PIGBOS1

Summary

PIGBOS1 (PIGB opposite strand 1, HGNC:50696) is a protein-coding gene on chromosome 15q21.3, encoding Protein PIGBOS1 (A0A0B4J2F0). Plays a role in regulation of the unfolded protein response triggered by endoplasmic reticulum (ER) stress resulting from the presence of unfolded proteins in the ER lumen.

Involved in regulation of endoplasmic reticulum unfolded protein response. Located in mitochondrial outer membrane.

Source: NCBI Gene 101928527 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001308421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:50696
Approved symbol	PIGBOS1
Name	PIGB opposite strand 1
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000225973
Ensembl biotype	protein_coding
OMIM	618809
Entrez	101928527

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000436697, ENST00000565225, ENST00000567948, ENST00000858450, ENST00000858451, ENST00000919552, ENST00000919553

RefSeq mRNA: 3 — MANE Select: NM_001308421 NM_001308421, NM_001308422, NM_001308423

CCDS: CCDS81884

Canonical transcript exons

ENST00000436697 — 2 exons

Exon	Start	End
ENSE00001734672	55317184	55317867
ENSE00001992047	55318864	55319123

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 90.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.8684 / max 55.4616, expressed in 1518 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150088	12.1395	1805
150087	2.8684	1518

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	90.63	gold quality
leukocyte	CL:0000738	90.30	gold quality
calcaneal tendon	UBERON:0003701	85.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.70	gold quality
granulocyte	CL:0000094	85.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.28	gold quality
placenta	UBERON:0001987	84.02	gold quality
descending thoracic aorta	UBERON:0002345	82.79	gold quality
islet of Langerhans	UBERON:0000006	82.74	gold quality
left lobe of thyroid gland	UBERON:0001120	82.63	gold quality
right lobe of thyroid gland	UBERON:0001119	82.55	gold quality
body of stomach	UBERON:0001161	82.33	gold quality
thyroid gland	UBERON:0002046	82.32	gold quality
bone marrow	UBERON:0002371	82.23	gold quality
left uterine tube	UBERON:0001303	82.21	gold quality
left coronary artery	UBERON:0001626	82.18	gold quality
thoracic aorta	UBERON:0001515	81.94	gold quality
gastrocnemius	UBERON:0001388	81.81	gold quality
ascending aorta	UBERON:0001496	81.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.74	gold quality
spleen	UBERON:0002106	81.71	gold quality
fundus of stomach	UBERON:0001160	81.70	gold quality
vermiform appendix	UBERON:0001154	81.69	gold quality
blood	UBERON:0000178	81.67	gold quality
muscle of leg	UBERON:0001383	81.67	gold quality
bone marrow cell	CL:0002092	81.58	gold quality
left adrenal gland	UBERON:0001234	81.57	gold quality
lymph node	UBERON:0000029	81.55	gold quality
mucosa of transverse colon	UBERON:0004991	81.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.03
E-MTAB-2983	no	176.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ATF4	Repression
DDIT3	Repression

miRNA regulators (miRDB)

25 targeting PIGBOS1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
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-4503	99.85	71.45	1869
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 1)

• PIGBOS regulates the unfolded protein response (UPR). PIGBOS localizes to the mitochondrial outer membrane where it interacts with the ER protein CLCC1 at ER-mitochondria contact sites. Functional studies reveal that the loss of PIGBOS leads to heightened UPR and increased cell death. (PMID:31653868)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pigbos1	ENSMUSG00000098332
rattus_norvegicus	Pigbos1	ENSRNOG00000067122

Protein

Protein identifiers

Protein PIGBOS1 — A0A0B4J2F0 (reviewed: A0A0B4J2F0)

Alternative names: PIGB opposite strand protein 1

All UniProt accessions (2): A0A0B4J2F0, A0A087WXK0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in regulation of the unfolded protein response triggered by endoplasmic reticulum (ER) stress resulting from the presence of unfolded proteins in the ER lumen.

Subunit / interactions. Homooligomer. Interacts (via C-terminus) with endoplasmic reticulum (ER) protein CLCC1; the interaction occurs at the mitochondria-associated ER membrane, a zone of contact between the ER and mitochondrial membranes, but does not appear to play a role in ER-mitochondria tethering and is not affected by ER stress.

