POU6F1

Summary

POU6F1 (POU class 6 homeobox 1, HGNC:9224) is a protein-coding gene on chromosome 12q13.13, encoding POU domain, class 6, transcription factor 1 (Q14863). Transcription factor that binds preferentially to a variant of the octamer motif (5’-ATGATAAT-3’).

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in actin cytoskeleton and nuclear body.

Source: NCBI Gene 5463 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_001330422

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9224
Approved symbol	POU6F1
Name	POU class 6 homeobox 1
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	BRN5, MPOU, TCFB1
Ensembl gene	ENSG00000184271
Ensembl biotype	protein_coding
OMIM	618043
Entrez	5463

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding_CDS_not_defined, 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000333640, ENST00000546685, ENST00000547854, ENST00000547855, ENST00000548692, ENST00000549309, ENST00000550824, ENST00000552305, ENST00000636068, ENST00000636119, ENST00000636728

RefSeq mRNA: 1 — MANE Select: NM_001330422 NM_001330422

CCDS: CCDS81691

Canonical transcript exons

ENST00000333640 — 11 exons

Exon	Start	End
ENSE00001298815	51191596	51191764
ENSE00001318707	51192330	51192471
ENSE00002390322	51197770	51198023
ENSE00003565061	51195970	51196173
ENSE00003792215	51186936	51190592
ENSE00003793129	51196799	51196927
ENSE00003793717	51198550	51198775
ENSE00003793809	51204173	51204368
ENSE00003798529	51199747	51199868
ENSE00003799445	51206789	51206883
ENSE00003800780	51217642	51218062

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 93.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.3385 / max 71.7681, expressed in 990 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130939	0.9783	471
130938	0.4719	248
130940	0.2891	120
130937	0.2708	122
130935	0.2531	103
130936	0.0752	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	93.70	gold quality
cerebellar hemisphere	UBERON:0002245	93.68	gold quality
cerebellar cortex	UBERON:0002129	93.55	gold quality
right frontal lobe	UBERON:0002810	92.29	gold quality
cerebellum	UBERON:0002037	92.23	gold quality
sural nerve	UBERON:0015488	91.68	gold quality
left ovary	UBERON:0002119	91.64	gold quality
right ovary	UBERON:0002118	91.55	gold quality
endocervix	UBERON:0000458	91.03	gold quality
cortical plate	UBERON:0005343	90.97	gold quality
prefrontal cortex	UBERON:0000451	90.92	gold quality
mucosa of stomach	UBERON:0001199	90.90	gold quality
primary visual cortex	UBERON:0002436	90.28	gold quality
body of uterus	UBERON:0009853	89.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.24	gold quality
cingulate cortex	UBERON:0003027	89.14	gold quality
neocortex	UBERON:0001950	89.08	gold quality
frontal cortex	UBERON:0001870	89.04	gold quality
ganglionic eminence	UBERON:0004023	88.94	gold quality
anterior cingulate cortex	UBERON:0009835	88.94	gold quality
popliteal artery	UBERON:0002250	88.69	gold quality
endothelial cell	CL:0000115	88.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.67	gold quality
tibial artery	UBERON:0007610	88.66	gold quality
caudate nucleus	UBERON:0001873	88.47	gold quality
putamen	UBERON:0001874	88.39	gold quality
occipital lobe	UBERON:0002021	88.38	gold quality
nucleus accumbens	UBERON:0001882	88.37	gold quality
aorta	UBERON:0000947	88.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	22.24
E-ANND-3	no	3.76

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CRH
HTR1A

JASPAR motifs

Motif	Name	Family
MA0628.1	POU6F1	POU domain factors
MA0628.2	POU6F1	POU domain factors
MA1549.1	POU6F1	POU domain factors
MA1549.2	POU6F1	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:9852081, PMID:26265007

Upstream regulators (CollecTRI, top): DEAF1

Literature-anchored findings (GeneRIF, showing 6)

