UBN1

Summary

UBN1 (ubinuclein 1, HGNC:12506) is a protein-coding gene on chromosome 16p13.3, encoding Ubinuclein-1 (Q9NPG3). Acts as a novel regulator of senescence.

Cellular senescence is a hallmark of tumor suppression and tissue aging. Senescent cells contain domains of heterochromatin, called senescence-associated heterochromatin foci (SAHF), that repress proliferation-promoting genes. The protein encoded by this gene binds to proliferation-promoting genes and is required for SAHF formation, enhancing methylation of histone H3.

Source: NCBI Gene 29855 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 43 total — 1 likely-pathogenic
• MANE Select transcript: NM_001079514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12506
Approved symbol	UBN1
Name	ubinuclein 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000118900
Ensembl biotype	protein_coding
OMIM	609771
Entrez	29855

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000262376, ENST00000396658, ENST00000585857, ENST00000586152, ENST00000586716, ENST00000587027, ENST00000589191, ENST00000590769, ENST00000592120, ENST00000879302, ENST00000931634

RefSeq mRNA: 2 — MANE Select: NM_001079514 NM_001079514, NM_001288656

CCDS: CCDS10525, CCDS73822

Canonical transcript exons

ENST00000262376 — 18 exons

Exon	Start	End
ENSE00000802202	4876871	4877111
ENSE00000802205	4873031	4873073
ENSE00000802209	4871155	4871301
ENSE00000898366	4874211	4875434
ENSE00000898370	4870844	4870972
ENSE00000898371	4870516	4870634
ENSE00001010738	4857990	4858076
ENSE00001010739	4852879	4853166
ENSE00001010740	4860664	4861102
ENSE00001010741	4859025	4859159
ENSE00001010742	4858568	4858663
ENSE00001145129	4872884	4872934
ENSE00002913606	4847481	4848210
ENSE00003506737	4870212	4870341
ENSE00003534848	4877385	4877474
ENSE00003552538	4859865	4859968
ENSE00003608604	4868833	4868903
ENSE00003892782	4880083	4882401

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.9286 / max 713.9909, expressed in 1817 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152501	21.1322	1817
152500	1.0347	353
152503	0.9648	539
152507	0.2206	83
152506	0.1980	85
152502	0.1784	71
152505	0.1157	27
152504	0.0840	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.45	gold quality
tendon of biceps brachii	UBERON:0008188	96.32	gold quality
secondary oocyte	CL:0000655	95.05	gold quality
sural nerve	UBERON:0015488	94.94	gold quality
pylorus	UBERON:0001166	94.85	gold quality
cardia of stomach	UBERON:0001162	94.47	gold quality
nipple	UBERON:0002030	94.38	gold quality
visceral pleura	UBERON:0002401	94.19	gold quality
blood	UBERON:0000178	94.05	gold quality
oocyte	CL:0000023	93.79	gold quality
parietal pleura	UBERON:0002400	93.66	gold quality
cervix squamous epithelium	UBERON:0006922	93.55	silver quality
sperm	CL:0000019	93.42	gold quality
buccal mucosa cell	CL:0002336	93.40	gold quality
male germ cell	CL:0000015	93.14	gold quality
renal medulla	UBERON:0000362	93.00	gold quality
pleura	UBERON:0000977	92.89	gold quality
esophagus mucosa	UBERON:0002469	91.94	gold quality
pancreatic ductal cell	CL:0002079	91.36	gold quality
testis	UBERON:0000473	90.99	gold quality
right testis	UBERON:0004534	90.98	gold quality
mammary duct	UBERON:0001765	90.80	gold quality
parotid gland	UBERON:0001831	90.78	gold quality
left testis	UBERON:0004533	90.78	gold quality
germinal epithelium of ovary	UBERON:0001304	90.76	gold quality
trabecular bone tissue	UBERON:0002483	90.66	gold quality
epithelium of mammary gland	UBERON:0003244	90.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.08	gold quality
amniotic fluid	UBERON:0000173	89.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.58
E-MTAB-7303	no	430.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

Literature-anchored findings (GeneRIF, showing 10)

