GLOD4

Summary

GLOD4 (glyoxalase domain containing 4, HGNC:14111) is a protein-coding gene on chromosome 17p13.3, encoding Glyoxalase domain-containing protein 4 (Q9HC38).

Enables cadherin binding activity. Located in extracellular exosome and mitochondrion.

Source: NCBI Gene 51031 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 77 total
• Druggable target: yes
• MANE Select transcript: NM_016080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14111
Approved symbol	GLOD4
Name	glyoxalase domain containing 4
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-150, HC71
Ensembl gene	ENSG00000167699
Ensembl biotype	protein_coding
OMIM	620650
Entrez	51031

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 14 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000301328, ENST00000301329, ENST00000571073, ENST00000572220, ENST00000573137, ENST00000574354, ENST00000574554, ENST00000574581, ENST00000575528, ENST00000575790, ENST00000575800, ENST00000575851, ENST00000576239, ENST00000576419, ENST00000576670, ENST00000576750, ENST00000625892, ENST00000628529, ENST00000891259, ENST00000891260, ENST00000940416, ENST00000940417, ENST00000940418, ENST00000940419, ENST00000940420, ENST00000956992

RefSeq mRNA: 17 — MANE Select: NM_016080 NM_001366247, NM_001366248, NM_001366249, NM_001366250, NM_001389725, NM_001389726, NM_001389727, NM_001389728, NM_001389729, NM_001389730, NM_001389731, NM_001389732, NM_001389733, NM_001389734, NM_001389735, NM_001389736, NM_016080

CCDS: CCDS32520, CCDS92216

Canonical transcript exons

ENST00000301329 — 9 exons

Exon	Start	End
ENSE00002682687	759330	760238
ENSE00003475471	769869	769955
ENSE00003527581	776868	776988
ENSE00003554216	778695	778744
ENSE00003562753	775775	775919
ENSE00003621589	770044	770157
ENSE00003667084	771325	771461
ENSE00003676274	770421	770507
ENSE00003681646	782166	782280

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.3001 / max 1311.0568, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163643	49.0712	1823
163644	2.2289	1184

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.64	gold quality
ventricular zone	UBERON:0003053	96.62	gold quality
duodenum	UBERON:0002114	96.56	gold quality
cortical plate	UBERON:0005343	96.27	gold quality
islet of Langerhans	UBERON:0000006	96.14	gold quality
rectum	UBERON:0001052	95.89	gold quality
ganglionic eminence	UBERON:0004023	95.87	gold quality
epithelium of nasopharynx	UBERON:0001951	95.26	gold quality
nasopharynx	UBERON:0001728	95.24	gold quality
adrenal tissue	UBERON:0018303	95.07	gold quality
palpebral conjunctiva	UBERON:0001812	95.04	gold quality
mucosa of transverse colon	UBERON:0004991	95.04	gold quality
prefrontal cortex	UBERON:0000451	94.96	gold quality
body of stomach	UBERON:0001161	94.93	gold quality
skin of leg	UBERON:0001511	94.91	gold quality
embryo	UBERON:0000922	94.84	gold quality
skin of abdomen	UBERON:0001416	94.72	gold quality
esophagus squamous epithelium	UBERON:0006920	94.70	gold quality
stomach	UBERON:0000945	94.54	gold quality
calcaneal tendon	UBERON:0003701	94.47	gold quality
gall bladder	UBERON:0002110	94.34	gold quality
ileal mucosa	UBERON:0000331	94.31	gold quality
pancreas	UBERON:0001264	94.18	gold quality
oocyte	CL:0000023	94.12	gold quality
zone of skin	UBERON:0000014	94.07	gold quality
monocyte	CL:0000576	94.03	gold quality
leukocyte	CL:0000738	94.00	gold quality
right adrenal gland cortex	UBERON:0035827	94.00	gold quality
mononuclear cell	CL:0000842	93.99	gold quality
right uterine tube	UBERON:0001302	93.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.08
E-GEOD-110499	no	123.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting GLOD4, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-1285-5P	98.01	68.71	779
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-6791-3P	97.45	64.31	1123

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	glod4	ENSDARG00000042509
mus_musculus	Glod4	ENSMUSG00000017286
drosophila_melanogaster	CG1532	FBGN0031143
caenorhabditis_elegans		WBGENE00006448

Paralogs (1): GLO1 (ENSG00000124767)

Protein

Protein identifiers

Glyoxalase domain-containing protein 4 — Q9HC38 (reviewed: Q9HC38)

All UniProt accessions (10): Q9HC38, I3L1F4, I3L1I0, I3L277, I3L2C2, I3L3G0, I3L3Q4, I3NI24, I3NI27, K7ENF2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with NUDT9.

