ATPSCKMT

Summary

ATPSCKMT (ATP synthase c subunit lysine N-methyltransferase, HGNC:27029) is a protein-coding gene on chromosome 5p15.2, encoding ATP synthase subunit C lysine N-methyltransferase (Q6P4H8). Mitochondrial protein-lysine N-methyltransferase that trimethylates ATP synthase subunit C, ATP5MC1 and ATP5MC2.

Enables protein-lysine N-methyltransferase activity. Involved in several processes, including peptidyl-lysine trimethylation; positive regulation of proton-transporting ATP synthase activity, rotational mechanism; and positive regulation of sensory perception of pain. Located in mitochondrial crista.

Source: NCBI Gene 134145 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_199133

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27029
Approved symbol	ATPSCKMT
Name	ATP synthase c subunit lysine N-methyltransferase
Location	5p15.2
Locus type	gene with protein product
Status	Approved
Aliases	JS-2
Ensembl gene	ENSG00000150756
Ensembl biotype	protein_coding
OMIM	618568
Entrez	134145

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000280330, ENST00000504390, ENST00000506108, ENST00000508553, ENST00000510047, ENST00000510052, ENST00000511437, ENST00000932928

RefSeq mRNA: 3 — MANE Select: NM_199133 NM_001258388, NM_001258389, NM_199133

CCDS: CCDS43301, CCDS58942

Canonical transcript exons

ENST00000511437 — 5 exons

Exon	Start	End
ENSE00002083313	10225507	10227647
ENSE00003512247	10249858	10249888
ENSE00003523778	10236478	10236615
ENSE00003661639	10239067	10239356
ENSE00003662389	10235211	10235261

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 88.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5720 / max 186.5970, expressed in 1658 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60881	6.5720	1658

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	88.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.42	gold quality
islet of Langerhans	UBERON:0000006	86.68	gold quality
adrenal tissue	UBERON:0018303	86.61	gold quality
stromal cell of endometrium	CL:0002255	85.57	gold quality
epithelial cell of pancreas	CL:0000083	84.70	silver quality
rectum	UBERON:0001052	84.34	gold quality
monocyte	CL:0000576	84.28	gold quality
hypothalamus	UBERON:0001898	84.08	gold quality
leukocyte	CL:0000738	83.83	gold quality
right adrenal gland	UBERON:0001233	83.61	gold quality
right adrenal gland cortex	UBERON:0035827	83.16	gold quality
medial globus pallidus	UBERON:0002477	82.95	gold quality
left adrenal gland	UBERON:0001234	82.92	gold quality
smooth muscle tissue	UBERON:0001135	82.89	gold quality
gall bladder	UBERON:0002110	82.57	gold quality
substantia nigra	UBERON:0002038	82.55	gold quality
adrenal gland	UBERON:0002369	82.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.18	gold quality
left adrenal gland cortex	UBERON:0035825	82.11	gold quality
corpus callosum	UBERON:0002336	82.01	gold quality
parotid gland	UBERON:0001831	81.79	silver quality
pituitary gland	UBERON:0000007	81.62	gold quality
middle temporal gyrus	UBERON:0002771	81.48	gold quality
adrenal cortex	UBERON:0001235	81.47	gold quality
endothelial cell	CL:0000115	81.46	silver quality
midbrain	UBERON:0001891	81.33	gold quality
adenohypophysis	UBERON:0002196	81.29	gold quality
spinal cord	UBERON:0002240	81.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting ATPSCKMT, 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-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6758-3P	99.57	67.55	1078

Literature-anchored findings (GeneRIF, showing 4)

• Genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer. (PMID:21802380)
• we uncover a role for methyltransferase activity of FAM173B in the neurobiology of pain. These results also highlight FAM173B methyltransferase activity as a potential therapeutic target to treat debilitating chronic pain conditions (PMID:29444090)
• It has been identified FAM173B as the long-sought KMT responsible for methylation of ATP synthase c-subunit (ATPSc), a key protein in cellular ATP production, and have demonstrated functional significance of ATPSc methylation. (PMID:30530489)
• Expression of mitochondrial TSPO and FAM173B is associated with inflammation and symptoms in patients with painful knee osteoarthritis. (PMID:33067627)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atpsckmt	ENSDARG00000033451
mus_musculus	Atpsckmt	ENSMUSG00000039065
rattus_norvegicus	Atpsckmt	ENSRNOG00000022347
drosophila_melanogaster	CG3337	FBGN0038871
caenorhabditis_elegans		WBGENE00012658

Paralogs (1): ANTKMT (ENSG00000103254)

Protein

Protein identifiers

ATP synthase subunit C lysine N-methyltransferase — Q6P4H8 (reviewed: Q6P4H8)

Alternative names: Protein N-lysine methyltransferase FAM173B

All UniProt accessions (4): Q6P4H8, D6RBE3, D6RIE0, J3KN90

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial protein-lysine N-methyltransferase that trimethylates ATP synthase subunit C, ATP5MC1 and ATP5MC2. Trimethylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration. Promotes chronic pain. Involved in persistent inflammatory and neuropathic pain: methyltransferase activity in the mitochondria of sensory neurons promotes chronic pain via a pathway that depends on the production of reactive oxygen species (ROS) and on the engagement of spinal cord microglia.