• Analyses have revealed that in most cells ubinuclein occurred in the nucleoplasm, but in cells forming tight junctions it is recruited to the plaque structure of the zonula occludens. (PMID:18823282)
• Hpc2-related domain of UBN1, UBN2, and Hpc2p is an evolutionarily conserved HIRA/Hir-binding domain, which directly interacts with the N-terminal WD repeats of HIRA/Hir. (PMID:19029251)
• By a chromatin immunoprecipitation (ChIP) assay, the authors show that Ubn-1 blocks EB1-human herpesvirus 4 DNA interaction. (PMID:21084479)
• Data show that, like HIRA, UBN1, and ASF1a, CABIN1 is involved in heterochromatinization of the genome of senescent human cells. (PMID:21807893)
• a 184-amino acid region (from amino acids 39 to 223) at the N-terminal region of Ubn-1 was responsible for the interaction with the PDZ2 domain of ZO-1 (PMID:22245583)
• NHRD domain of UBN1 as being an essential region for HIRA interaction and chromatin organization by the HUCA complex (PMID:22401310)
• study points to UBN1 as the determinant of H3.3-specific binding and deposition by the HIRA histone chaperone complex. (PMID:26159857)
• analysis of the trimeric HIRA, UBN1 and CABIN1 H3.3 histone chaperone complex (PMID:30082790)
• UBN1 may be capable of binding two H3.3/H4 molecules to facilitate (H3.3/H4)2 tetramer formation in a pathway to nucleosome deposition that may also involve UBN1-mediated DNA binding by the HIRA complex. (PMID:31040182)
• Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells. (PMID:37949972)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubn1	ENSDARG00000063169
mus_musculus	Ubn1	ENSMUSG00000039473
rattus_norvegicus	Ubn1	ENSRNOG00000003019

Paralogs (1): UBN2 (ENSG00000157741)

Protein

Protein identifiers

Ubinuclein-1 — Q9NPG3 (reviewed: Q9NPG3)

Alternative names: HIRA-binding protein, Protein VT4, Ubiquitously expressed nuclear protein

All UniProt accessions (5): Q9NPG3, K7EJT1, K7EQR1, K7ER78, K7ESM4

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a novel regulator of senescence. Involved in the formation of senescence-associated heterochromatin foci (SAHF), which represses expression of proliferation-promoting genes. Binds to proliferation-promoting genes. May be required for replication-independent chromatin assembly.

Subunit / interactions. Component of a complex that includes at least ASF1A, CABIN1, HIRA, histone H3.3 and UBN1. Interacts with HIRA (via WD repeat domain); the interaction is direct. Interacts with ASF1A, CEBPA, TJP1, TJP2 and TJP3. (Microbial infection) Interacts with Epstein-Barr virus BZLF1.

Subcellular location. Nucleus. Nucleoplasm. PML body. Cell junction. Tight junction.

Tissue specificity. Ubiquitous. Also expressed in numerous tumors and cancer cell lines.

Similarity. Belongs to the ubinuclein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPG3-1	1	yes
Q9NPG3-2	2

RefSeq proteins (2): NP_001072982, NP_001275585 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014840	HRD	Domain
IPR026947	UBN_middle_dom	Domain

Pfam: PF08729, PF14075

UniProt features (52 total): compositionally biased region 14, region of interest 11, modified residue 11, mutagenesis site 5, sequence conflict 5, chain 1, coiled-coil region 1, splice variant 1, sequence variant 1, helix 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4ZBJ	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPG3-F1	55.79	0.11

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 (11): 166, 173, 175, 222, 323, 336, 338, 493, 660, 677, 1025

Mutagenesis-validated functional residues (5):

Position	Phenotype
138	strongly diminishes interaction with hira; when associated with e-139 and l-140.
139	strongly diminishes interaction with hira; when associated with e-138 and l-140.
140	strongly diminishes interaction with hira; when associated with e-138 and l-139.
160	strongly diminishes interaction with hira.
162	strongly diminishes interaction with hira.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2559584	Formation of Senescence-Associated Heterochromatin Foci (SAHF)

MSigDB gene sets: 173 (showing top): MODULE_45, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GTGCCTT_MIR506, AGTCTTA_MIR499, MORF_RAF1, BLALOCK_ALZHEIMERS_DISEASE_UP, MARTIN_NFKB_TARGETS_DN, MARTIN_VIRAL_GPCR_SIGNALING_DN, ACATTCC_MIR1_MIR206, AACTTT_UNKNOWN, GOBP_REGULATION_OF_CHROMATIN_ORGANIZATION, TGAGATT_MIR216, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P