Subcellular location. Mitochondrion.

Tissue specificity. Expressed in heart, brain, liver, kidney, pancreas and placenta. Not expressed in skeletal muscle and lung.

Miscellaneous. Expression is decreased in hepatocellular carcinoma samples as compared to adjacent non-cancerous liver tissues from the same patients. Transfection in hepatocellular carcinoma cells and overexpression can inhibit the cell growth.

Similarity. Belongs to the glyoxalase I family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HC38-1	1	yes
Q9HC38-2	2
Q9HC38-3	3

RefSeq proteins (17): NP_001353176, NP_001353177, NP_001353178, NP_001353179, NP_001376654, NP_001376655, NP_001376656, NP_001376657, NP_001376658, NP_001376659, NP_001376660, NP_001376661, NP_001376662, NP_001376663, NP_001376664, NP_001376665, NP_057164* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029068	Glyas_Bleomycin-R_OHBP_Dase	Homologous_superfamily
IPR037523	VOC_core	Domain
IPR043193	GLOD4	Family
IPR043194	GLOD4_C	Domain
IPR059155	GLOD4_dom	Domain

Pfam: PF21207, PF21701

UniProt features (34 total): strand 16, helix 6, splice variant 3, domain 2, turn 2, modified residue 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3ZI1	X-RAY DIFFRACTION	1.9
9CSJ	X-RAY DIFFRACTION	2.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC38-F1	89.78	0.75

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 (2): 146, 288

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 155 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, BROWNE_HCMV_INFECTION_6HR_DN, MORF_SKP1A, BROWNE_HCMV_INFECTION_14HR_DN, E4F1_Q6, MORF_PPP6C, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, LE_EGR2_TARGETS_DN, CREBP1CJUN_01, ZHONG_SECRETOME_OF_LUNG_CANCER_AND_FIBROBLAST, CREB_01, BLALOCK_ALZHEIMERS_DISEASE_DN, TGACGTCA_ATF3_Q6, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN

GO Biological Process (0):

GO Molecular Function (1): cadherin binding (GO:0045296)

GO Cellular Component (2): mitochondrion (GO:0005739), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell adhesion molecule binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

2986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLOD4	LRRC66	Q68CR7	530
GLOD4	GLO1	P78375	480
GLOD4	CCDC60	Q8IWA6	476
GLOD4	PARK7	Q99497	455
GLOD4	HPDL	Q96IR7	448
GLOD4	SPATA4	Q8NEY3	439
GLOD4	GLOD5	A6NK44	418
GLOD4	FAM32A	Q9Y421	417
GLOD4	GINM1	Q9NU53	412
GLOD4	TPI1	P00938	378
GLOD4	HACL1	Q9UJ83	373
GLOD4	PCDHGB2	Q9Y5G2	370
GLOD4	RIMKLB	Q9ULI2	361
GLOD4	H6PD	O95479	359
GLOD4	RPS20	P17075	352

IntAct

38 interactions, top by confidence:

A	B	Type	Score
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
NECAP2	AP2A2	psi-mi:“MI:0914”(association)	0.530
GLOD4	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
GLOD4		psi-mi:“MI:0915”(physical association)	0.370
GLOD4	BCL2L1	psi-mi:“MI:0915”(physical association)	0.370
NR4A1	GLOD4	psi-mi:“MI:0915”(physical association)	0.370
PNRC2	GLOD4	psi-mi:“MI:0915”(physical association)	0.370
Vav2	CALU	psi-mi:“MI:0914”(association)	0.350
MAX	SND1	psi-mi:“MI:0914”(association)	0.350
	KRAS	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GLOD4	NRG1	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
AZU1	UBA6	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DNAJC30	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
OSBPL11	DNM1L	psi-mi:“MI:0914”(association)	0.350
RBPMS	CA2	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
SCLT1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (108): ALDOC (Co-fractionation), FKBP1B (Co-fractionation), FKBP2 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation), GLOD4 (Co-fractionation)

ESM2 similar proteins: A0A455R7M0, A3KMV5, A4FUZ6, A4IS40, A6NK44, B1HZM2, O04885, O06695, O49818, P0A1Q2, P0A1Q3, P0AC81, P0AC82, P0AC83, P0C5H0, P16635, P22314, P40510, P44638, P46235, P56216, P80064, Q04760, Q17CS8, Q18164, Q28CR0, Q29504, Q39227, Q42891, Q4KLB0, Q4R5F2, Q502D1, Q5I0D1, Q66KC4, Q6CDR5, Q6P5L8, Q6P7Q4, Q6PAY8, Q75HE6, Q8H0V3

