UTF1

Summary

UTF1 (undifferentiated embryonic cell transcription factor 1, HGNC:12634) is a protein-coding gene on chromosome 10q26.3, encoding Undifferentiated embryonic cell transcription factor 1 (Q5T230). Acts as a transcriptional coactivator of ATF2.

The protein encoded by this gene is a leucine zipper-containing transcriptional coactivator that may link the upstream activator ATF2 with the basal transcription complex. The encoded protein is closely associated with chromatin and is required for the proper differentiation of embryonic carcinoma and embryonic stem cells. Found nearly exclusively in pluripotent cells, this protein can also serve as a transcriptional repressor.

Source: NCBI Gene 8433 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_003577

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12634
Approved symbol	UTF1
Name	undifferentiated embryonic cell transcription factor 1
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171794
Ensembl biotype	protein_coding
OMIM	604130
Entrez	8433

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000304477

RefSeq mRNA: 1 — MANE Select: NM_003577 NM_003577

CCDS: CCDS31318

Canonical transcript exons

ENST00000304477 — 2 exons

Exon	Start	End
ENSE00001152962	133230967	133231558
ENSE00001250336	133230217	133230838

Expression profiles

Bgee: expression breadth broad, 21 present calls, max score 81.41.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5845 / max 942.0273, expressed in 262 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107757	2.8177	119
107763	0.3120	130
107761	0.1285	57
107758	0.1110	42
107760	0.1021	51
107762	0.0835	41
107759	0.0297	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.92	silver quality
pancreatic ductal cell	CL:0002079	69.78	silver quality
Brodmann (1909) area 10	UBERON:0013541	68.92	gold quality
endometrium epithelium	UBERON:0004811	68.61	gold quality
endothelial cell	CL:0000115	67.99	silver quality
right testis	UBERON:0004534	65.57	gold quality
left testis	UBERON:0004533	64.55	gold quality
frontal pole	UBERON:0002795	63.66	gold quality
testis	UBERON:0000473	63.34	gold quality
granulocyte	CL:0000094	63.06	gold quality
paraflocculus	UBERON:0005351	62.62	gold quality
tendon of biceps brachii	UBERON:0008188	62.62	gold quality
middle frontal gyrus	UBERON:0002702	62.21	gold quality
monocyte	CL:0000576	61.26	gold quality
leukocyte	CL:0000738	61.21	gold quality
mononuclear cell	CL:0000842	61.15	gold quality
upper leg skin	UBERON:0004262	55.95	gold quality
lateral globus pallidus	UBERON:0002476	55.18	gold quality
epithelial cell of pancreas	CL:0000083	52.89	gold quality
quadriceps femoris	UBERON:0001377	52.88	gold quality
medial globus pallidus	UBERON:0002477	52.81	gold quality
right uterine tube	UBERON:0001302	52.79	gold quality
thymus	UBERON:0002370	52.74	gold quality
cranial nerve II	UBERON:0000941	52.27	silver quality
globus pallidus	UBERON:0001875	52.26	gold quality
vastus lateralis	UBERON:0001379	51.37	gold quality
bone marrow cell	CL:0002092	50.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.81	gold quality
myocardium	UBERON:0002349	49.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	845.85
E-MTAB-7008	yes	56.68
E-ANND-3	no	0.37

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
CA9
CDKN1B	Unknown
FBXO15
TCF3
UTF1

Upstream regulators (CollecTRI, top): POU5F1, SOX2, UTF1, ZFP42

miRNA regulators (miRDB)

2 targeting UTF1, 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-1234-3P	86.70	58.45	109
HSA-MIR-7107-5P	86.70	59.28	110

Literature-anchored findings (GeneRIF, showing 12)