• Crystallization and preliminary X-ray analysis (PMID:18323601)
• The crystal structure of human Brn-5 transcription factor in complex with corticotropin-releasing hormone gene promoter reveals an unexpected recognition mode of the protein to its cognate DNA (PMID:19450691)
• is the transcription factor that might be involved in cell proliferation of clear cell adenocarcinoma of the ovary. (PMID:19874398)
• POU6F1 siRNA dose-dependently suppressed the proliferation of clear cell adenocarcinoma cell lines. (PMID:20134265)
• results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthen the importance of AurkA in skeletal myogenesis (PMID:31665313)
• POU6F1 promotes ferroptosis by increasing lncRNA-CASC2 transcription to regulate SOCS2/SLC7A11 signaling in gastric cancer. (PMID:38267746)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pou6f1	ENSDARG00000011570
mus_musculus	Pou6f1	ENSMUSG00000009739
rattus_norvegicus	Pou6f1	ENSRNOG00000070769
drosophila_melanogaster	acj6	FBGN0000028
drosophila_melanogaster	vvl	FBGN0086680
caenorhabditis_elegans		WBGENE00000441
caenorhabditis_elegans		WBGENE00006818

Paralogs (17): POU2F2 (ENSG00000028277), POU1F1 (ENSG00000064835), POU4F3 (ENSG00000091010), POU6F2 (ENSG00000106536), POU2F3 (ENSG00000137709), POU2F1 (ENSG00000143190), POU4F2 (ENSG00000151615), POU4F1 (ENSG00000152192), HDX (ENSG00000165259), POU3F2 (ENSG00000184486), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), POU3F3 (ENSG00000198914), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

POU domain, class 6, transcription factor 1 — Q14863 (reviewed: Q14863)

Alternative names: Brain-specific homeobox/POU domain protein 5, mPOU homeobox protein

All UniProt accessions (5): A0A1B0GU61, A0A1B0GVK9, A0A1C7CYV8, A0A1C7CYY7, Q14863

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds preferentially to a variant of the octamer motif (5’-ATGATAAT-3’).

Subcellular location. Nucleus.

Tissue specificity. In the embryo, expressed exclusively in the developing brain, whereas in the adult its expression is restricted to brain, heart, skeletal muscle and lung. In the brain, the highest expression levels are found in specific cell layers of the cortex, the olfactory bulb, the hippocampus and the cerebellum.

Similarity. Belongs to the POU transcription factor family. Class-6 subfamily.

RefSeq proteins (1): NP_001317351* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000327	POU_dom	Domain
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR013847	POU	Domain
IPR050255	POU_domain_TF	Family

Pfam: PF00046, PF00157

UniProt features (16 total): helix 8, region of interest 2, chain 1, domain 1, DNA-binding region 1, sequence conflict 1, turn 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3D1N	X-RAY DIFFRACTION	2.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14863-F1	52.80	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 211 (showing top): AGGAAGC_MIR5163P, MORF_FLT1, MORF_MSH3, GOLDRATH_IMMUNE_MEMORY, MORF_BRCA1, MORF_ESR1, MORF_RAD51L3, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GROSS_HYPOXIA_VIA_HIF1A_DN, MORF_PRKCA, GOBP_HEAD_DEVELOPMENT, MORF_ETV3, MULLIGHAN_NPM1_SIGNATURE_3_DN, CONRAD_STEM_CELL, MORF_ATF2

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), brain development (GO:0007420), heart development (GO:0007507), muscle organ development (GO:0007517), regulation of DNA-templated transcription (GO:0006355), central nervous system development (GO:0007417)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), actin cytoskeleton (GO:0015629), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
central nervous system development	1
head development	1
circulatory system development	1
muscle structure development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nervous system development	1
system development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
cytoskeleton	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU6F1	NRG2	O14511	476
POU6F1	MEOX1	P50221	474
POU6F1	GADL1	Q6ZQY3	460
POU6F1	ARHGEF15	O94989	455
POU6F1	CSAD	Q9Y600	450
POU6F1	POU4F2	Q12837	449
POU6F1	SCARF1	Q14162	427
POU6F1	MEF2D	Q14814	427
POU6F1	STAT3	P40763	413
POU6F1	FOXJ2	Q9P0K8	381
POU6F1	EP300	Q09472	379
POU6F1	TMEM161B	Q8NDZ6	365
POU6F1	ARHGAP36	Q6ZRI8	362
POU6F1	POU3F2	P20265	360
POU6F1	HOXB5	P09067	335

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ACOT7	POU6F1	psi-mi:“MI:0915”(physical association)	0.560
NFYC	POU6F1	psi-mi:“MI:0915”(physical association)	0.560
ERBB2	POU6F1	psi-mi:“MI:0915”(physical association)	0.370
IFNA8	POU6F1	psi-mi:“MI:0915”(physical association)	0.370
ACOT7	POU6F1	psi-mi:“MI:0915”(physical association)	0.000
NFYC	POU6F1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): POU6F1 (Two-hybrid), POU6F1 (Two-hybrid), POU6F1 (Two-hybrid)

