HYI

Summary

HYI (hydroxypyruvate isomerase (putative), HGNC:26948) is a protein-coding gene on chromosome 1p34.2, encoding Putative hydroxypyruvate isomerase (Q5T013). Catalyzes the reversible isomerization between hydroxypyruvate and 2-hydroxy-3-oxopropanoate (also termed tartronate semialdehyde).

This gene encodes a putative hydroxypyruvate isomerase, which likely catalyzes the conversion of hydroxypyruvate to 2-hydroxy-3-oxopropanoate, and may be involved in carbohydrate transport and metabolism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 81888 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001190880

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26948
Approved symbol	HYI
Name	hydroxypyruvate isomerase (putative)
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	HT036
Ensembl gene	ENSG00000178922
Ensembl biotype	protein_coding
OMIM	619128
Entrez	81888

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 4 retained_intron

ENST00000372427, ENST00000372430, ENST00000372432, ENST00000372433, ENST00000372434, ENST00000469587, ENST00000470662, ENST00000483618, ENST00000486909, ENST00000487366, ENST00000496142, ENST00000583037, ENST00000895723, ENST00000895724, ENST00000895725, ENST00000895726, ENST00000895727, ENST00000895728, ENST00000895729, ENST00000895730, ENST00000895731, ENST00000965724

RefSeq mRNA: 4 — MANE Select: NM_001190880 NM_001190880, NM_001243526, NM_001330526, NM_031207

CCDS: CCDS488, CCDS53309, CCDS72771, CCDS81313

Canonical transcript exons

ENST00000372430 — 8 exons

Exon	Start	End
ENSE00001248838	43451410	43451544
ENSE00001248859	43452205	43452319
ENSE00001552749	43453595	43453931
ENSE00003469400	43451935	43452013
ENSE00003527548	43451648	43451717
ENSE00003557709	43451798	43451847
ENSE00003668431	43453386	43453497
ENSE00003910972	43450989	43451311

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 97.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.3026 / max 368.8689, expressed in 1718 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12050	21.9721	1685
12049	5.9704	1469
12048	0.1927	114
12051	0.0658	25
12046	0.0508	36
12047	0.0508	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.19	gold quality
right lobe of liver	UBERON:0001114	96.04	gold quality
left ovary	UBERON:0002119	95.95	gold quality
tendon of biceps brachii	UBERON:0008188	95.83	gold quality
right ovary	UBERON:0002118	95.55	gold quality
endocervix	UBERON:0000458	95.35	gold quality
mucosa of transverse colon	UBERON:0004991	95.29	gold quality
body of uterus	UBERON:0009853	95.17	gold quality
mucosa of stomach	UBERON:0001199	94.97	gold quality
left uterine tube	UBERON:0001303	94.85	gold quality
left coronary artery	UBERON:0001626	94.60	gold quality
tibial artery	UBERON:0007610	94.60	gold quality
popliteal artery	UBERON:0002250	94.59	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.59	gold quality
body of stomach	UBERON:0001161	94.50	gold quality
right coronary artery	UBERON:0001625	94.50	gold quality
descending thoracic aorta	UBERON:0002345	94.50	gold quality
transverse colon	UBERON:0001157	94.48	gold quality
ascending aorta	UBERON:0001496	94.48	gold quality
thoracic aorta	UBERON:0001515	94.48	gold quality
aorta	UBERON:0000947	94.46	gold quality
stromal cell of endometrium	CL:0002255	94.32	gold quality
adenohypophysis	UBERON:0002196	94.26	gold quality
left lobe of thyroid gland	UBERON:0001120	94.20	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.14	gold quality
coronary artery	UBERON:0001621	94.12	gold quality
right lobe of thyroid gland	UBERON:0001119	94.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.75	gold quality
metanephros cortex	UBERON:0010533	93.67	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting HYI, 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-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-4669	97.94	62.71	224
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-1293	96.16	64.69	916

Literature-anchored findings (GeneRIF, showing 1)

• Protein HYI may closely bind with protein P311 by an alpha helix in hypertrophic scar fibroblasts. (PMID:22490543)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hyi	ENSDARG00000030166
rattus_norvegicus	Hyi	ENSRNOG00000037518
drosophila_melanogaster	Gip	FBGN0011770
caenorhabditis_elegans		WBGENE00015483

Protein

Protein identifiers

Putative hydroxypyruvate isomerase — Q5T013 (reviewed: Q5T013)

Alternative names: Endothelial cell apoptosis protein E-CE1

All UniProt accessions (8): A0A0A0MTR5, E7EWH8, Q5T013, F6UJY1, F6UJY9, H0YB18, H0YB70, J9JIE9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible isomerization between hydroxypyruvate and 2-hydroxy-3-oxopropanoate (also termed tartronate semialdehyde).