Subcellular location. Mitochondrion membrane.

Tissue specificity. Ubiquitously expressed.

Domain organisation. Contains an atypical, non-cleavable mitochondrial targeting sequence responsible for its localization to mitochondria.

Similarity. Belongs to the ANT/ATPSC lysine N-methyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P4H8-1	1	yes
Q6P4H8-2	2

RefSeq proteins (3): NP_001245317, NP_001245318, NP_954584* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026170	FAM173A/B	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[protein] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:54192)

UniProt features (11 total): sequence variant 4, mutagenesis site 2, chain 1, transmembrane region 1, region of interest 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P4H8-F1	82.18	0.63

Functional residue map

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

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
117	abolished protein-lysine n-methyltransferase activity.
94	abolished protein-lysine n-methyltransferase activity and ability to promote chronic pain.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT

GO Biological Process (6): peptidyl-lysine methylation (GO:0018022), peptidyl-lysine trimethylation (GO:0018023), positive regulation of sensory perception of pain (GO:1904058), positive regulation of proton-transporting ATP synthase activity, rotational mechanism (GO:1905273), regulation of mitochondrial ATP synthesis coupled proton transport (GO:1905706), methylation (GO:0032259)

GO Molecular Function (7): protein-lysine N-methyltransferase activity (GO:0016279), protein binding (GO:0005515), methyltransferase activity (GO:0008168), N-methyltransferase activity (GO:0008170), protein methyltransferase activity (GO:0008276), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial crista (GO:0030061), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
methyltransferase activity	3
cellular anatomical structure	2
protein methylation	1
peptidyl-lysine modification	1
peptidyl-lysine methylation	1
sensory perception of pain	1
positive regulation of nervous system process	1
regulation of sensory perception of pain	1
proton-transporting ATP synthase activity, rotational mechanism	1
positive regulation of ligase activity	1
positive regulation of cation channel activity	1
proton motive force-driven mitochondrial ATP synthesis	1
regulation of ATP biosynthetic process	1
metabolic process	1
protein methyltransferase activity	1
lysine N-methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity, acting on a protein	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial inner membrane	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATPSCKMT	CMBL	Q96DG6	883
ATPSCKMT	CCT5	P48643	674
ATPSCKMT	EEF1AKMT1	Q8WVE0	525
ATPSCKMT	METTL18	O95568	503
ATPSCKMT	METTL22	Q9BUU2	495
ATPSCKMT	EEF1AKMT2	Q5JPI9	489
ATPSCKMT	VCPKMT	Q9H867	489
ATPSCKMT	METTL21A	Q8WXB1	487
ATPSCKMT	TULP4	Q9NRJ4	468
ATPSCKMT	IGDCC4	Q8TDY8	458
ATPSCKMT	METTL13	Q8N6R0	452
ATPSCKMT	EEF2KMT	Q96G04	452
ATPSCKMT	METTL23	Q86XA0	434
ATPSCKMT	EPRS1	P07814	373
ATPSCKMT	ECH1	Q13011	368

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MEOX2	ATPSCKMT	psi-mi:“MI:0915”(physical association)	0.560
ATPSCKMT	POTEI	psi-mi:“MI:0914”(association)	0.350
ATPSCKMT	POTEF	psi-mi:“MI:0914”(association)	0.350
ATPSCKMT	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): FAM173B (Affinity Capture-RNA), FAM173B (Two-hybrid), FAM173B (Affinity Capture-RNA), SUFU (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), S100A3 (Affinity Capture-MS), POTEI (Affinity Capture-MS), PCK1 (Affinity Capture-MS), POTEF (Affinity Capture-MS), FAM173B (Affinity Capture-RNA)

ESM2 similar proteins: A0JN95, A6NJ78, D3ZLY0, G1SPE9, O14717, O22268, O55055, O95453, O95671, P27465, P28492, P37287, P69341, Q05B63, Q08J23, Q0V8R7, Q0VGM9, Q10D00, Q1HFZ0, Q4G073, Q571F8, Q5I0K3, Q5R5T5, Q5R962, Q5R9W8, Q5RC51, Q5RJZ1, Q64323, Q6GR37, Q6H1L8, Q6NYU2, Q6P4H8, Q6YJI5, Q7TNK6, Q7YS61, Q7Z4G4, Q811P6, Q8JZM0, Q8N0X4, Q8R2Y8