ESM2 similar proteins: A0JME2, A5D7F6, F8VPZ9, O88873, O89090, P08047, P31367, P52591, P54253, P58929, P70178, P78364, Q01714, Q02086, Q07916, Q08E26, Q13227, Q14863, Q2VPU4, Q3U182, Q5E9U0, Q64028, Q66JY2, Q6AI39, Q6T264, Q7Z3K3, Q8BLM0, Q8BZH4, Q8CHH5, Q8CHP6, Q8IXK0, Q8IZL2, Q8K3Z9, Q8K4J6, Q8N196, Q8N1G0, Q8NDX5, Q8QHL5, Q8VHG2, Q91VX2

Diamond homologs: A0A1L8FFY5, A1L0Z1, A7Y7W2, B3DM23, B3DM25, B7ZQA9, D3ZTL1, G3V7L5, O97552, P09086, P10036, P10037, P13528, P14859, P15143, P16143, P16241, P17208, P20263, P20264, P20265, P20266, P20267, P20268, P20912, P20913, P20914, P21952, P24350, P25425, P28069, P31360, P31361, P31362, P31363, P31364, P31365, P31367, P31368, P31369

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AURKA	“down-regulates activity”	POU6F1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2056 predictions. Top by Δscore:

Variant	Effect	Δscore
12:51190591:ACC:A	acceptor_loss	1.0000
12:51190592:CCTG:C	acceptor_loss	1.0000
12:51190611:C:T	acceptor_gain	1.0000
12:51191760:TGGCT:T	acceptor_gain	1.0000
12:51191763:CT:C	acceptor_gain	1.0000
12:51191765:C:CC	acceptor_gain	1.0000
12:51191771:C:CT	acceptor_gain	1.0000
12:51191771:C:T	acceptor_gain	1.0000
12:51191772:A:T	acceptor_gain	1.0000
12:51192328:A:AC	donor_gain	1.0000
12:51192329:C:CA	donor_gain	1.0000
12:51192329:CTGGA:C	donor_gain	1.0000
12:51192330:TGGA:T	donor_gain	1.0000
12:51192470:ACC:A	acceptor_loss	1.0000
12:51192472:C:CG	acceptor_loss	1.0000
12:51192473:T:G	acceptor_loss	1.0000
12:51195973:A:AC	donor_gain	1.0000
12:51195974:C:CC	donor_gain	1.0000
12:51195974:CT:C	donor_gain	1.0000
12:51195980:G:C	donor_gain	1.0000
12:51198684:ATA:A	acceptor_gain	1.0000
12:51199869:C:CC	acceptor_gain	1.0000
12:51199872:C:CT	acceptor_gain	1.0000
12:51199874:C:CT	acceptor_gain	1.0000
12:51199875:A:T	acceptor_gain	1.0000
12:51199879:CA:C	acceptor_gain	1.0000
12:51199880:A:AC	acceptor_gain	1.0000
12:51199880:A:C	acceptor_gain	1.0000
12:51199880:A:T	acceptor_gain	1.0000
12:51199881:T:C	acceptor_gain	1.0000

AlphaMissense

3885 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000053695 (12:51197716 T>C), RS1000090226 (12:51193709 G>C), RS1000306046 (12:51201444 A>C), RS1000384606 (12:51188761 C>T), RS1000425479 (12:51216796 T>A), RS1000449490 (12:51193505 G>A,T), RS1000482558 (12:51200859 T>G), RS1000503717 (12:51196604 G>A), RS1000512413 (12:51188974 G>A), RS1000543787 (12:51188756 G>A), RS1000559331 (12:51207926 C>T), RS1000563895 (12:51196327 C>T), RS1000574020 (12:51187987 G>A), RS1000610010 (12:51194861 T>A), RS1000962269 (12:51212147 C>G,T)

Disease associations

OMIM: gene MIM:618043 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003898_19	Cisplatin-induced ototoxicity	9.000000e-06
GCST010988_493	Adult body size	8.000000e-09
GCST90002390_59	Mean corpuscular hemoglobin	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006951	ototoxicity
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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
Lead	affects expression, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Tamoxifen	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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