• The expression pattern indicated that UTF-1 plays a possible role in spermatogonial self-renewal (PMID:18281244)
• enhances reprogramming efficiency of pluripotent stem cells generation induced from human adult fibroblasts (PMID:18983962)
• Human UTF1 is a tightly DNA-associated protein with transcriptional repressor activity. (PMID:19393592)
• Single SNPs did not alter the chromatin association and mobility of hUTF1; however, the double mutant, G73R/L275M, demonstrated a decreased chromatin association, indicating a degree of protein malfunction. (PMID:20218897)
• Strong UTF1 staining can be used for diagnosing embryonal carcinoma and seminoma. UTF1 expression in spermatogonia suggests its possible role in spermatogenesis and renewal of spermatogonia. (PMID:20855642)
• role for UTF1 in differentiation of matrix cells of the shaft as well as in suprabasal keratinocytes. (PMID:21446939)
• These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis. (PMID:22880087)
• Utf1 couples the core pluripotency factors with Myc and PRC2 networks to promote the pluripotency and proliferation of embryonic stem cells. (PMID:23101626)
• UTF1 attenuates cell proliferation and is inactivated in cervical carcinogenesis through epigenetic modification. (PMID:23536577)
• With a sensitivity of 100% and a specificity of 97% in the detection of central nervous system (CNS) germinomas, UTF1 serves as a new reliable alternative in the diagnostic setting of CNS germ cell tumours. (PMID:24614704)
• The Sumo proteome of proliferating and neuronal-differentiating cells reveals Utf1 among key Sumo targets involved in neurogenesis. (PMID:33753728)
• Sox9 downregulation in non-obstructive azoospermia by UTF1 and mediator role of POU5F1. (PMID:38486279)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-261j15.2	ENSDARG00000096411
drosophila_melanogaster	meso18E	FBGN0040089

Paralogs (2): MSANTD2 (ENSG00000120458), MSANTD7 (ENSG00000284024)

Protein

Protein identifiers

Undifferentiated embryonic cell transcription factor 1 — Q5T230 (reviewed: Q5T230)

All UniProt accessions (1): Q5T230

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional coactivator of ATF2.

Subunit / interactions. Binds to the N-terminal region of ATF2. Associates with the TFIID complex through interaction with TBP.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated.

Domain organisation. The leucine-zipper domain is required for coactivation activity. When this domain is deleted, the protein is able to stimulate transcription from a number of gene promoters.

RefSeq proteins (1): NP_003568* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR044822	Myb_DNA-bind_4	Domain

Pfam: PF13837

UniProt features (12 total): region of interest 3, modified residue 3, mutagenesis site 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T230-F1	67.17	0.28

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 (3): 18, 21, 54

Mutagenesis-validated functional residues (2):

Position	Phenotype
296	abolishes coactivation activity; when associated with p-303.
303	abolishes coactivation activity; when associated with p-296.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, CONRAD_STEM_CELL, YAMAZAKI_TCEB3_TARGETS_DN, GOBP_MALE_SEX_DIFFERENTIATION, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, BENPORATH_ES_1, RASHI_RESPONSE_TO_IONIZING_RADIATION_1, GOMF_TRANSCRIPTION_COACTIVATOR_ACTIVITY, MEISSNER_BRAIN_HCP_WITH_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, BILANGES_SERUM_SENSITIVE_GENES, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), male gonad development (GO:0008584), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (2): transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	1
gonad development	1
development of primary male sexual characteristics	1
regulation of transcription by RNA polymerase II	1
transcription coregulator activity	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UTF1	NANOG	Q9H9S0	818
UTF1	DPPA3	Q6W0C5	737
UTF1	SALL4	Q9UJQ4	719
UTF1	POU5F1	P31359	718
UTF1	SOX2	P48431	705
UTF1	LIN28A	Q9H9Z2	683
UTF1	TBP	P20226	678
UTF1	ZFP42	Q96MM3	665
UTF1	ESRRB	O95718	652
UTF1	MYC	P01106	636
UTF1	ZBTB16	Q05516	635
UTF1	KLF4	P78338	634
UTF1	DPPA2	Q7Z7J5	634
UTF1	DPPA4	Q7L190	632
UTF1	GDF3	Q9NR23	630

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TRIP10	UTF1	psi-mi:“MI:0915”(physical association)	0.560
TSKS	RGPD8	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
TRIP10	UTF1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): UTF1 (Affinity Capture-MS), UTF1 (Two-hybrid), UTF1 (Reconstituted Complex), ATF2 (Two-hybrid), UTF1 (Negative Genetic), UTF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0JNN8, A6NF83, A6NHQ4, A6QPM6, A8E4L3, A8MTW9, B2KGE5, C9JVW0, I3L1E1, O43541, O75474, O75638, P0C7X2, P70339, P89439, Q02080, Q05215, Q12950, Q3SYB3, Q5T230, Q5VV16, Q6NZ36, Q6NZY7, Q6P1X6, Q6VB84, Q6VUC0, Q6VUP9, Q6ZSJ8, Q7RTU5, Q7TNS8, Q80WY3, Q86SI9, Q86UU5, Q8K025

