esophagus mucosa	UBERON:0035834	80.65	gold quality
cerebellar cortex	UBERON:0002129	80.54	gold quality
cerebellum	UBERON:0002037	80.51	gold quality
cerebellar hemisphere	UBERON:0002245	80.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.82	gold quality
intestine	UBERON:0000160	79.77	gold quality
body of pancreas	UBERON:0001150	79.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.53
E-MTAB-7381	no	261.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting ATP23, 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-4776-3P	100.00	68.73	1340
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-135A-2-3P	98.40	66.74	442
HSA-MIR-135B-3P	98.40	67.35	426
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• The data provide the first evidence for a link between the level of KUB3 amplification and expression in glioma and DSB repair efficiency. (PMID:23670597)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp23	ENSDARG00000063686
mus_musculus	Atp23	ENSMUSG00000025436
rattus_norvegicus	Atp23	ENSRNOG00000045629
drosophila_melanogaster	CG5131	FBGN0032644

Protein

Protein identifiers

Mitochondrial inner membrane protease ATP23 homolog — Q9Y6H3 (reviewed: Q9Y6H3)

Alternative names: Ku70-binding protein 3, XRCC6-binding protein 1

All UniProt accessions (2): Q9Y6H3, H0YIJ9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with XRCC6.

Similarity. Belongs to the peptidase M76 family.

RefSeq proteins (4): NP_001307337, NP_001307338, NP_001307339, NP_150592* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019165	Peptidase_M76_ATP23	Family

Pfam: PF09768

UniProt features (5 total): binding site 2, chain 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6H3-F1	81.25	0.67

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): 126

Ligand- & substrate-binding residues (2): 125; 129

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, KAUFFMANN_DNA_REPAIR_GENES, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_PROTEIN_MATURATION, MODULE_205, GOBP_DNA_DAMAGE_RESPONSE, FISCHER_DREAM_TARGETS, CUI_TCF21_TARGETS_2_UP, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOCC_DNA_REPAIR_COMPLEX, GOBP_PROTEOLYSIS, GOBP_DNA_METABOLIC_PROCESS, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY

GO Biological Process (4): double-strand break repair via nonhomologous end joining (GO:0006303), mitochondrial proton-transporting ATP synthase complex assembly (GO:0033615), mitochondrial protein processing (GO:0034982), proteolysis (GO:0006508)

GO Molecular Function (7): metalloendopeptidase activity (GO:0004222), DNA-dependent protein kinase activity (GO:0004677), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (5): mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), DNA-dependent protein kinase-DNA ligase 4 complex (GO:0005958), cell junction (GO:0030054)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
cytoplasm	2
cellular anatomical structure	2
double-strand break repair	1
mitochondrial respiratory chain complex assembly	1
proton-transporting ATP synthase complex assembly	1
protein processing	1
protein metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
protein serine/threonine kinase activity	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
nonhomologous end joining complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP23	CHCHD4	Q8N4Q1	871
ATP23	PHB1	P35232	675
ATP23	TIMM10	P62072	666
ATP23	TIMM9	Q9Y5J7	656
ATP23	GFER	P55789	647
ATP23	OXA1L	Q15070	625
ATP23	ATPAF1	Q5TC12	615
ATP23	OMA1	Q96E52	608
ATP23	ATPAF2	Q8N5M1	607
ATP23	TRIAP1	O43715	605
ATP23	CIAPIN1	Q6FI81	603
ATP23	COX17	Q14061	583
ATP23	MT-ATP6	P00846	578
ATP23	C22orf39	Q6P5X5	570
ATP23	XPNPEP3	Q9NQH7	543

IntAct

123 interactions, top by confidence:

A	B	Type	Score
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
NUP35	KCTD9	psi-mi:“MI:0914”(association)	0.870
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
DUSP21	ATP23	psi-mi:“MI:0915”(physical association)	0.560
BAG4	ATP23	psi-mi:“MI:0915”(physical association)	0.560
ABI2	ATP23	psi-mi:“MI:0915”(physical association)	0.560
FRS3	ATP23	psi-mi:“MI:0915”(physical association)	0.560
ATG5	ATP23	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	ATP23	psi-mi:“MI:0915”(physical association)	0.560
KLC3	ATP23	psi-mi:“MI:0915”(physical association)	0.560
HR	ATP23	psi-mi:“MI:0915”(physical association)	0.560
PLSCR4	ATP23	psi-mi:“MI:0915”(physical association)	0.560
	ATP23	psi-mi:“MI:0915”(physical association)	0.560
GLYCTK	ATP23	psi-mi:“MI:0915”(physical association)	0.560
ZIC1	ATP23	psi-mi:“MI:0915”(physical association)	0.560
PPP1R16A	ATP23	psi-mi:“MI:0915”(physical association)	0.560
EXOC8	ATP23	psi-mi:“MI:0915”(physical association)	0.560
STK16	ATP23	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T	ATP23	psi-mi:“MI:0915”(physical association)	0.560
AIRIM	ATP23	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	ATP23	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	ATP23	psi-mi:“MI:0915”(physical association)	0.560
FOXI1	ATP23	psi-mi:“MI:0915”(physical association)	0.560
ACTN3	ATP23	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	ATP23	psi-mi:“MI:0915”(physical association)	0.560
GUCD1	ATP23	psi-mi:“MI:0915”(physical association)	0.560
CCDC120	ATP23	psi-mi:“MI:0915”(physical association)	0.560
CTNNA3	ATP23	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (73): XRCC6BP1 (Two-hybrid), XRCC6BP1 (Two-hybrid), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS), XRCC6BP1 (Affinity Capture-MS)

ESM2 similar proteins: A4IGF3, A7E2Z9, F4HXW9, O18756, O35099, O43556, O43909, O70258, O94923, O95299, P0CB89, P0CQ26, P0CQ27, P97259, Q08834, Q09328, Q0MQB6, Q0MQB7, Q29AK2, Q29S03, Q4R5B1, Q5BKJ4, Q5HYA8, Q5NDE5, Q5RAP2, Q5ZJT0, Q69ZX6, Q6IQC7, Q6YAT4, Q7T0P7, Q8BR76, Q8C1F4, Q8IYB8, Q8K1B9, Q8N6G5, Q8R4G6, Q8R4K8, Q8VXZ5, Q8W486, Q99683

Diamond homologs: A1CSI6, A1DG72, A2QKG2, A3LYB6, A4IGF3, A4RF31, A5DB08, A5DYI1, A6RCS8, A6SSS5, A6ZS94, A7ETJ6, A7TQM0, A8QA10, C8ZFP7, P0CQ26, P0CQ27, P53722, Q0U6H9, Q1E910, Q1MTR0, Q2H8S7, Q2TZA3, Q4P5B3, Q4X261, Q55CA5, Q59Z51, Q5B0W4, Q5BKJ4, Q6BK77, Q6C253, Q6CTY3, Q6FIY7, Q75EL5, Q7RYM1, Q7T0P7, Q9CWQ3, Q9SRP6, Q9Y6H3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

966 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57941851:G:GT	donor_gain	1.0000
12:57941884:GACAA:G	donor_gain	1.0000
12:57941889:G:GG	donor_gain	1.0000
12:57946993:A:AG	acceptor_gain	1.0000
12:57946994:G:GA	acceptor_gain	1.0000
12:57951757:GAT:G	acceptor_gain	1.0000
12:57951757:GATA:G	acceptor_gain	1.0000
12:57956685:A:AG	acceptor_gain	1.0000
12:57956686:G:GG	acceptor_gain	1.0000
12:57956686:GACTT:G	acceptor_gain	1.0000
12:57941906:G:GT	donor_gain	0.9900
12:57941909:G:GT	donor_gain	0.9900
12:57941914:G:GA	donor_gain	0.9900
12:57941928:GGTC:G	donor_gain	0.9900
12:57941950:G:GT	donor_gain	0.9900
12:57946994:GTGCT:G	acceptor_gain	0.9900
12:57951753:CCTA:C	acceptor_loss	0.9900
12:57951755:TA:T	acceptor_loss	0.9900
12:57951756:A:AG	acceptor_gain	0.9900
12:57951757:G:GG	acceptor_gain	0.9900
12:57951757:G:T	acceptor_loss	0.9900
12:57951892:AGAGG:A	donor_loss	0.9900
12:57951893:GAG:G	donor_gain	0.9900
12:57951894:AGGT:A	donor_loss	0.9900
12:57951896:G:GA	donor_loss	0.9900
12:57951896:G:GG	donor_gain	0.9900
12:57951897:T:G	donor_loss	0.9900
12:57956681:TTTTA:T	acceptor_loss	0.9900
12:57956682:TTTA:T	acceptor_loss	0.9900
12:57956684:TAGA:T	acceptor_loss	0.9900

AlphaMissense

1642 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57951822:T:C	L127P	0.996
12:57947056:T:C	F99L	0.992
12:57947058:T:A	F99L	0.992
12:57947058:T:G	F99L	0.992
12:57953624:A:C	S158R	0.992
12:57953626:T:A	S158R	0.992
12:57953626:T:G	S158R	0.992
12:57951810:T:A	V123D	0.991
12:57953607:T:A	V152D	0.991
12:57956763:T:A	V205D	0.991
12:57951827:C:G	H129D	0.990
12:57956784:G:A	C212Y	0.990
12:57956785:T:G	C212W	0.990
12:57951767:T:A	C109S	0.989
12:57951768:G:C	C109S	0.989
12:57951846:G:C	R135P	0.989
12:57953633:T:A	C161S	0.989
12:57953634:G:C	C161S	0.989
12:57951833:T:C	F131L	0.987
12:57951835:T:A	F131L	0.987
12:57951835:T:G	F131L	0.987
12:57951837:A:C	D132A	0.987
12:57951837:A:T	D132V	0.987
12:57953612:G:C	A154P	0.987
12:57953615:G:C	A155P	0.987
12:57953622:T:C	L157P	0.987
12:57956706:C:A	A186D	0.987
12:57951830:G:C	A130P	0.986
12:57951836:G:C	D132H	0.986
12:57956705:G:C	A186P	0.986

dbSNP variants (sampled 300 via entrez): RS1000233457 (12:57941958 T>C), RS1000240419 (12:57956051 G>A), RS1000460596 (12:57957262 T>G), RS1000500735 (12:57941571 C>A,T), RS1000748061 (12:57956849 A>G), RS1000845222 (12:57951208 C>T), RS1000979197 (12:57943376 T>C), RS1001075749 (12:57944472 T>C), RS1001181347 (12:57958453 C>G), RS1001328945 (12:57955130 C>A,T), RS1001607456 (12:57941276 C>G), RS1001833120 (12:57958488 C>A), RS1001849256 (12:57947658 C>G,T), RS1001947614 (12:57958668 C>T), RS1001974132 (12:57942532 T>C)

Disease associations

OMIM: gene MIM:619760 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004748_24	Lung cancer	3.000000e-07
GCST009144_6	Disease progression in age-related macular degeneration (adjusted for baseline)	4.000000e-06
GCST010988_496	Adult body size	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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, affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression	3
methylmercuric chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
bromoacetate	decreases expression	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
riccardin D	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	increases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Methotrexate	increases expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases 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_D8ZQ	Ubigene HEK293 ATP23 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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