ETNK2

Summary

ETNK2 (ethanolamine kinase 2, HGNC:25575) is a protein-coding gene on chromosome 1q32.1, encoding Ethanolamine kinase 2 (Q9NVF9). Highly specific for ethanolamine phosphorylation.

The protein encoded by this gene is a member of choline/ethanolamine kinase family which catalyzes the first step of phosphatidylethanolamine (PtdEtn) biosynthesis via the cytidine diphosphate (CDP) ethanolamine pathway. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55224 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 53 total — 1 pathogenic
• MANE Select transcript: NM_018208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25575
Approved symbol	ETNK2
Name	ethanolamine kinase 2
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10761, EKI2
Ensembl gene	ENSG00000143845
Ensembl biotype	protein_coding
OMIM	609859
Entrez	55224

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000367197, ENST00000367201, ENST00000367202, ENST00000422072, ENST00000422699, ENST00000429525, ENST00000444817, ENST00000452983, ENST00000472340, ENST00000477125, ENST00000492392

RefSeq mRNA: 4 — MANE Select: NM_018208 NM_001297760, NM_001297761, NM_001297762, NM_018208

CCDS: CCDS1442, CCDS73006

Canonical transcript exons

ENST00000367202 — 8 exons

Exon	Start	End
ENSE00001943286	204151595	204152044
ENSE00002258782	204149703	204149962
ENSE00003459703	204146642	204146764
ENSE00003522467	204131062	204132256
ENSE00003567854	204141315	204141457
ENSE00003665611	204137104	204137249
ENSE00003672675	204134515	204134588
ENSE00003684636	204140035	204140118

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7816 / max 179.5318, expressed in 1273 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16871	1.4008	752
16872	1.2121	602
16868	0.5701	379
16870	0.5148	234
16867	0.4928	305
16869	0.4916	312
16873	0.3037	153
16863	0.2728	71
16866	0.1290	56
16865	0.1251	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.16	gold quality
left testis	UBERON:0004533	97.97	gold quality
right lobe of liver	UBERON:0001114	96.80	gold quality
testis	UBERON:0000473	95.60	gold quality
adult mammalian kidney	UBERON:0000082	93.06	gold quality
liver	UBERON:0002107	92.60	gold quality
adrenal tissue	UBERON:0018303	91.15	gold quality
sperm	CL:0000019	90.94	gold quality
lower esophagus mucosa	UBERON:0035834	89.76	gold quality
male germ cell	CL:0000015	89.61	gold quality
popliteal artery	UBERON:0002250	89.08	gold quality
tibial artery	UBERON:0007610	89.05	gold quality
islet of Langerhans	UBERON:0000006	88.47	gold quality
right ovary	UBERON:0002118	87.82	gold quality
left ovary	UBERON:0002119	87.34	gold quality
aorta	UBERON:0000947	87.27	gold quality
adenohypophysis	UBERON:0002196	87.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.53	gold quality
metanephros cortex	UBERON:0010533	86.26	gold quality
pituitary gland	UBERON:0000007	86.04	gold quality
descending thoracic aorta	UBERON:0002345	85.88	gold quality
ectocervix	UBERON:0012249	85.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.51	gold quality
thoracic aorta	UBERON:0001515	85.33	gold quality
ascending aorta	UBERON:0001496	85.18	gold quality
left coronary artery	UBERON:0001626	85.12	gold quality
cortical plate	UBERON:0005343	84.97	gold quality
tibial nerve	UBERON:0001323	84.90	gold quality
kidney	UBERON:0002113	84.78	gold quality
skin of leg	UBERON:0001511	84.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

50 targeting ETNK2, 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-6798-5P	100.00	65.77	699
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4292	99.16	65.57	1767

Literature-anchored findings (GeneRIF, showing 1)

• Hepatic metastasis of gastric cancer is associated with enhanced expression of ethanolamine kinase 2 via the p53-Bcl-2 intrinsic apoptosis pathway. (PMID:33531692)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	etnk2	ENSDARG00000070213
mus_musculus	Etnk2	ENSMUSG00000070644
rattus_norvegicus	Etnk2	ENSRNOG00000028368
drosophila_melanogaster	eas	FBGN0000536
caenorhabditis_elegans		WBGENE00000515

Paralogs (3): CHKB (ENSG00000100288), CHKA (ENSG00000110721), ETNK1 (ENSG00000139163)

Protein

Protein identifiers

Ethanolamine kinase 2 — Q9NVF9 (reviewed: Q9NVF9)

Alternative names: Ethanolamine kinase-like protein

All UniProt accessions (7): Q9NVF9, B7ZC34, B7ZC35, H0Y771, Q5SXX4, Q5SXX7, Q5SXX8

UniProt curated annotations — full annotation on UniProt →

Function. Highly specific for ethanolamine phosphorylation. Does not have choline kinase activity.

Tissue specificity. Expressed in kidney, liver, ovary, testis and prostate.

Pathway. Phospholipid metabolism; phosphatidylethanolamine biosynthesis; phosphatidylethanolamine from ethanolamine: step 1/3.

Similarity. Belongs to the choline/ethanolamine kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NVF9-1	1	yes
Q9NVF9-2	2
Q9NVF9-3	3

RefSeq proteins (4): NP_001284689, NP_001284690, NP_001284691, NP_060678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011009	Kinase-like_dom_sf	Homologous_superfamily

Pfam: PF01633

Enzyme classification (BRENDA):

• EC 2.7.1.82 — ethanolamine kinase (BRENDA: 27 organisms, 39 substrates, 69 inhibitors, 25 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ETHANOLAMINE	0.008–10	13
ATP	0.0206–10	7
CHOLINE	0.02–0.275	3
DL-1-AMINOPROPAN-2-OL	0.36	1

Catalyzed reactions (Rhea), 1 shown:

• ethanolamine + ATP = phosphoethanolamine + ADP + H(+) (RHEA:13069)

UniProt features (7 total): sequence conflict 3, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVF9-F1	88.55	0.80

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483213	Synthesis of PE

MSigDB gene sets: 100 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, WANG_CLIM2_TARGETS_UP, GOBP_GROWTH, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_MULTICELLULAR_ORGANISM_GROWTH, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, TTGGAGA_MIR5155P_MIR519E

GO Biological Process (7): in utero embryonic development (GO:0001701), placenta development (GO:0001890), phosphatidylethanolamine biosynthetic process (GO:0006646), post-embryonic development (GO:0009791), multicellular organism growth (GO:0035264), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (6): ethanolamine kinase activity (GO:0004305), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	2
cellular anatomical structure	2
chordate embryonic development	1
animal organ development	1
phosphatidylethanolamine metabolic process	1
glycerophospholipid biosynthetic process	1
multicellular organism development	1
developmental growth	1
primary metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ETNK2	PCYT2	Q99447	784
ETNK2	SELENOI	Q9C0D9	733
ETNK2	GOLT1A	Q6ZVE7	690
ETNK2	PISD	Q9UG56	662
ETNK2	CEPT1	Q9Y6K0	645
ETNK2	CHPT1	Q8WUD6	549
ETNK2	PCYT1A	P49585	495
ETNK2	PLEKHA6	Q9Y2H5	477
ETNK2	PCYT1B	Q9Y5K3	452
ETNK2	PEMT	Q9UBM1	449
ETNK2	PTDSS2	Q9BVG9	449
ETNK2	GLYAT	Q6IB77	438
ETNK2	GYS2	P54840	422
ETNK2	PBX4	Q9BYU1	418
ETNK2	PIK3C2B	O00750	415

IntAct

26 interactions, top by confidence:

A	B	Type	Score
CYSRT1	ETNK2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	ETNK2	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	ETNK2	psi-mi:“MI:0915”(physical association)	0.560
STX1A	ETNK2	psi-mi:“MI:0915”(physical association)	0.560
ETNK2	MID2	psi-mi:“MI:0915”(physical association)	0.560
ATN1	ETNK2	psi-mi:“MI:0915”(physical association)	0.560
MDFI	ETNK2	psi-mi:“MI:0915”(physical association)	0.490
ETNK2	RAB11B	psi-mi:“MI:0915”(physical association)	0.400
ETNK1	ETNK2	psi-mi:“MI:0915”(physical association)	0.400
UBE2A	ETNK2	psi-mi:“MI:0915”(physical association)	0.370
NOL3	ETNK2	psi-mi:“MI:0915”(physical association)	0.370
ETNK2	ZNF185	psi-mi:“MI:0914”(association)	0.350
ETNK2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
ETNK2	ATN1	psi-mi:“MI:0915”(physical association)	0.000
ETNK2	KRTAP12-2	psi-mi:“MI:0915”(physical association)	0.000
ETNK2	HNRNPK	psi-mi:“MI:0915”(physical association)	0.000
ETNK2	STX1A	psi-mi:“MI:0915”(physical association)	0.000
ETNK2	MID2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): NPLOC4 (Affinity Capture-MS), RAB11B (Affinity Capture-MS), ETNK2 (Two-hybrid), RAB11B (Affinity Capture-MS), ETNK2 (Two-hybrid), ETNK2 (Two-hybrid), ETNK2 (Two-hybrid), HNRNPK (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP12-2 (Two-hybrid), ETNK2 (Affinity Capture-MS), MAPK3 (Affinity Capture-MS), PUS1 (Affinity Capture-MS), RGP1 (Affinity Capture-MS), DNMBP (Affinity Capture-MS)

ESM2 similar proteins: A2AA28, A2RRH5, A4FV42, A6NDL7, A7MCT6, B0K012, B2RYG8, D3YWP0, D3ZRW8, E1B8U2, J3S6Y1, P21964, P50747, Q0V8R7, Q1JP61, Q2TBI8, Q3SZD4, Q3U2J5, Q4VBE8, Q58DC7, Q5E9Y6, Q5RJL2, Q5VZV1, Q6DJF8, Q6GQ33, Q6P9U1, Q7Z624, Q80WC9, Q86XA0, Q8BNV1, Q8C436, Q8CDZ2, Q8IZ69, Q8N371, Q8R1C6, Q8WU66, Q920N2, Q96AZ1, Q96CB9, Q96RR1

Diamond homologs: A7MCT6, A7SK27, D3ZRW8, O54783, O55229, O81024, P54352, Q869T9, Q8L518, Q9D4V0, Q9HBU6, Q9M9H6, Q9NVF9, Q9SZ92, Q9Y259, P20485, O54804, P35790, P46558, P46559, P46560, Q01134, Q22942, Q554D8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ETNK2	“up-regulates quantity”	O-phosphonatoethanaminium(1-)	“chemical modification”
ETNK2	“down-regulates quantity”	ethanolaminium(1+)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4279354	GRCh37/hg19 1q32.1(chr1:204110068-204144175)x1	Pathogenic

SpliceAI

1295 predictions. Top by Δscore:

Variant	Effect	Δscore
1:204132252:CGTAC:C	acceptor_gain	1.0000
1:204132254:TAC:T	acceptor_gain	1.0000
1:204132254:TACC:T	acceptor_loss	1.0000
1:204132257:C:CC	acceptor_gain	1.0000
1:204134510:CTCA:C	donor_loss	1.0000
1:204134511:TCAC:T	donor_loss	1.0000
1:204134512:CA:C	donor_loss	1.0000
1:204134513:A:AC	donor_gain	1.0000
1:204134513:A:AG	donor_loss	1.0000
1:204134514:C:CC	donor_gain	1.0000
1:204134586:CGC:C	acceptor_gain	1.0000
1:204134589:C:CC	acceptor_gain	1.0000
1:204134589:CT:C	acceptor_loss	1.0000
1:204137100:TCAC:T	donor_loss	1.0000
1:204137101:CAC:C	donor_loss	1.0000
1:204137102:A:AC	donor_gain	1.0000
1:204137103:C:CA	donor_loss	1.0000
1:204137103:C:CC	donor_gain	1.0000
1:204137115:TGTTG:T	donor_gain	1.0000
1:204137145:C:A	donor_gain	1.0000
1:204137245:CACGC:C	acceptor_gain	1.0000
1:204137246:ACGC:A	acceptor_gain	1.0000
1:204137247:CGC:C	acceptor_gain	1.0000
1:204137247:CGCC:C	acceptor_gain	1.0000
1:204137250:C:CC	acceptor_gain	1.0000
1:204137251:T:G	acceptor_loss	1.0000
1:204140029:TCTCA:T	donor_loss	1.0000
1:204140030:CTCAC:C	donor_loss	1.0000
1:204140031:TCACC:T	donor_loss	1.0000
1:204140032:CA:C	donor_loss	1.0000

AlphaMissense

2541 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:204134564:A:G	W347R	0.999
1:204134564:A:T	W347R	0.999
1:204140094:T:A	E270V	0.999
1:204140099:G:C	D268E	0.999
1:204140099:G:T	D268E	0.999
1:204140100:T:A	D268V	0.999
1:204140100:T:G	D268A	0.999
1:204141337:A:C	N254K	0.999
1:204141337:A:T	N254K	0.999
1:204141352:G:C	D249E	0.999
1:204141352:G:T	D249E	0.999
1:204141353:T:A	D249V	0.999
1:204141353:T:C	D249G	0.999
1:204141353:T:G	D249A	0.999
1:204141361:A:C	C246W	0.999
1:204141362:C:T	C246Y	0.999
1:204149772:C:T	G150E	0.999
1:204149780:G:C	F147L	0.999
1:204149780:G:T	F147L	0.999
1:204149782:A:G	F147L	0.999
1:204134520:G:C	F361L	0.998
1:204134520:G:T	F361L	0.998
1:204134522:A:G	F361L	0.998
1:204134526:A:C	F359L	0.998
1:204134526:A:T	F359L	0.998
1:204134528:A:G	F359L	0.998
1:204140078:G:C	N275K	0.998
1:204140078:G:T	N275K	0.998
1:204140101:C:G	D268H	0.998
1:204141338:T:A	N254I	0.998

dbSNP variants (sampled 300 via entrez): RS1000148483 (1:204145317 G>A), RS1000284345 (1:204134595 A>G), RS1000302883 (1:204148744 T>A), RS1000394921 (1:204149910 T>C), RS1000752131 (1:204143622 G>A), RS1000816405 (1:204142340 C>A), RS1001010608 (1:204130673 G>C), RS1001097975 (1:204143291 C>T), RS1001107400 (1:204142359 C>T), RS1001281648 (1:204141717 T>A,C), RS1001338253 (1:204136419 A>G), RS1001410785 (1:204148986 G>A,T), RS1001438950 (1:204135350 A>G), RS1001467448 (1:204134208 C>T), RS1001762417 (1:204140615 C>T)

Disease associations

OMIM: gene MIM:609859 | 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
GCST000924_4	Response to acetaminophen (hepatotoxicity)	7.000000e-06
GCST002126_28	Periodontitis (CDC/AAP)	5.000000e-06
GCST008359_1	Response to cognitive-behavioural therapy in anxiety disorder	7.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
Particulate Matter	decreases expression, increases abundance, increases expression, increases methylation	3
bisphenol S	decreases expression, decreases methylation	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Valproic Acid	increases expression	2
bisphenol F	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
propylparaben	decreases expression	1
lead acetate	decreases expression	1
methylparaben	decreases expression	1
o,p’-DDT	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
cupric chloride	decreases expression	1
pentanal	increases expression	1
ICG 001	decreases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Calcitriol	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1

Clinical trials (associated diseases)

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