Subcellular location. Mitochondrion outer membrane.

RefSeq proteins (3): NP_001295350, NP_001295351, NP_001295352 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR057394	PIGBOS1	Family

Pfam: PF23670

UniProt features (13 total): mutagenesis site 8, topological domain 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A0B4J2F0-F1	85.40	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (8):

Position	Phenotype
46–48	does not affect mitochondrial location or interaction with clcc1.
49–51	does not affect mitochondrial location or interaction with clcc1.
52–54	does not affect mitochondrial location or interaction with clcc1.
30–32	does not affect mitochondrial location but reduces interaction with clcc1.
34–36	does not affect mitochondrial location but reduces interaction with clcc1.
37–39	does not affect mitochondrial location or interaction with clcc1.
40–42	does not affect mitochondrial location or interaction with clcc1.
43–45	does not affect mitochondrial location or interaction with clcc1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_ENDOPLASMIC_RETICULUM_UNFOLDED_PROTEIN_RESPONSE, GOBP_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOCC_ORGANELLE_ENVELOPE, GOBP_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, CBX5_TARGET_GENES, DLX6_TARGET_GENES, E2F2_TARGET_GENES, ELF2_TARGET_GENES, NKX2_2_TARGET_GENES, RFX7_TARGET_GENES

GO Biological Process (2): response to unfolded protein (GO:0006986), regulation of endoplasmic reticulum unfolded protein response (GO:1900101)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to topologically incorrect protein	1
endoplasmic reticulum unfolded protein response	1
regulation of intracellular signal transduction	1
regulation of response to endoplasmic reticulum stress	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGBOS1	HIGD2A	Q9BW72	609
PIGBOS1	TMEM242	Q9NWH2	490
PIGBOS1	PIGB	Q92521	474
PIGBOS1	OXLD1	Q5BKU9	474
PIGBOS1	C22orf39	Q6P5X5	466
PIGBOS1	RMDN3	Q96TC7	463
PIGBOS1	MRPL24	Q96A35	446
PIGBOS1	LYRM9	A8MSI8	443
PIGBOS1	MBLAC2	Q68D91	440
PIGBOS1	TMEM256	Q8N2U0	437
PIGBOS1	PUSL1	Q8N0Z8	434
PIGBOS1	ANTKMT	Q9BQD7	403
PIGBOS1	SMIM26	A0A096LP01	399
PIGBOS1	MIEF1	Q9NQG6	396
PIGBOS1	MTERF4	Q7Z6M4	396

IntAct

14 interactions, top by confidence:

A	B	Type	Score
PIGBOS1	CLCC1	psi-mi:“MI:0915”(physical association)	0.630
PIGBOS1	CLCC1	psi-mi:“MI:2364”(proximity)	0.630
PIGBOS1	CLCC1	psi-mi:“MI:0403”(colocalization)	0.630
PIGBOS1	PIGBOS1	psi-mi:“MI:0915”(physical association)	0.400
PIGBOS1	Pigbos1	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0A0B4J2F0, A0A1D8PLP3, A1XQS1, A5E7J0, A5Z2X5, A7TQM5, A8E7D3, B3DFP2, B7Z0X7, C0HK61, C0HK65, C0HLN0, C5DE77, C6Y4A3, E0CX11, E1BHC3, G2TRJ9, L0R6Q1, O13931, O22912, O74433, O94705, P07255, P0DJ07, P0DJE0, P0DKM0, P0DP99, P19173, P20610, P22289, P48505, P81449, P81450, Q02820, Q42841, Q54QR8, Q6BPV1, Q6CCF6, Q6CMH6, Q6CS34

Diamond homologs: A0A0B4J2F0, C0HLN0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CLCC1	“up-regulates activity”	PIGBOS1	binding
PIGBOS1	“down-regulates quantity by repression”	ATF4	“transcriptional regulation”
PIGBOS1	down-regulates	Apoptosis
PIGBOS1	“down-regulates quantity by repression”	DDIT3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

326 predictions. Top by Δscore:

Variant	Effect	Δscore
15:55319410:GGGG:G	donor_gain	1.0000
15:55319411:GGG:G	donor_gain	1.0000
15:55319411:GGGG:G	donor_gain	1.0000
15:55319412:GG:G	donor_gain	1.0000
15:55319412:GGG:G	donor_gain	1.0000
15:55319412:GGGTG:G	donor_loss	1.0000
15:55319413:GG:G	donor_gain	1.0000
15:55319415:T:A	donor_loss	1.0000
15:55318932:T:TA	donor_gain	0.9900
15:55319409:CGGGG:C	donor_gain	0.9900
15:55319410:GGGGG:G	donor_gain	0.9900
15:55319414:G:GG	donor_gain	0.9900
15:55319416:GAGT:G	donor_loss	0.9900
15:55319417:A:AG	donor_gain	0.9900
15:55319418:G:GG	donor_gain	0.9900
15:55319234:G:GT	donor_gain	0.9800
15:55319235:A:T	donor_gain	0.9600
15:55319417:AGTG:A	donor_loss	0.9600
15:55317865:AATCT:A	acceptor_loss	0.9500
15:55317867:TCTGC:T	acceptor_loss	0.9500
15:55317868:C:CG	acceptor_loss	0.9500
15:55317869:T:A	acceptor_loss	0.9500
15:55317876:A:T	acceptor_gain	0.9300
15:55318932:TCCG:T	donor_gain	0.9300
15:55317872:A:C	acceptor_gain	0.9200
15:55318967:TCGC:T	donor_gain	0.9200
15:55317868:C:CC	acceptor_gain	0.9100
15:55317872:A:AC	acceptor_gain	0.9100
15:55319259:GCCCC:G	donor_gain	0.9000
15:55319340:C:T	donor_gain	0.9000

AlphaMissense

349 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:55317744:C:G	G17R	0.966
15:55317744:C:T	G17R	0.966
15:55317735:C:G	G20R	0.965
15:55317735:C:T	G20R	0.965
15:55317734:C:T	G20E	0.949
15:55317737:G:T	A19D	0.947
15:55317743:C:T	G17E	0.947
15:55317746:A:T	L16H	0.894
15:55317732:C:G	G21R	0.893
15:55317732:C:T	G21R	0.893
15:55317731:C:T	G21E	0.890
15:55317755:G:T	A13D	0.890
15:55317746:A:C	L16R	0.889
15:55317749:A:T	V15D	0.880
15:55317726:A:C	Y23D	0.867
15:55317740:A:T	I18N	0.859
15:55317706:A:C	F29L	0.847
15:55317706:A:T	F29L	0.847
15:55317708:A:G	F29L	0.847
15:55317722:A:T	I24N	0.843
15:55317761:A:C	L11R	0.839
15:55317764:A:G	L10P	0.814
15:55317718:A:C	F25L	0.788
15:55317718:A:T	F25L	0.788
15:55317720:A:G	F25L	0.788
15:55317746:A:G	L16P	0.786
15:55317761:A:T	L11H	0.768
15:55317713:G:T	P27Q	0.758
15:55317743:C:A	G17V	0.758
15:55317707:A:C	F29C	0.755

dbSNP variants (sampled 300 via entrez): RS1000042045 (15:55317020 G>A), RS1003051521 (15:55319155 T>G), RS1003272084 (15:55319067 G>C), RS1003747857 (15:55320735 T>C), RS1003843804 (15:55316745 G>C), RS1005539931 (15:55317853 G>A,T), RS1005763332 (15:55317295 C>T), RS1005870975 (15:55319416 G>A), RS1005944189 (15:55319587 G>A), RS1006151156 (15:55318722 AAAC>A), RS1006228552 (15:55317541 C>A), RS1006511537 (15:55318416 AG>A), RS1007054526 (15:55316899 A>G), RS1007087540 (15:55318343 C>G,T), RS1007222890 (15:55318105 T>TTG)

Disease associations

OMIM: gene MIM:618809 | 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)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12050587	PIGB, PIGBOS1	3	0.50	1	cyclophosphamide;epirubicin;fluorouracil
rs2290344	PIGB, PIGBOS1		0.00	0
rs8024695	PIGB, PIGBOS1		0.00	0

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
Doxorubicin	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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