ENOPH1

Summary

ENOPH1 (enolase-phosphatase 1, HGNC:24599) is a protein-coding gene on chromosome 4q21.22, encoding Enolase-phosphatase E1 (Q9UHY7). Bifunctional enzyme that catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK-MTPenyl-1-P), which is then dephosphorylated to form the acireductone 1,2-dihydroxy-3-keto-5-m….

Enables acireductone synthase activity. Involved in L-methionine salvage from methylthioadenosine. Predicted to be located in cytosol.

Source: NCBI Gene 58478 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_021204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24599
Approved symbol	ENOPH1
Name	enolase-phosphatase 1
Location	4q21.22
Locus type	gene with protein product
Status	Approved
Aliases	MASA, E1, mtnC
Ensembl gene	ENSG00000145293
Ensembl biotype	protein_coding
Entrez	58478

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000273920, ENST00000505846, ENST00000509635, ENST00000855199, ENST00000965409

RefSeq mRNA: 2 — MANE Select: NM_021204 NM_001292017, NM_021204

CCDS: CCDS3594, CCDS75154

Canonical transcript exons

ENST00000273920 — 6 exons

Exon	Start	End
ENSE00001150347	82459981	82461177
ENSE00001296627	82430590	82430913
ENSE00001385975	82456915	82457038
ENSE00003559046	82454722	82454854
ENSE00003588194	82451043	82451245
ENSE00003617408	82447920	82448021

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.5483 / max 274.1436, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48582	40.7947	1818
48584	1.4562	909
48583	1.1651	801
48581	0.1324	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.17	gold quality
inferior olivary complex	UBERON:0002127	98.12	gold quality
spinal cord	UBERON:0002240	98.03	gold quality
secondary oocyte	CL:0000655	97.87	gold quality
pons	UBERON:0000988	97.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.82	gold quality
subthalamic nucleus	UBERON:0001906	97.80	gold quality
lateral globus pallidus	UBERON:0002476	97.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.49	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.46	gold quality
cortical plate	UBERON:0005343	97.35	gold quality
substantia nigra pars compacta	UBERON:0001965	97.29	gold quality
inferior vagus X ganglion	UBERON:0005363	97.16	gold quality
medulla oblongata	UBERON:0001896	97.10	gold quality
substantia nigra	UBERON:0002038	97.09	gold quality
midbrain	UBERON:0001891	97.00	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.93	gold quality
corpus callosum	UBERON:0002336	96.91	gold quality
amygdala	UBERON:0001876	96.80	gold quality
superior vestibular nucleus	UBERON:0007227	96.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.67	gold quality
cranial nerve II	UBERON:0000941	96.64	gold quality
prefrontal cortex	UBERON:0000451	96.53	gold quality
anterior cingulate cortex	UBERON:0009835	96.46	gold quality
cingulate cortex	UBERON:0003027	96.45	gold quality
hypothalamus	UBERON:0001898	96.43	gold quality
pigmented layer of retina	UBERON:0001782	96.32	gold quality
Ammon’s horn	UBERON:0001954	96.32	gold quality
retina	UBERON:0000966	96.30	gold quality
ventricular zone	UBERON:0003053	96.25	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

miRNA regulators (miRDB)

76 targeting ENOPH1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-181B-2-3P	99.81	70.06	1646

Literature-anchored findings (GeneRIF, showing 5)

• the crystal structure of MASA and its complex with a substrate analog (PMID:15843022)
• High ENOPH1 expression is associated with malignant glioma. (PMID:30066900)
• Taken together, these findings illustrate that ENOPH1 promotes hepatocellular carcinoma progression. (PMID:31281503)
• Enolase-phosphatase 1 acts as an oncogenic driver in glioma. (PMID:32654229)
• Tumor-promoting properties of enolase-phosphatase 1 in breast cancer via activating the NF-kappaB signaling pathway. (PMID:36378417)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	enoph1	ENSDARG00000026198
mus_musculus	Enoph1	ENSMUSG00000029326
rattus_norvegicus	Enoph1	ENSRNOG00000002262
drosophila_melanogaster	Enoph	FBGN0037305
caenorhabditis_elegans		WBGENE00010286

Protein

Protein identifiers

Enolase-phosphatase E1 — Q9UHY7 (reviewed: Q9UHY7)

Alternative names: 2,3-diketo-5-methylthio-1-phosphopentane phosphatase, MASA homolog

All UniProt accessions (2): Q9UHY7, D6RA00

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme that catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK-MTPenyl-1-P), which is then dephosphorylated to form the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene).

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Nucleus.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Pathway. Amino-acid biosynthesis; L-methionine biosynthesis via salvage pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate: step 3/6. Amino-acid biosynthesis; L-methionine biosynthesis via salvage pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate: step 4/6.