Diamond homologs: Q5T230, Q6J1H4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“Av/b1 integrin”	“up-regulates quantity by expression”	UTF1
“A6/b1 integrin”	“up-regulates quantity by expression”	UTF1

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

83 predictions. Top by Δscore:

Variant	Effect	Δscore
10:133230835:CCAGG:C	donor_loss	0.9500
10:133230836:CAGGT:C	donor_loss	0.9500
10:133230837:AGG:A	donor_loss	0.9500
10:133230838:GGTA:G	donor_loss	0.9500
10:133230839:GTAGG:G	donor_loss	0.9500
10:133230840:T:G	donor_loss	0.9500
10:133230711:G:GT	donor_gain	0.9200
10:133230965:A:AG	acceptor_gain	0.9100
10:133230966:G:GG	acceptor_gain	0.9100
10:133230966:GAC:G	acceptor_gain	0.9000
10:133230961:TCCCA:T	acceptor_loss	0.8100
10:133230962:CCCAG:C	acceptor_loss	0.8100
10:133230963:CCAGA:C	acceptor_loss	0.8100
10:133230964:CAG:C	acceptor_loss	0.8100
10:133230965:AGA:A	acceptor_loss	0.8100
10:133230965:AGAC:A	acceptor_gain	0.7000
10:133230966:GACG:G	acceptor_gain	0.7000
10:133230966:GACGC:G	acceptor_gain	0.7000
10:133230958:C:CA	acceptor_gain	0.6700
10:133230966:GA:G	acceptor_gain	0.6600
10:133230839:G:GG	donor_gain	0.6300
10:133230968:C:CA	acceptor_gain	0.5100
10:133231049:TGCG:T	acceptor_gain	0.4900
10:133231050:GCGG:G	acceptor_gain	0.4900
10:133231254:C:CT	acceptor_gain	0.4900
10:133231255:T:TT	acceptor_gain	0.4900
10:133231030:GCCC:G	acceptor_gain	0.4600
10:133231253:G:GT	acceptor_gain	0.4600
10:133230986:C:A	acceptor_gain	0.4400
10:133230956:C:CA	acceptor_gain	0.4300

AlphaMissense

2131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:133230475:T:A	W63R	0.999
10:133230475:T:C	W63R	0.999
10:133230477:G:C	W63C	0.999
10:133230477:G:T	W63C	0.999
10:133230488:A:T	E67V	0.999
10:133230613:C:A	R109S	0.999
10:133230628:T:C	C114R	0.999
10:133230630:C:G	C114W	0.999
10:133230637:C:A	R117S	0.999
10:133230646:T:C	F120L	0.999
10:133230648:C:A	F120L	0.999
10:133230648:C:G	F120L	0.999
10:133230654:A:C	K122N	0.999
10:133230654:A:T	K122N	0.999
10:133230571:T:C	Y95H	0.998
10:133230627:G:C	Q113H	0.998
10:133230627:G:T	Q113H	0.998
10:133230629:G:A	C114Y	0.998
10:133230640:T:G	Y118D	0.998
10:133230650:T:C	L121P	0.998
10:133230653:A:T	K122I	0.998
10:133230694:T:C	F136L	0.998
10:133230696:C:A	F136L	0.998
10:133230696:C:G	F136L	0.998
10:133231356:T:C	F314L	0.998
10:133231358:C:A	F314L	0.998
10:133231358:C:G	F314L	0.998
10:133230487:G:A	E67K	0.997
10:133230571:T:G	Y95D	0.997
10:133230643:A:G	K119E	0.997

dbSNP variants (sampled 300 via entrez): RS1000832452 (10:133229421 G>A,C), RS1002005357 (10:133229056 C>G), RS1002458680 (10:133230371 C>T), RS1002622890 (10:133230678 C>A,T), RS1004016861 (10:133231949 A>G,T), RS1004494448 (10:133231822 C>G,T), RS1004882590 (10:133230159 A>C,G), RS1005449953 (10:133229794 C>A,T), RS1005752092 (10:133229969 T>G), RS1006453103 (10:133228691 A>T), RS1007413606 (10:133231780 TCA>T), RS1008006321 (10:133231017 A>G), RS1008392810 (10:133231217 C>G,T), RS1008976192 (10:133230160 T>C,G), RS1009007118 (10:133229988 C>T)

Disease associations

OMIM: gene MIM:604130 | 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)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
terbufos	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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