Induction. Up-regulated by exposure to 7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) after which is found in the culture medium of amniotic epithelial cells.

Similarity. Belongs to the hyi family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5T013-1	1	yes
Q5T013-2	2
Q5T013-3	3
Q5T013-4	4

RefSeq proteins (4): NP_001177809, NP_001230455, NP_001317455, NP_112484 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013022	Xyl_isomerase-like_TIM-brl	Domain
IPR026040	HyI-like	Family
IPR036237	Xyl_isomerase-like_sf	Homologous_superfamily
IPR050417	Sugar_Epim/Isomerase	Family

Pfam: PF01261

Catalyzed reactions (Rhea), 1 shown:

• 3-hydroxypyruvate = 2-hydroxy-3-oxopropanoate (RHEA:11952)

UniProt features (8 total): active site 2, splice variant 2, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T013-F1	96.41	0.97

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 (2): 150 (proton donor/acceptor); 249 (proton donor/acceptor)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_GLYOXYLATE_METABOLIC_PROCESS, chr1p34, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_ALDEHYDE_METABOLIC_PROCESS, MODULE_88, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, MODULE_60, MODULE_55, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, GOMF_ISOMERASE_ACTIVITY, GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY_INTERCONVERTING_ALDOSES_AND_KETOSES, MEISSNER_NPC_HCP_WITH_H3K4ME2

GO Biological Process (1): glyoxylate metabolic process (GO:0046487)

GO Molecular Function (3): hydroxypyruvate isomerase activity (GO:0008903), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aldehyde metabolic process	1
monocarboxylic acid metabolic process	1
intramolecular oxidoreductase activity, interconverting aldoses and ketoses	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HYI	GLYCTK	Q8IVS8	530
HYI	PARP3	Q9Y6F1	490
HYI	GRHPR	Q9UBQ7	463
HYI	PARP6	Q2NL67	422
HYI	PARP16	Q8N5Y8	413
HYI	TRPT1	Q86TN4	411
HYI	PARP15	Q460N3	406
HYI	CRLF3	Q8IUI8	393
HYI	PARP9	Q8IXQ6	373
HYI	PARP12	Q9H0J9	371
HYI	PARP8	Q8N3A8	365
HYI	MTG2	Q9H4K7	365
HYI	SKA1	Q96BD8	357
HYI	DOHH	Q9BU89	349
HYI	DHX34	Q14147	343

IntAct

11 interactions, top by confidence:

A	B	Type	Score
HYI	TEX11	psi-mi:“MI:0915”(physical association)	0.670
TEX11	HYI	psi-mi:“MI:0915”(physical association)	0.670
SRSF11	HYI	psi-mi:“MI:0915”(physical association)	0.560
HYI	SRSF11	psi-mi:“MI:0915”(physical association)	0.560
HYI	DDAH2	psi-mi:“MI:0915”(physical association)	0.500
HYI	DDAH2	psi-mi:“MI:0914”(association)	0.500
TFAP2A	HYI	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (31): HYI (Two-hybrid), HYI (Two-hybrid), HYI (Two-hybrid), ACY1 (Co-fractionation), HSPA9 (Co-fractionation), HYI (Co-fractionation), HYI (Co-fractionation), HYI (Co-fractionation), PDXK (Co-fractionation), HYI (Affinity Capture-MS), HYI (Affinity Capture-MS), HYI (Affinity Capture-MS), HYI (Two-hybrid), HYI (Two-hybrid), HYI (Two-hybrid)

ESM2 similar proteins: A0A172U6X0, A0A1L7NQ96, A1JSK6, A1KUB4, A3QF58, A4IPB5, A6THJ4, A7ZAH3, A7ZAH7, A9CH28, A9EVN4, A9M4C4, A9N563, B2VJP2, B3R1A0, B3W8L5, B5F3F3, B5Y2S3, B8I944, O50580, P30147, P36951, P42416, P42419, P42972, P45541, P54724, P73599, P76044, Q0KBD1, Q0VPD2, Q11185, Q2Y5Y2, Q44015, Q46891, Q57151, Q5F5H9, Q5T013, Q5WKY7, Q65D04

Diamond homologs: P30147, P36951, Q0KBD1, Q11185, Q44015, Q46891, Q57151, Q5T013, Q63B72, Q6CZ23, Q6NUD4, Q7T3H9, Q8R1F5, Q9Z596, C1KKR1, Q9X8H0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1667 predictions. Top by Δscore:

Variant	Effect	Δscore
1:43451427:CAG:C	donor_gain	1.0000
1:43451465:T:TC	acceptor_gain	1.0000
1:43451543:CC:C	acceptor_gain	1.0000
1:43451544:CC:C	acceptor_gain	1.0000
1:43451793:CTTA:C	donor_loss	1.0000
1:43451794:TTAC:T	donor_loss	1.0000
1:43451795:TACCA:T	donor_loss	1.0000
1:43451796:A:AT	donor_loss	1.0000
1:43451797:C:CT	donor_loss	1.0000
1:43451843:TGCCG:T	acceptor_gain	1.0000
1:43451844:GCCG:G	acceptor_gain	1.0000
1:43451845:CCG:C	acceptor_gain	1.0000
1:43451845:CCGC:C	acceptor_gain	1.0000
1:43451846:CG:C	acceptor_gain	1.0000
1:43451846:CGC:C	acceptor_gain	1.0000
1:43451847:GCTG:G	acceptor_loss	1.0000
1:43451848:C:CC	acceptor_gain	1.0000
1:43451849:T:A	acceptor_loss	1.0000
1:43451933:AC:A	donor_gain	1.0000
1:43451934:CC:C	donor_gain	1.0000
1:43451426:A:AC	donor_gain	0.9900
1:43451426:ACAG:A	donor_gain	0.9900
1:43451426:ACAGC:A	donor_gain	0.9900
1:43451427:C:CC	donor_gain	0.9900
1:43451427:CAGC:C	donor_gain	0.9900
1:43451427:CAGCC:C	donor_gain	0.9900
1:43451460:A:T	acceptor_gain	0.9900
1:43451462:CAGT:C	acceptor_gain	0.9900
1:43451463:A:T	acceptor_gain	0.9900
1:43451465:T:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000646282 (1:43453963 G>A,T), RS1002605123 (1:43452450 C>T), RS1002975255 (1:43453446 G>A), RS1003060751 (1:43455515 A>G), RS1004344032 (1:43453537 C>A,G,T), RS1005398516 (1:43454527 C>A), RS1005757323 (1:43454184 A>G), RS1006219281 (1:43450735 G>A,T), RS1006352210 (1:43455748 C>A,T), RS1007412211 (1:43455381 C>G), RS1008634653 (1:43454721 G>A), RS1008698980 (1:43453745 G>A,C), RS1009186561 (1:43455001 T>A), RS1009236200 (1:43453977 A>G), RS1009996160 (1:43453228 A>T)

Disease associations

OMIM: gene MIM:619128 | disease phenotypes: MIM:615476

GenCC curated gene-disease

Mondo (1): developmental and epileptic encephalopathy, 18 (MONDO:0014201)

Orphanet (1): OBSOLETE: Early infantile epileptic encephalopathy without suppression burst (Orphanet:369894)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST009600_66	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-08
GCST010696_6	Cortical thickness (min-P)	3.000000e-08
GCST010697_32	Cortical surface area (min-P)	4.000000e-08
GCST010698_63	Subcortical volume (min-P)	3.000000e-09
GCST010699_87	Brain morphology (min-P)	9.000000e-14
GCST010700_24	Cortical thickness (MOSTest)	1.000000e-10
GCST010701_5	Cortical surface area (MOSTest)	1.000000e-08
GCST010702_132	Subcortical volume (MOSTest)	8.000000e-15
GCST010703_201	Brain morphology (MOSTest)	1.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	6
Nickel	decreases expression	2
Smoke	increases abundance, increases expression	2
TAK-243	increases sumoylation	1
arsenite	increases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
CGP 52608	increases reaction, affects binding	1
belinostat	decreases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lead	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Phenobarbital	affects expression	1
Rotenone	increases expression	1
Silicon Dioxide	increases expression	1
T-2 Toxin	increases expression	1
Vanadates	increases expression	1
Cyclosporine	decreases methylation	1
Antirheumatic Agents	increases expression	1
Genistein	decreases expression	1

Clinical trials (associated diseases)

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