Similarity. Belongs to the HAD-like hydrolase superfamily. MasA/MtnC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UHY7-1	1	yes
Q9UHY7-2	2

RefSeq proteins (2): NP_001278946, NP_067027* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006439	HAD-SF_hydro_IA	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR023943	Enolase-ppase_E1	Family
IPR027511	ENOPH1_eukaryotes	Family
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF00702

Enzyme classification (BRENDA):

• EC 3.1.3.77 — acireductone synthase (BRENDA: 5 organisms, 3 substrates, 0 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2,3-DIKETO-1-PHOSPHOHEXANE	0.077	1
2-HYDROXY-3-KETO-1-PHOSPHO-1-HEXENE	0.0071	1

Catalyzed reactions (Rhea), 1 shown:

• 5-methylsulfanyl-2,3-dioxopentyl phosphate + H2O = 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one + phosphate (RHEA:21700)

UniProt features (29 total): helix 14, strand 6, binding site 5, turn 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1YNS	X-RAY DIFFRACTION	1.7
1ZS9	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHY7-F1	95.62	0.94

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 (5): 16; 18; 153–154; 187; 212

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1237112	Methionine salvage pathway

MSigDB gene sets: 141 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ASPARTATE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_METHIONINE_BIOSYNTHETIC_PROCESS, GOBP_METHIONINE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, GOBP_SULFUR_AMINO_ACID_METABOLIC_PROCESS

GO Biological Process (3): obsolete L-methionine salvage from methylthioadenosine (GO:0019509), amino acid biosynthetic process (GO:0008652), obsolete methionine biosynthetic process (GO:0009086)

GO Molecular Function (5): magnesium ion binding (GO:0000287), acireductone synthase activity (GO:0043874), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Sulfur amino acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
amino acid metabolic process	1
biosynthetic process	1
metal ion binding	1
phosphatase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1017 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENOPH1	ADI1	Q9BV57	811
ENOPH1	MRI1	Q9BV20	808
ENOPH1	APIP	Q96GX9	715
ENOPH1	MTAP	Q13126	589
ENOPH1	BHMT2	Q9H2M3	524
ENOPH1	RASGEF1B	Q0VAM2	505
ENOPH1	SRM	P19623	494
ENOPH1	PRKG2	Q13237	418
ENOPH1	ODC1	P11926	412
ENOPH1	L2HGDH	Q9H9P8	408
ENOPH1	SHMT2	P34897	405
ENOPH1	MAT2A	P31153	400
ENOPH1	ZSCAN29	Q8IWY8	400
ENOPH1	FAM20C	Q8IXL6	399
ENOPH1	BHMT	Q93088	395

IntAct

30 interactions, top by confidence:

A	B	Type	Score
RNF41	ENOPH1	psi-mi:“MI:0915”(physical association)	0.740
ZNF280A	ENOPH1	psi-mi:“MI:0915”(physical association)	0.560
ENOPH1	RPS27	psi-mi:“MI:0915”(physical association)	0.550
ENOPH1	THEM4	psi-mi:“MI:0914”(association)	0.530
ENOPH1	VPS52	psi-mi:“MI:0914”(association)	0.530
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
ERBB3	ENOPH1	psi-mi:“MI:0915”(physical association)	0.370
ENOPH1	RAB10	psi-mi:“MI:0915”(physical association)	0.370
TMEM132A	WWP2	psi-mi:“MI:0914”(association)	0.350
TGM2	SRGAP3	psi-mi:“MI:0914”(association)	0.350
MYO19	ITGB4	psi-mi:“MI:0914”(association)	0.350
BAG3	HTT	psi-mi:“MI:0914”(association)	0.350
Syce2	DNAJA2	psi-mi:“MI:0914”(association)	0.350
BAG6	CNOT1	psi-mi:“MI:0914”(association)	0.350
TMEM63B	CAV1	psi-mi:“MI:0914”(association)	0.350
KATNA1	KATNBL1	psi-mi:“MI:0914”(association)	0.350
ENOPH1	ACTA2	psi-mi:“MI:0914”(association)	0.350
ENOPH1	RNF41	psi-mi:“MI:0915”(physical association)	0.000
ENOPH1	ZNF280A	psi-mi:“MI:0915”(physical association)	0.000
RNF41	ENOPH1	psi-mi:“MI:0915”(physical association)	0.000
RPS27	ENOPH1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): ENOPH1 (Affinity Capture-RNA), CBS (Co-fractionation), ENOPH1 (Co-fractionation), ENOPH1 (Co-fractionation), ENOPH1 (Co-fractionation), ENOPH1 (Co-fractionation), ENOPH1 (Co-fractionation), HDHD1 (Co-fractionation), IMPDH2 (Co-fractionation), MANF (Co-fractionation), PRDX6 (Co-fractionation), SNX2 (Co-fractionation), ENOPH1 (Affinity Capture-MS), ENOPH1 (Affinity Capture-MS), ENOPH1 (Affinity Capture-MS)

ESM2 similar proteins: A2A825, A2VE14, A9CQL8, D3ZVR7, P28801, P47802, Q0VCJ8, Q0VD18, Q0VD27, Q27HK4, Q29RZ1, Q2TBS1, Q3SZB3, Q3U129, Q4R3I0, Q58CY6, Q5H8A4, Q5I0D5, Q5NVN7, Q5R7S9, Q5R8R5, Q5RAJ8, Q5VYX0, Q5ZIL9, Q5ZJB7, Q5ZMH6, Q67FW5, Q6AXQ0, Q6GV29, Q7RTV5, Q86XA0, Q86XW9, Q8BGB7, Q8N8L6, Q8NB37, Q8TBF2, Q91YQ7, Q96G75, Q96MZ0, Q9BU20

Diamond homologs: A0KRB5, A1JP11, A1RQ67, A1S1N0, A1TZ36, A2CBQ3, A3DAG6, A3QJI9, A4TPN1, A4W7Z3, A4Y1H2, A5FUG6, A5GJ48, A5GR42, A6T673, A6V7A6, A6WHG9, A7FLL3, A7MK11, A8ANI1, A8G1T3, A8GAA9, A8HAA3, A8Y461, A9FCY5, A9KV69, A9R2Z7, A9RBS1, B0SFG5, B0SP16, B0TM50, B0U3A6, B1JIK5, B1KPZ1, B1XPT1, B2I5X4, B2K631, B2SM84, B2V7G7, B2VIR2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

834 predictions. Top by Δscore:

Variant	Effect	Δscore
4:82447906:A:AG	acceptor_gain	1.0000
4:82447907:C:G	acceptor_gain	1.0000
4:82447914:A:AG	acceptor_gain	1.0000
4:82447916:CCA:C	acceptor_loss	1.0000
4:82447917:CA:C	acceptor_loss	1.0000
4:82447918:A:AC	acceptor_loss	1.0000
4:82447918:A:AG	acceptor_gain	1.0000
4:82447918:AG:A	acceptor_gain	1.0000
4:82447919:G:A	acceptor_loss	1.0000
4:82447919:G:GT	acceptor_gain	1.0000
4:82447919:GG:G	acceptor_gain	1.0000
4:82447919:GGA:G	acceptor_gain	1.0000
4:82447919:GGAC:G	acceptor_gain	1.0000
4:82447919:GGACA:G	acceptor_gain	1.0000
4:82447997:GGAT:G	donor_gain	1.0000
4:82447998:GATG:G	donor_gain	1.0000
4:82448015:G:GT	donor_gain	1.0000
4:82448016:A:T	donor_gain	1.0000
4:82448020:AGG:A	donor_loss	1.0000
4:82448021:GG:G	donor_loss	1.0000
4:82448022:GTTGG:G	donor_loss	1.0000
4:82451033:T:A	acceptor_gain	1.0000
4:82451038:TAAA:T	acceptor_loss	1.0000
4:82451041:AGG:A	acceptor_loss	1.0000
4:82451042:G:GA	acceptor_loss	1.0000
4:82451227:C:G	donor_gain	1.0000
4:82451241:GCAGA:G	donor_gain	1.0000
4:82451244:GA:G	donor_gain	1.0000
4:82451246:G:GG	donor_gain	1.0000
4:82454720:A:AG	acceptor_gain	1.0000

AlphaMissense

1710 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:82456953:A:C	K187N	0.998
4:82456953:A:T	K187N	0.998
4:82451189:A:C	K111N	0.997
4:82451189:A:T	K111N	0.997
4:82454812:G:C	Q160H	0.997
4:82454812:G:T	Q160H	0.997
4:82456952:A:T	K187I	0.997
4:82460029:G:C	R232T	0.997
4:82430876:A:T	D16V	0.996
4:82430884:G:C	G19R	0.996
4:82456930:T:C	F180L	0.996
4:82456932:T:A	F180L	0.996
4:82456932:T:G	F180L	0.996
4:82451188:A:T	K111I	0.995
4:82457017:T:C	F209L	0.995
4:82457019:T:A	F209L	0.995
4:82457019:T:G	F209L	0.995
4:82460030:A:C	R232S	0.995
4:82460030:A:T	R232S	0.995
4:82430877:T:A	D16E	0.994
4:82430877:T:G	D16E	0.994
4:82456966:A:C	S192R	0.994
4:82456968:T:A	S192R	0.994
4:82456968:T:G	S192R	0.994
4:82457024:C:T	T211I	0.994
4:82430876:A:C	D16A	0.993
4:82430883:A:C	E18D	0.993
4:82430883:A:T	E18D	0.993
4:82430884:G:T	G19C	0.993
4:82451174:G:C	K106N	0.993

dbSNP variants (sampled 300 via entrez): RS1000102077 (4:82433770 G>A), RS1000134171 (4:82443584 C>G,T), RS1000214211 (4:82443948 T>C), RS10002169 (4:82429944 G>A,C), RS1000341381 (4:82449513 A>G), RS1000394374 (4:82446529 A>G), RS1000491471 (4:82458396 A>G,T), RS1000705311 (4:82452297 C>A), RS1000730376 (4:82444882 G>A), RS1000777139 (4:82454219 A>C), RS1000840435 (4:82428953 G>A), RS1000884860 (4:82461641 C>G), RS1000914202 (4:82437224 T>C), RS1001081339 (4:82448464 A>G), RS1001115683 (4:82431165 C>A,G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
Sunitinib	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Gallic Acid	increases expression	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation, increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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