GO Biological Process (2): chromatin organization (GO:0006325), nucleosome assembly (GO:0006334)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), bicellular tight junction (GO:0005923), nuclear body (GO:0016604), PML body (GO:0016605), centriolar satellite (GO:0034451), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DNA Damage/Telomere Stress Induced Senescence	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular component organization	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
apical junction complex	1
tight junction	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear body	1
centrosome	1
cell junction	1

Protein interactions and networks

STRING

954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBN1	CABIN1	Q9Y6J0	997
UBN1	ASF1A	Q9Y294	986
UBN1	HIRA	P54198	983
UBN1	ERGIC2	Q96RQ1	846
UBN1	WTAP	Q15007	807
UBN1	SRSF1	Q07955	675
UBN1	DAXX	Q9UER7	669
UBN1	ATRX	P46100	644
UBN1	OGT	O15294	640
UBN1	RAE1	P78406	588
UBN1	PPL	O60437	587
UBN1	ASF1B	Q9NVP2	575
UBN1	NISCH	Q9Y2I1	565
UBN1	THOC2	Q8NI27	548
UBN1	DDX39B	Q13838	547

IntAct

59 interactions, top by confidence:

A	B	Type	Score
ASF1A	HIRA	psi-mi:“MI:0914”(association)	0.900
UBN1	HIRA	psi-mi:“MI:0914”(association)	0.710
HIRA	UBN1	psi-mi:“MI:0914”(association)	0.710
HIRA	UBN1	psi-mi:“MI:0915”(physical association)	0.710
HIRA	UBN1	psi-mi:“MI:0407”(direct interaction)	0.710
ASF1A	HAT1	psi-mi:“MI:0914”(association)	0.640
ASF1B	HAT1	psi-mi:“MI:0914”(association)	0.640
HIRA	CSPG5	psi-mi:“MI:0914”(association)	0.530
ASF1A	MCM4	psi-mi:“MI:0914”(association)	0.530
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
USP7	UBN1	psi-mi:“MI:0407”(direct interaction)	0.440
UBN1	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
UBN1	DHX9	psi-mi:“MI:0915”(physical association)	0.400
UBN1		psi-mi:“MI:0914”(association)	0.350
ORF73	ECI2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
TCF7L2	LOC401309	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (136): UBN1 (Proximity Label-MS), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-Western), UBN1 (Affinity Capture-MS), UBN1 (Affinity Capture-Western), UBN1 (Reconstituted Complex), CABIN1 (Affinity Capture-Western), HIRA (Affinity Capture-Western), OGT (Affinity Capture-Western)

ESM2 similar proteins: A0JLT2, A4QNZ7, A5PK23, B1AZP2, F5HSE3, O60293, O75420, O95402, P61129, P78312, P97839, Q03111, Q07FY3, Q08C81, Q08DM1, Q174D3, Q1LVC2, Q32NP7, Q3T044, Q4G0F8, Q5EAY2, Q5F368, Q5R8Q8, Q5U2R6, Q6DD45, Q6DRL8, Q6PEI3, Q7TN02, Q80Z38, Q8C1B1, Q8C1S0, Q8CFT2, Q8CGI1, Q8IVL1, Q8K4J6, Q90YL3, Q90YY5, Q969V6, Q96A73, Q99MR1

Diamond homologs: D4A666, E1B7L7, P25992, Q4G0F8, Q6ZU65, Q80WC1, Q9NPG3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBN1	“form complex”	“HIRA complex 1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Polyadenylation	6	13.5×	4e-04
mRNA Splicing - Major Pathway	9	12.6×	3e-06
Dengue Virus-Host Interactions	10	11.7×	2e-06
Processing of Capped Intron-Containing Pre-mRNA	5	10.5×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	8	22.5×	8e-07
osteoblast differentiation	5	12.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	0
Likely benign	4
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
190453	NM_001079514.3(UBN1):c.2356T>A (p.Leu786Met)	Likely pathogenic