Diamond homologs: D3ZLY0, Q501J2, Q5I047, Q6P4H8, Q9BQD7, Q9D1Z3, Q9XX11, A0Q1R2, A1KS36, A5D3Y3, A5I638, A7FXL3, A7GHH4, B1ILM1, B1KZN5, B1XU70, B8F6T6, C1FVT8, C5BEW8, F0NBH8, P44643, P45558, P60091, Q489G6, Q4QNK7, Q5FAH7, Q6MAY1, Q81ZZ9, Q9JW08

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

805 predictions. Top by Δscore:

Variant	Effect	Δscore
5:10239065:A:AC	donor_gain	1.0000
5:10239066:C:CC	donor_gain	1.0000
5:10239066:CAATG:C	donor_gain	1.0000
5:10227645:CAT:C	acceptor_gain	0.9900
5:10227647:TC:T	acceptor_loss	0.9900
5:10227648:C:CC	acceptor_gain	0.9900
5:10227648:CTGTG:C	acceptor_loss	0.9900
5:10227649:T:A	acceptor_loss	0.9900
5:10236616:C:A	acceptor_loss	0.9900
5:10236617:T:A	acceptor_loss	0.9900
5:10239066:CA:C	donor_gain	0.9900
5:10239354:TAC:T	acceptor_gain	0.9900
5:10239356:CCTAG:C	acceptor_loss	0.9900
5:10239357:CTAG:C	acceptor_loss	0.9900
5:10239362:T:TC	acceptor_gain	0.9900
5:10236474:ATAC:A	donor_loss	0.9800
5:10236475:TACCT:T	donor_loss	0.9800
5:10239060:AAC:A	donor_loss	0.9800
5:10239061:ACT:A	donor_loss	0.9800
5:10239062:CTCA:C	donor_loss	0.9800
5:10239064:CACAA:C	donor_loss	0.9800
5:10239065:A:AT	donor_loss	0.9800
5:10239066:C:T	donor_loss	0.9800
5:10239084:T:TT	donor_loss	0.9800
5:10239352:TATAC:T	acceptor_gain	0.9800
5:10239357:C:CC	acceptor_gain	0.9800
5:10227644:GCAT:G	acceptor_gain	0.9700
5:10227645:CATC:C	acceptor_gain	0.9700
5:10236472:ACAT:A	donor_loss	0.9700
5:10236810:AGTTT:A	donor_gain	0.9700

AlphaMissense

1500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:10235226:G:C	F160L	0.995
5:10235226:G:T	F160L	0.995
5:10235228:A:G	F160L	0.995
5:10227579:G:C	F188L	0.994
5:10227579:G:T	F188L	0.994
5:10227581:A:G	F188L	0.994
5:10239082:A:C	S97R	0.993
5:10239082:A:T	S97R	0.993
5:10239084:T:G	S97R	0.993
5:10236499:A:C	F141L	0.992
5:10236499:A:T	F141L	0.992
5:10236501:A:G	F141L	0.992
5:10239163:A:C	F70L	0.992
5:10239163:A:T	F70L	0.992
5:10239165:A:G	F70L	0.992
5:10239071:C:G	R101P	0.991
5:10239074:C:A	G100V	0.991
5:10236500:A:G	F141S	0.987
5:10236561:A:G	W121R	0.987
5:10236561:A:T	W121R	0.987
5:10239074:C:T	G100E	0.987
5:10236545:G:A	S126F	0.986
5:10227595:A:T	V183D	0.985
5:10236565:G:C	N119K	0.985
5:10236565:G:T	N119K	0.985
5:10236614:A:T	V103D	0.985
5:10235236:A:T	V157D	0.984
5:10236572:T:A	E117V	0.984
5:10236578:C:T	G115D	0.983
5:10239093:C:G	D94H	0.982

dbSNP variants (sampled 300 via entrez): RS1000129122 (5:10233019 T>A,C), RS1000230294 (5:10246359 G>A,C), RS1000344457 (5:10243110 G>A), RS1000430343 (5:10248141 T>C), RS1000734443 (5:10231950 C>A,T), RS1000882877 (5:10226068 A>C,G), RS1001082619 (5:10228776 C>T), RS1001091862 (5:10234919 AACTACATT>A), RS1001304682 (5:10232519 T>C), RS1001438547 (5:10229087 T>C), RS1001463745 (5:10226846 G>A), RS1001715542 (5:10247497 C>T), RS1001850126 (5:10242626 A>C,T), RS1001977305 (5:10247723 C>T), RS1002023995 (5:10237243 G>A)

Disease associations

OMIM: gene MIM:618568 | 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
GCST001668_1	Pain	5.000000e-07
GCST005184_3	Common carotid intima-media thickness in HIV infection	4.000000e-06
GCST007676_9	3-month functional outcome in ischaemic stroke (modified Rankin score)	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
GSK-J4	decreases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Hydrogen Peroxide	affects expression	1
Niclosamide	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SM86	HAP1 FAM173B (-) 1	Cancer cell line	Male
CVCL_SM87	HAP1 FAM173B (-) 2	Cancer cell line	Male
CVCL_SM88	HAP1 FAM173B (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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