Diamond homologs: A8XX92, P0A0T2, P0A0T3, P0A1Q2, P0A1Q3, P0AC81, P0AC82, P0AC83, P46235, Q09253, Q5I0D1, Q9CPV4, Q9HC38, Q9KT93

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1435 predictions. Top by Δscore:

Variant	Effect	Δscore
17:769867:A:AC	donor_gain	1.0000
17:769868:C:CC	donor_gain	1.0000
17:769868:CAT:C	donor_gain	1.0000
17:769963:A:T	acceptor_gain	1.0000
17:770036:ATACT:A	donor_loss	1.0000
17:770037:TACTT:T	donor_loss	1.0000
17:770038:ACTTA:A	donor_loss	1.0000
17:770039:CT:C	donor_loss	1.0000
17:770040:TT:T	donor_loss	1.0000
17:770041:TACA:T	donor_loss	1.0000
17:770042:A:AC	donor_gain	1.0000
17:770042:A:T	donor_loss	1.0000
17:770043:C:CC	donor_gain	1.0000
17:770043:CA:C	donor_gain	1.0000
17:770043:CAG:C	donor_gain	1.0000
17:770043:CAGG:C	donor_gain	1.0000
17:770043:CAGGG:C	donor_gain	1.0000
17:770061:C:CT	donor_loss	1.0000
17:770155:CAA:C	acceptor_gain	1.0000
17:770155:CAACT:C	acceptor_gain	1.0000
17:770158:C:CC	acceptor_gain	1.0000
17:770159:T:C	acceptor_gain	1.0000
17:770159:T:TC	acceptor_gain	1.0000
17:770508:C:CC	acceptor_gain	1.0000
17:771320:CTCA:C	donor_loss	1.0000
17:771321:TCA:T	donor_loss	1.0000
17:771322:CA:C	donor_loss	1.0000
17:771323:A:AC	donor_gain	1.0000
17:771324:C:CC	donor_gain	1.0000
17:771324:C:G	donor_loss	1.0000

AlphaMissense

1966 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:769917:A:C	F276L	0.990
17:769917:A:T	F276L	0.990
17:769919:A:G	F276L	0.990
17:770443:G:T	A218D	0.988
17:770452:C:T	G215E	0.987
17:776928:A:C	F82L	0.986
17:776928:A:T	F82L	0.986
17:776930:A:G	F82L	0.986
17:776953:C:T	G74E	0.985
17:769938:G:C	C269W	0.984
17:771405:A:G	W170R	0.983
17:771405:A:T	W170R	0.983
17:769933:A:T	V271D	0.982
17:769940:A:G	C269R	0.982
17:770494:A:G	L201P	0.982
17:770500:A:G	L199P	0.982
17:776917:A:G	L86P	0.982
17:770054:A:G	L260P	0.981
17:770449:C:G	R216T	0.981
17:782190:G:C	F22L	0.980
17:782190:G:T	F22L	0.980
17:782192:A:G	F22L	0.980
17:770448:T:A	R216S	0.979
17:770448:T:G	R216S	0.979
17:770452:C:A	G215V	0.978
17:782229:G:C	F9L	0.978
17:782229:G:T	F9L	0.978
17:782231:A:G	F9L	0.978
17:776919:T:A	E85D	0.977
17:776919:T:G	E85D	0.977

dbSNP variants (sampled 300 via entrez): RS1000062636 (17:759579 G>A), RS1000116664 (17:765274 C>A), RS1000192306 (17:786700 C>T), RS1000224066 (17:787468 G>T), RS1000304722 (17:779498 C>T), RS1000387183 (17:782045 T>G), RS1000635563 (17:780861 A>C), RS1000719775 (17:781078 G>T), RS1000855903 (17:786924 C>G), RS1000884730 (17:775019 G>A,C), RS1000933558 (17:787840 C>T), RS1000936512 (17:781164 A>C,T), RS1000969347 (17:786381 C>T), RS1001055193 (17:769458 G>A), RS1001186914 (17:773005 A>T)

Disease associations

OMIM: gene MIM:620650 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001942_3	Prostate cancer	5.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295951 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	2
sodium arsenite	decreases expression, affects expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
beta-lapachone	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
tamibarotene	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Ethanol	decreases expression	1
Amphotericin B	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Cyclophosphamide	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gentamicins	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Thiram	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118732	Binding	Binding affinity to GLOD4 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1SX	Abcam HeLa GLOD4 KO	Cancer cell line	Female
CVCL_SQ05	HAP1 GLOD4 (-) 1	Cancer cell line	Male
CVCL_XP16	HAP1 GLOD4 (-) 2	Cancer cell line	Male
CVCL_XP17	HAP1 GLOD4 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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