OSGIN1

Summary

OSGIN1 (oxidative stress induced growth inhibitor 1, HGNC:30093) is a protein-coding gene on chromosome 16q23.3, encoding Oxidative stress-induced growth inhibitor 1 (Q9UJX0). Monooxygenase catalytic activity.

This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product.

Source: NCBI Gene 29948 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_182981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30093
Approved symbol	OSGIN1
Name	oxidative stress induced growth inhibitor 1
Location	16q23.3
Locus type	gene with protein product
Status	Approved
Aliases	BDGI, OKL38
Ensembl gene	ENSG00000140961
Ensembl biotype	protein_coding
OMIM	607975
Entrez	29948

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000343939, ENST00000361711, ENST00000393306, ENST00000563248, ENST00000563543, ENST00000565123, ENST00000566667, ENST00000567707, ENST00000858442, ENST00000858443, ENST00000858444, ENST00000858445, ENST00000858446, ENST00000858447, ENST00000858448, ENST00000858449

RefSeq mRNA: 1 — MANE Select: NM_182981 NM_182981

CCDS: CCDS10939

Canonical transcript exons

ENST00000393306 — 6 exons

Exon	Start	End
ENSE00000945798	83960569	83960760
ENSE00000945799	83960981	83961072
ENSE00001013991	83959260	83959396
ENSE00001391041	83965062	83966332
ENSE00002595999	83953240	83953370
ENSE00003637052	83957640	83957738

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 96.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3205 / max 399.7117, expressed in 1551 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155274	15.3118	1551
155273	0.0087	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.72	gold quality
liver	UBERON:0002107	89.90	gold quality
adrenal tissue	UBERON:0018303	89.43	gold quality
type B pancreatic cell	CL:0000169	88.75	silver quality
hindlimb stylopod muscle	UBERON:0004252	88.50	gold quality
parotid gland	UBERON:0001831	87.88	gold quality
left adrenal gland	UBERON:0001234	87.62	gold quality
left testis	UBERON:0004533	87.61	gold quality
left adrenal gland cortex	UBERON:0035825	87.18	gold quality
triceps brachii	UBERON:0001509	87.09	silver quality
right testis	UBERON:0004534	86.87	gold quality
olfactory bulb	UBERON:0002264	86.54	gold quality
gastrocnemius	UBERON:0001388	86.46	gold quality
adrenal cortex	UBERON:0001235	86.23	gold quality
adrenal gland	UBERON:0002369	85.87	gold quality
gluteal muscle	UBERON:0002000	85.62	silver quality
right adrenal gland	UBERON:0001233	85.40	gold quality
muscle of leg	UBERON:0001383	85.30	gold quality
tendon of biceps brachii	UBERON:0008188	85.24	silver quality
right adrenal gland cortex	UBERON:0035827	84.59	gold quality
testis	UBERON:0000473	84.50	gold quality
muscle organ	UBERON:0001630	83.83	gold quality
tongue squamous epithelium	UBERON:0006919	83.77	gold quality
buccal mucosa cell	CL:0002336	83.47	silver quality
small intestine Peyer’s patch	UBERON:0003454	83.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.21	silver quality
duodenum	UBERON:0002114	83.10	gold quality
vena cava	UBERON:0004087	83.10	silver quality
body of stomach	UBERON:0001161	82.87	gold quality
body of tongue	UBERON:0011876	82.81	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, TP53

Literature-anchored findings (GeneRIF, showing 12)

• Expression in cultured tumor cells resulted in growth inhibition and cell death. (PMID:14570898)
• The 5’UTRs of OKL38 might play an important role in downregulation of its protein and the absence of OKL38 could lead to the development or progression of hepatocellular carcinoma. (PMID:16924236)
• identify OKL38 as a novel p53 target gene that is regulated by Peptidylarginine deiminase 4 and plays a role in apoptosis (PMID:18499678)
• Data suggest that OKL38 regulates mitochondria morphology and functions during apoptosis together with p53. (PMID:22912861)
• Identify OSGIN1 as a tumor suppressor that is down-regulated or altered in human hepatocellular carcinoma. (PMID:24417816)
• miR-320a has a role in modulating the induction of HO-1, GCLM and OKL38 by oxidized phospholipids in endothelial cells (PMID:24786516)
• The results support the concept that smoking-induced upregulation of OSGIN1 is one link between smoking-induced stress and enhanced-autophagy in the human airway epithelium. (PMID:28548877)
• Bone marrow stromal cell-derived growth inhibitor serves as a stress sensor to induce autophagy. (PMID:31945190)
• A novel biochemical marker -OKL38- with its apoptotic and antioxidant properties for the development of PCOS and its related clinical implications. (PMID:31996062)
• using purified OSGEPL1, we identified multiple acetylation sites, and OSGEPL1 activity was readily affected by acetylation via multiple mechanisms in vitro and in vivo. (PMID:32047918)
• OSGIN1 is a novel TUBB3 regulator that promotes tumor progression and gefitinib resistance in non-small cell lung cancer. (PMID:37646890)
• OSGIN1 regulates PM2.5-induced fibrosis via mediating autophagy in an in vitro model of COPD. (PMID:39260748)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Osgin1	ENSMUSG00000074063
rattus_norvegicus	Osgin1	ENSRNOG00000014948
caenorhabditis_elegans		WBGENE00017934

Paralogs (1): OSGIN2 (ENSG00000164823)

Protein

Protein identifiers

Oxidative stress-induced growth inhibitor 1 — Q9UJX0 (reviewed: Q9UJX0)

Alternative names: Bone marrow stromal cell-derived growth inhibitor, Ovary, kidney and liver protein 38, Pregnancy-induced growth inhibitor OKL38

All UniProt accessions (3): Q9UJX0, H3BTF9, J3KRK7

UniProt curated annotations — full annotation on UniProt →

Function. Monooxygenase catalytic activity. Involved in regulation of cytokinesis; promotes RHOA activity, probably acting locally at the midbody in late cytokinesis. Monooxygenase activity is involved in stabilizing transient structures between daughter cells, termed intercellular bridges, before abscission. Regulates differentiation and proliferation through the regulation of cell death.

Subcellular location. Midbody.

Tissue specificity. Ubiquitous. Highest expression in the ovary, testis, kidney, skeletal muscle and liver.

Cofactor. No monooxygenase catalytic activity in the absence of NADPH.

Induction. By pregnancy.

Miscellaneous. Loss of OSGIN1 protein disturbs the balance between cell growth, differentiation, and cell death in normal tissue, resulting in uncontrolled growth and formation of tumors.

Similarity. Belongs to the OKL38 family.

RefSeq proteins (1): NP_892026* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029731	OSGIN1/2	Family
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily

UniProt features (3 total): chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJX0-F1	88.91	0.68

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): 12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH, GOMF_GROWTH_FACTOR_ACTIVITY, TGACCTY_ERR1_Q2, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOMF_SIGNALING_RECEPTOR_BINDING, ACEVEDO_LIVER_CANCER_UP, GOBP_CELL_GROWTH, GOBP_REGULATION_OF_GROWTH, GOCC_MIDBODY, ER_Q6_02

GO Biological Process (3): cell differentiation (GO:0030154), negative regulation of cell growth (GO:0030308), signal transduction (GO:0007165)

GO Molecular Function (4): monooxygenase activity (GO:0004497), growth factor activity (GO:0008083), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (1): midbody (GO:0030496)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular developmental process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
oxidoreductase activity	1
receptor ligand activity	1
binding	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1179 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSGIN1	NQO1	P15559	586
OSGIN1	TXNRD1	Q16881	573
OSGIN1	SRXN1	Q9BYN0	505
OSGIN1	PADI4	Q9UM07	420
OSGIN1	MANSC4	A6NHS7	384
OSGIN1	TRIM16L	Q309B1	375
OSGIN1	STARD6	P59095	372
OSGIN1	CHAC1	Q9BUX1	370
OSGIN1	STARD9	Q9P2P6	368
OSGIN1	GCLM	P48507	362
OSGIN1	GLTPD2	A6NH11	342
OSGIN1	HMOX1	P09601	331
OSGIN1	LRIT2	A6NDA9	324
OSGIN1	OGFRL1	Q5TC84	315
OSGIN1	NFE2L2	Q16236	311

IntAct

149 interactions, top by confidence:

A	B	Type	Score
OSGIN1	INCA1	psi-mi:“MI:0915”(physical association)	0.720
LNX1	OSGIN1	psi-mi:“MI:0915”(physical association)	0.720
OSGIN1	LNX1	psi-mi:“MI:0915”(physical association)	0.720
INCA1	OSGIN1	psi-mi:“MI:0915”(physical association)	0.720
OSGIN1	MEIS2	psi-mi:“MI:0915”(physical association)	0.670
OSGIN1	TCF4	psi-mi:“MI:0915”(physical association)	0.670
OSGIN1	CAPN3	psi-mi:“MI:0915”(physical association)	0.670
OSGIN1	TCF12	psi-mi:“MI:0915”(physical association)	0.670
OSGIN1	IKZF3	psi-mi:“MI:0915”(physical association)	0.670
MEIS2	OSGIN1	psi-mi:“MI:0915”(physical association)	0.670
CAPN3	OSGIN1	psi-mi:“MI:0915”(physical association)	0.670
TCF12	OSGIN1	psi-mi:“MI:0915”(physical association)	0.670
TCF4	OSGIN1	psi-mi:“MI:0915”(physical association)	0.670
IKZF3	OSGIN1	psi-mi:“MI:0915”(physical association)	0.670
BCAR3	OSGIN1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (62): OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), OSGIN1 (Two-hybrid), CCDC33 (Two-hybrid), LNX1 (Two-hybrid), FAM154A (Two-hybrid), INCA1 (Two-hybrid), OSGIN1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A097ZPG2, A0A0E3D8M4, A0A0F7TXA5, A0A0F7TXA8, A0A0L1JEZ9, A0A0M9ER62, A0A0U5HAQ4, A0A140JWS7, A0A1E1FFN4, A0A1E1FFN7, A0A2I1BSU0, A0A2I1C3T9, A0A2I2F2K8, A0A411PQP8, A1A653, A2QK68, A8NF99, B2KWH9, B8NM63, B8NM73, C4R702, C8VE79, D2E9W9, D4AU57, E9QYP0, F2QY27, F2R038, G2QA95, G5EB76, I1RF61, I1RN13, J4W6X9, M1W850, M2PP75, N4WYI1, P04841, P04842, P0DXV5, P0DXV6, P15245

Diamond homologs: Q8VC10, Q9UJX0, Q9Y236

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1710 predictions. Top by Δscore:

Variant	Effect	Δscore
16:83957735:GTGG:G	donor_gain	1.0000
16:83957736:TGGG:T	donor_loss	1.0000
16:83957737:GG:G	donor_gain	1.0000
16:83957738:GG:G	donor_gain	1.0000
16:83957738:GGTG:G	donor_loss	1.0000
16:83957739:G:GG	donor_gain	1.0000
16:83957739:G:T	donor_loss	1.0000
16:83957740:T:A	donor_loss	1.0000
16:83957741:GAGT:G	donor_loss	1.0000
16:83959254:CCCCA:C	acceptor_loss	1.0000
16:83959255:CCCAG:C	acceptor_loss	1.0000
16:83959256:CCAG:C	acceptor_loss	1.0000
16:83959257:CA:C	acceptor_loss	1.0000
16:83959258:A:AG	acceptor_gain	1.0000
16:83959258:AG:A	acceptor_gain	1.0000
16:83959258:AGGTA:A	acceptor_loss	1.0000
16:83959259:G:GG	acceptor_gain	1.0000
16:83959259:GG:G	acceptor_gain	1.0000
16:83959259:GGT:G	acceptor_gain	1.0000
16:83959259:GGTA:G	acceptor_gain	1.0000
16:83959259:GGTAA:G	acceptor_gain	1.0000
16:83959357:G:GT	donor_gain	1.0000
16:83959393:CCAG:C	donor_loss	1.0000
16:83959396:GG:G	donor_loss	1.0000
16:83959397:G:GA	donor_loss	1.0000
16:83959398:T:G	donor_loss	1.0000
16:83960566:CA:C	acceptor_loss	1.0000
16:83960567:A:AG	acceptor_gain	1.0000
16:83960568:G:GT	acceptor_gain	1.0000
16:83960691:G:GT	donor_gain	1.0000

AlphaMissense

3100 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:83965301:T:A	V243D	0.993
16:83960755:T:A	W131R	0.988
16:83960755:T:C	W131R	0.988
16:83965471:G:C	A300P	0.987
16:83965516:T:C	F315L	0.983
16:83965518:C:A	F315L	0.983
16:83965518:C:G	F315L	0.983
16:83965909:G:A	G446R	0.982
16:83965909:G:C	G446R	0.982
16:83965475:T:A	V301D	0.981
16:83960726:T:A	V121D	0.979
16:83961008:A:C	S142R	0.978
16:83961010:C:A	S142R	0.978
16:83961010:C:G	S142R	0.978
16:83965466:C:A	A298D	0.978
16:83965510:C:G	H313D	0.977
16:83965436:T:A	V288D	0.976
16:83965909:G:T	G446W	0.975
16:83965939:T:C	F456L	0.975
16:83965941:T:A	F456L	0.975
16:83965941:T:G	F456L	0.975
16:83965582:T:C	Y337H	0.973
16:83959296:T:C	L35P	0.970
16:83965439:T:C	L289P	0.970
16:83965900:T:G	Y443D	0.970
16:83960689:T:A	W109R	0.969
16:83960689:T:C	W109R	0.969
16:83965439:T:A	L289H	0.969
16:83965465:G:C	A298P	0.969
16:83965937:G:C	R455T	0.969

dbSNP variants (sampled 300 via entrez): RS1000315414 (16:83957269 G>A,T), RS1000450064 (16:83957888 T>TTTA), RS1000775709 (16:83960315 G>A), RS1000919316 (16:83956384 A>G,T), RS1001003857 (16:83954168 T>C), RS1001042595 (16:83952531 A>G), RS1001081410 (16:83961610 A>G,T), RS1001310500 (16:83956504 T>C), RS1001359485 (16:83957231 A>G), RS1001759139 (16:83953025 G>C), RS1002101525 (16:83963641 G>C), RS1002283445 (16:83960066 T>C), RS1002352915 (16:83957580 C>A,T), RS1002358881 (16:83952112 C>A,G,T), RS1002370683 (16:83956149 G>A)

Disease associations

OMIM: gene MIM:607975 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004097_3	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	3.000000e-06
GCST005024_95	Pursuit maintenance gain	3.000000e-06
GCST006612_49	LDL cholesterol	6.000000e-10
GCST90011898_48	Alanine aminotransferase levels	1.000000e-19
GCST90011900_144	Serum alkaline phosphatase levels	1.000000e-24
GCST90013405_70	Liver enzyme levels (alanine transaminase)	5.000000e-30
GCST90013406_273	Liver enzyme levels (alkaline phosphatase)	1.000000e-36

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007943	response to platinum-based neoadjuvant chemotherapy
EFO:0008433	pursuit maintenance gain measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	8
bisphenol A	increases methylation, increases expression, affects expression, affects cotreatment	4
sodium arsenite	increases expression	4
Cisplatin	affects cotreatment, increases expression, decreases expression	4
Cyclosporine	increases expression	4
lead acetate	increases expression	3
cobaltous chloride	increases expression	3
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	3
enniatins	increases expression, affects cotreatment, decreases expression	3
Air Pollutants	increases abundance, increases expression	3
Particulate Matter	increases abundance, increases expression	3
beauvericin	affects cotreatment, decreases expression, increases expression	2
aflatoxin B2	increases methylation, affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	increases expression	2
Arsenic	increases expression, decreases reaction, increases reaction, increases abundance	2
Copper	affects binding, increases expression	2
Hydrogen Peroxide	increases expression, affects expression	2
Plant Extracts	affects cotreatment, decreases expression, increases expression	2
Silicon Dioxide	increases expression	2
Silver	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	increases expression	2
beta-Naphthoflavone	increases expression	2
tert-Butylhydroperoxide	increases expression, affects expression	2
Vitamin K 3	affects expression, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
chloroacetaldehyde	increases expression	1
hydroxyethyl methacrylate	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0JI	Ubigene HeLa OSGIN1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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