SpliceAI

3686 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4853136:G:T	donor_gain	1.0000
16:4857971:T:TA	acceptor_gain	1.0000
16:4857976:C:CA	acceptor_gain	1.0000
16:4857988:A:AG	acceptor_gain	1.0000
16:4857989:G:GG	acceptor_gain	1.0000
16:4858073:A:G	donor_gain	1.0000
16:4858073:ATAC:A	donor_gain	1.0000
16:4858074:TAC:T	donor_gain	1.0000
16:4858075:ACGTA:A	donor_loss	1.0000
16:4858076:CGTAA:C	donor_loss	1.0000
16:4858077:G:GG	donor_gain	1.0000
16:4858077:GTA:G	donor_loss	1.0000
16:4858078:T:G	donor_loss	1.0000
16:4858561:A:AG	acceptor_gain	1.0000
16:4858564:TTA:T	acceptor_loss	1.0000
16:4858565:TAGGG:T	acceptor_loss	1.0000
16:4858566:A:AG	acceptor_gain	1.0000
16:4858566:AG:A	acceptor_gain	1.0000
16:4858566:AGG:A	acceptor_gain	1.0000
16:4858566:AGGGT:A	acceptor_gain	1.0000
16:4858567:G:A	acceptor_gain	1.0000
16:4858567:G:GC	acceptor_gain	1.0000
16:4858567:GGG:G	acceptor_gain	1.0000
16:4858567:GGGTG:G	acceptor_gain	1.0000
16:4858660:GGCG:G	donor_gain	1.0000
16:4858661:GCGG:G	donor_gain	1.0000
16:4859023:A:AG	acceptor_gain	1.0000
16:4859024:G:GG	acceptor_gain	1.0000
16:4859861:TCAG:T	acceptor_loss	1.0000
16:4859862:CAG:C	acceptor_loss	1.0000

AlphaMissense

7356 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:4858622:G:C	G131R	1.000
16:4858625:T:C	Y132H	1.000
16:4858637:G:C	D136H	1.000
16:4858638:A:C	D136A	1.000
16:4858638:A:G	D136G	1.000
16:4858638:A:T	D136V	1.000
16:4858643:T:A	F138I	1.000
16:4858643:T:C	F138L	1.000
16:4858644:T:C	F138S	1.000
16:4858644:T:G	F138C	1.000
16:4858645:C:A	F138L	1.000
16:4858645:C:G	F138L	1.000
16:4858647:T:A	I139N	1.000
16:4858647:T:G	I139S	1.000
16:4858649:G:C	D140H	1.000
16:4858650:A:C	D140A	1.000
16:4858650:A:G	D140G	1.000
16:4858650:A:T	D140V	1.000
16:4858651:T:A	D140E	1.000
16:4858651:T:G	D140E	1.000
16:4858654:C:A	N141K	1.000
16:4858654:C:G	N141K	1.000
16:4858655:T:C	S142P	1.000
16:4859028:G:C	D146H	1.000
16:4859029:A:C	D146A	1.000
16:4859029:A:G	D146G	1.000
16:4859029:A:T	D146V	1.000
16:4859035:T:C	L148P	1.000
16:4859038:T:A	V149D	1.000
16:4859040:C:A	P150T	1.000

dbSNP variants (sampled 300 via entrez): RS1000040940 (16:4862545 T>A), RS1000079466 (16:4853701 A>G), RS1000095915 (16:4870784 A>C,T), RS1000114284 (16:4863499 A>G), RS1000149274 (16:4866944 G>A,C), RS1000287561 (16:4862102 T>G), RS1000392248 (16:4862667 T>G), RS1000536199 (16:4853903 C>T), RS1000541861 (16:4854531 A>G,T), RS1000643412 (16:4874142 A>G), RS1000753926 (16:4846575 G>A,C), RS1000753932 (16:4878893 T>G), RS1000756785 (16:4874326 G>A), RS1000802659 (16:4849691 A>G), RS1000894237 (16:4865886 C>T)

Disease associations

OMIM: gene MIM:609771 | disease phenotypes: MIM:236750

GenCC curated gene-disease

Mondo (1): non-immune hydrops fetalis (MONDO:0009369)

Orphanet (1): Non-immune hydrops fetalis (Orphanet:363999)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003542_157	Night sleep phenotypes	1.000000e-06
GCST011011_35	Youthful appearance (self-reported)	3.000000e-08
GCST90002390_79	Mean corpuscular hemoglobin	6.000000e-16
GCST90002392_495	Mean corpuscular volume	3.000000e-16
GCST90002395_185	Mean platelet volume	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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
Air Pollutants	decreases expression, increases abundance, affects expression, affects cotreatment	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
sodium arsenate	increases abundance, increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Dimethyl Sulfoxide	increases expression	1
Selenium	decreases expression, increases expression, affects cotreatment	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis