ADCK2

Summary

ADCK2 (aarF domain containing kinase 2, HGNC:19039) is a protein-coding gene on chromosome 7q34, encoding Uncharacterized aarF domain-containing protein kinase 2 (Q7Z695). The function of this protein is not yet clear.

Predicted to enable ATP binding activity and protein serine/threonine kinase activity. Involved in regulation of ubiquinone biosynthetic process. Located in mitochondrion.

Source: NCBI Gene 90956 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 129 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_052853

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19039
Approved symbol	ADCK2
Name	aarF domain containing kinase 2
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	MGC20727
Ensembl gene	ENSG00000133597
Ensembl biotype	protein_coding
OMIM	621162
Entrez	90956

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 retained_intron

ENST00000072869, ENST00000473512, ENST00000476491, ENST00000483369, ENST00000498423, ENST00000896692, ENST00000896693, ENST00000896694, ENST00000896695, ENST00000896696, ENST00000896697, ENST00000896698, ENST00000896699, ENST00000926714, ENST00000926715, ENST00000926716, ENST00000926717, ENST00000953389, ENST00000953390

RefSeq mRNA: 1 — MANE Select: NM_052853 NM_052853

CCDS: CCDS5861

Canonical transcript exons

ENST00000072869 — 8 exons

Exon	Start	End
ENSE00000360284	140694663	140695110
ENSE00000727239	140689597	140689725
ENSE00000727245	140690760	140690813
ENSE00001207516	140674611	140674757
ENSE00001267723	140686990	140687241
ENSE00003470100	140681042	140681137
ENSE00003683980	140679155	140679283
ENSE00003847035	140672945	140674263

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 91.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5082 / max 215.6569, expressed in 1794 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81507	13.0718	1794
204792	0.4364	240

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.10	gold quality
cortical plate	UBERON:0005343	90.18	gold quality
amniotic fluid	UBERON:0000173	90.11	gold quality
prefrontal cortex	UBERON:0000451	89.82	gold quality
mucosa of transverse colon	UBERON:0004991	89.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.92	gold quality
spinal cord	UBERON:0002240	88.41	gold quality
skin of leg	UBERON:0001511	88.16	gold quality
endothelial cell	CL:0000115	88.06	gold quality
skin of abdomen	UBERON:0001416	87.96	gold quality
nipple	UBERON:0002030	87.60	gold quality
zone of skin	UBERON:0000014	87.31	gold quality
tendon of biceps brachii	UBERON:0008188	87.00	gold quality
frontal cortex	UBERON:0001870	86.94	gold quality
frontal lobe	UBERON:0016525	86.94	gold quality
neocortex	UBERON:0001950	86.73	gold quality
right frontal lobe	UBERON:0002810	86.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.60	gold quality
penis	UBERON:0000989	86.50	gold quality
lower esophagus mucosa	UBERON:0035834	86.45	gold quality
cingulate cortex	UBERON:0003027	86.17	gold quality
type B pancreatic cell	CL:0000169	86.16	gold quality
anterior cingulate cortex	UBERON:0009835	86.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.13	gold quality
hypothalamus	UBERON:0001898	86.11	gold quality
tongue squamous epithelium	UBERON:0006919	86.04	gold quality
epithelium of esophagus	UBERON:0001976	86.03	gold quality
inferior vagus X ganglion	UBERON:0005363	85.94	gold quality
mammalian vulva	UBERON:0000997	85.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	137.78
E-ANND-3	no	2.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting ADCK2, 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-3692-3P	99.98	70.27	2139
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-4433B-5P	95.91	66.56	727

Literature-anchored findings (GeneRIF, showing 1)

• ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin (PMID:25967120)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adck2	ENSDARG00000073923
mus_musculus	Adck2	ENSMUSG00000046947
rattus_norvegicus	Ndufb2	ENSRNOG00000010005
caenorhabditis_elegans		WBGENE00021315

Paralogs (4): ADCK1 (ENSG00000063761), COQ8B (ENSG00000123815), COQ8A (ENSG00000163050), ADCK5 (ENSG00000173137)

Protein

Protein identifiers

Uncharacterized aarF domain-containing protein kinase 2 — Q7Z695 (reviewed: Q7Z695)

All UniProt accessions (5): A4D1T6, C9JE15, Q7Z695, H7C4I2, H7C5M5

UniProt curated annotations — full annotation on UniProt →

Function. The function of this protein is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr). Involved in the mitochondrial import of CoQ precursors, plays a role in muscle mitochondrial function and fatty acid beta-oxidation.

Subcellular location. Mitochondrion. Membrane.

Similarity. Belongs to the protein kinase superfamily. ADCK protein kinase family.

RefSeq proteins (1): NP_443085* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004147	ABC1_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR044095	ADCK2_dom	Domain
IPR052402	ADCK_kinase	Family

Pfam: PF03109

UniProt features (13 total): sequence variant 7, binding site 2, chain 1, transmembrane region 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z695-F1	72.45	0.49

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): 445 (proton acceptor)

Ligand- & substrate-binding residues (2): 206–214; 311

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, FISCHER_G1_S_CELL_CYCLE, GOBP_KETONE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_REGULATION_OF_KETONE_METABOLIC_PROCESS, GOBP_KETONE_BIOSYNTHETIC_PROCESS, MODULE_207, GOBP_QUINONE_METABOLIC_PROCESS, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C

GO Biological Process (2): regulation of ubiquinone biosynthetic process (GO:0010795), protein phosphorylation (GO:0006468)

GO Molecular Function (7): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ubiquinone biosynthetic process	1
regulation of ketone biosynthetic process	1
phosphorylation	1
protein modification process	1
protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADCK2	COQ8A	Q8NI60	729
ADCK2	COQ8B	Q96D53	714
ADCK2	COQ3	Q9NZJ6	638
ADCK2	COQ4	Q9Y3A0	615
ADCK2	COQ5	Q5HYK3	593
ADCK2	COQ9	O75208	535
ADCK2	ADCK1	Q86TW2	530
ADCK2	ADCK5	Q3MIX3	523
ADCK2	COQ7	Q99807	509
ADCK2	COQ2	Q96H96	506
ADCK2	PDSS1	Q5T2R2	487
ADCK2	COQ6	Q9Y2Z9	478
ADCK2	PDSS2	Q86YH6	450
ADCK2	COQ10A	Q96MF6	448
ADCK2	COQ10B	Q9H8M1	428

IntAct

46 interactions, top by confidence:

A	B	Type	Score
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
LRRC8B	SLC25A17	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
TMCO3	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC4A8	ABCC4	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
NMUR2	TMEM63A	psi-mi:“MI:0914”(association)	0.350
ADCK2	SLC25A5	psi-mi:“MI:0914”(association)	0.350
ADCK2	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
ADCK2	ILVBL	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
IL17RC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350
KCNMB3	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PTCHD3	ABCD4	psi-mi:“MI:0914”(association)	0.350
CD3D	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): ADCK2 (Affinity Capture-MS), PDK2 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), GPI (Affinity Capture-MS), PMPCB (Affinity Capture-MS), NRD1 (Affinity Capture-MS), CLPB (Affinity Capture-MS), MRPL22 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS)

ESM2 similar proteins: A4II32, A7MCT6, D3ZRW8, G5E872, O35465, O54783, O55229, P50747, P61797, Q14164, Q14318, Q14CH1, Q1JP61, Q3B7U9, Q496Y0, Q497B8, Q52WX2, Q5I0I5, Q7TQC5, Q7YRZ1, Q7YRZ2, Q7Z2E3, Q7Z695, Q80WC9, Q8BNV1, Q8BYN3, Q8CGA0, Q8HXH0, Q8IYL2, Q8IZ69, Q8K4H4, Q8N371, Q8NF37, Q8NI29, Q8QZX0, Q920N2, Q96EN8, Q9BGQ0, Q9CXT6, Q9D2Q2

Diamond homologs: Q02981, Q43924, Q55G83, Q6NSR3, Q7Z695, Q9P7M0, A0A172M468, A0A179HKZ8, A0KEF8, A0L1M6, A1RP80, A1SAK0, A1TTA2, A1U669, A1V750, A1W4D7, A2S8L4, A3D9F4, A3MNU1, A3N5V1, A3NRJ7, A3QIE3, A4STK9, A4XPM5, A4Y2Q3, A5F4G3, A5WA47, A6VDI8, A6WIE7, A7MQL5, A7MTX4, A8H968, A9BP42, A9KYL6, B0KM38, B1J2S6, B1KR05, B1XWR5, B3PH50, B5FF80

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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
Transport of small molecules	8	5.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	96
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1807754	GRCh37/hg19 7q32.3-36.1(chr7:131779213-149042734)x1	Pathogenic
2425073	NC_000007.13:g.(?138391369)(141759786_?)del	Pathogenic
3391898	GRCh37/hg19 7q33-36.1(chr7:136304444-148292957)x1	Pathogenic
617479	Single allele	Likely pathogenic

SpliceAI

1280 predictions. Top by Δscore:

Variant	Effect	Δscore
7:140674606:GACA:G	acceptor_loss	1.0000
7:140674608:CA:C	acceptor_loss	1.0000
7:140674610:GGT:G	acceptor_gain	1.0000
7:140674754:ACAG:A	donor_gain	1.0000
7:140674755:CAG:C	donor_gain	1.0000
7:140674756:AGG:A	donor_loss	1.0000
7:140674758:G:GG	donor_gain	1.0000
7:140674758:GTGA:G	donor_loss	1.0000
7:140679152:TA:T	acceptor_loss	1.0000
7:140679153:A:AG	acceptor_gain	1.0000
7:140679153:AGATT:A	acceptor_gain	1.0000
7:140679154:G:GA	acceptor_gain	1.0000
7:140679154:G:GC	acceptor_loss	1.0000
7:140679154:GATT:G	acceptor_gain	1.0000
7:140679154:GATTG:G	acceptor_gain	1.0000
7:140679260:G:GT	donor_gain	1.0000
7:140679270:TGGAA:T	donor_gain	1.0000
7:140679271:GGAAA:G	donor_gain	1.0000
7:140679281:G:GT	donor_gain	1.0000
7:140679281:GAA:G	donor_gain	1.0000
7:140679284:G:GG	donor_gain	1.0000
7:140681037:T:TA	acceptor_gain	1.0000
7:140687202:G:GT	donor_gain	1.0000
7:140687239:CAGG:C	donor_loss	1.0000
7:140687240:AG:A	donor_loss	1.0000
7:140687241:GGTGA:G	donor_loss	1.0000
7:140687242:G:A	donor_loss	1.0000
7:140687243:T:G	donor_loss	1.0000
7:140689593:CCAG:C	acceptor_loss	1.0000
7:140689595:A:AG	acceptor_gain	1.0000

AlphaMissense

4022 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:140674262:A:T	K311I	0.999
7:140674263:A:C	K311N	0.999
7:140674263:A:T	K311N	0.999
7:140687009:T:A	V442D	0.999
7:140687162:A:T	D493V	0.999
7:140673771:A:C	K147N	0.998
7:140673771:A:T	K147N	0.998
7:140673781:T:A	W151R	0.998
7:140673781:T:C	W151R	0.998
7:140674261:A:C	K311Q	0.998
7:140674261:A:G	K311E	0.998
7:140674734:T:C	F353L	0.998
7:140674736:T:A	F353L	0.998
7:140674736:T:G	F353L	0.998
7:140679227:T:C	F385L	0.998
7:140679229:C:A	F385L	0.998
7:140679229:C:G	F385L	0.998
7:140687018:A:T	D445V	0.998
7:140673776:G:A	G149D	0.997
7:140673783:G:C	W151C	0.997
7:140673783:G:T	W151C	0.997
7:140679173:G:C	A367P	0.997
7:140679203:T:C	F377L	0.997
7:140679205:C:A	F377L	0.997
7:140679205:C:G	F377L	0.997
7:140687042:T:A	V453D	0.997
7:140687162:A:C	D493A	0.997
7:140673769:A:G	K147E	0.996
7:140673780:G:C	Q150H	0.996
7:140673780:G:T	Q150H	0.996

dbSNP variants (sampled 300 via entrez): RS1000308372 (7:140684226 G>C), RS1000345757 (7:140690438 A>C,G), RS1000388316 (7:140674494 T>A), RS1000420817 (7:140690883 G>A), RS1000724997 (7:140676352 A>G), RS1000947785 (7:140678908 A>AG), RS1001021343 (7:140678719 T>C), RS1001181598 (7:140675041 G>A,C), RS1001264893 (7:140672691 C>T), RS1001696834 (7:140691620 G>A,C), RS1001739570 (7:140681652 C>T), RS1001771669 (7:140684554 C>CGGATAGG), RS1001858858 (7:140672097 G>A), RS1001876536 (7:140691314 C>G,T), RS1002098091 (7:140684291 C>T)

Disease associations

OMIM: gene MIM:621162 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): RASopathy (MONDO:0021060)

Orphanet (1): RASopathy (Orphanet:536391)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — ABC1-A subfamily

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	8
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	2
Smoke	decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects 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
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cisplatin	affects expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Silicon Dioxide	decreases expression	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1J2	Abcam HeLa ADCK2 KO	Cancer cell line	Female
CVCL_SB58	HAP1 ADCK2 (-) 1	Cancer cell line	Male
CVCL_SB59	HAP1 ADCK2 (-) 2	Cancer cell line	Male
CVCL_SB60	HAP1 ADCK2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06489067	Not specified	RECRUITING	Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)
NCT06776380	Not specified	RECRUITING	Pubertal Development in Patients with RASopathies
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07344480	Not specified	RECRUITING	Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)
NCT07464821	Not specified	RECRUITING	National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype