POU4F2

Summary

POU4F2 (POU class 4 homeobox 2, HGNC:9219) is a protein-coding gene on chromosome 4q31.22, encoding POU domain, class 4, transcription factor 2 (Q12837). Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells.

The protein encoded by this gene is a member of the POU-domain transcription factor family and may be involved in maintaining visual system neurons in the retina. The level of the encoded protein is also elevated in a majority of breast cancers, resulting in accelerated tumor growth.

Source: NCBI Gene 5458 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 80 total
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_004575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9219
Approved symbol	POU4F2
Name	POU class 4 homeobox 2
Location	4q31.22
Locus type	gene with protein product
Status	Approved
Aliases	Brn-3b
Ensembl gene	ENSG00000151615
Ensembl biotype	protein_coding
OMIM	113725
Entrez	5458

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000281321

RefSeq mRNA: 1 — MANE Select: NM_004575 NM_004575

CCDS: CCDS34074

Canonical transcript exons

ENST00000281321 — 2 exons

Exon	Start	End
ENSE00001000654	146638893	146639428
ENSE00001000655	146639867	146642474

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 74.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0776 / max 53.2253, expressed in 19 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49926	0.0776	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	74.13	gold quality
pons	UBERON:0000988	72.43	gold quality
pancreatic ductal cell	CL:0002079	61.20	silver quality
decidua	UBERON:0002450	56.55	gold quality
ileal mucosa	UBERON:0000331	56.19	gold quality
upper leg skin	UBERON:0004262	53.38	silver quality
skin of hip	UBERON:0001554	53.37	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
oocyte	CL:0000023	52.24	silver quality
deltoid	UBERON:0001476	51.27	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
quadriceps femoris	UBERON:0001377	50.26	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
trigeminal ganglion	UBERON:0001675	49.87	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
vastus lateralis	UBERON:0001379	49.11	gold quality
oviduct epithelium	UBERON:0004804	48.97	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
sural nerve	UBERON:0015488	48.84	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	576.14
E-ANND-3	no	1.47

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
ACE	Activation
BAX	Activation
BRCA1	Repression
CCND1	Activation
CDH1
CDK4	Activation
DDC
EOMES	Unknown
EPO
ESR1
GH1
GSK3B	Repression
HSP90AA1	Activation
HSPB1	Activation
HTT
INA
JUP
MSTN	Unknown
NCOR1
NOS1
NOS2
NR4A2	Repression
PAX6
PDLIM7
PMAIP1	Unknown
POU4F1	Repression
POU4F3
PRL
RIT2	Activation
SAP30

JASPAR motifs

Motif	Name	Family
MA0683.1	POU4F2	POU domain factors
MA0683.2	POU4F2	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:18077589

Upstream regulators (CollecTRI, top): ATOH7, ISL1, MSX2, NCOR1, POU4F1, SOX2, WT1

miRNA regulators (miRDB)

126 targeting POU4F2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 12)

• Levels of CDK4 mRNA and protein correlate with levels of Brn-3b in breast cancer cell lines manipulated to express different levels of Brn-3b and in human breast cancer biopsies; Brn-3b can activate the CDK4 promoter (PMID:14726699)
• Brn-3b transcription factor contributes to proliferation of neuroblastoma cells in vivo and in vitro but may also influence progression and/or invasion during tumorigenesis. (PMID:14970234)
• Brn-3b can, directly and indirectly (via interaction with the ER), activate HSP-27 expression, and this may represent one mechanism by which Brn-3b mediates its effects in breast cancer cells. (PMID:15833836)
• Brn-3b expression has been shown to be a prerequisite for developmental survival of most retinal ganglion cells. (PMID:15968082)
• first time that a Brn-3b POU family transcription factor has been shown to regulate a member of the catenin family, which provides insight into the molecular mechanisms by which Brn-3b expression may favour breast cancer progression and tumor invasion (PMID:16152597)
• Two different microRNAs that potentially regulate the stability of Brn-3b have been identified in neuroblastoma cells. (PMID:17490655)
• May act to alter growth properties of breast cancer and neuroblastoma cells by enhancing cyclin D1 expression in these tumor cells. (PMID:17637757)
• Brn3b specifies the RGC fate from multipotential precursors not only by promoting RGC differentiation but also by suppressing non-RGC differentiation programs as a safeguard mechanism. (PMID:18367606)
• Methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens are promising diagnostic biomarkers for bladder cancer recurrence surveillance (PMID:23056278)
• The genes BCL6, NFE2, POU4F2 and ELF4 are primary 1,25(OH)2D3 targets in THP-1 cells (PMID:25482012)
• DNA methylation in a combination of POU4F2/PCDH17 has yielded the highest sensitivity and specificity of 90.00% and 93.96% in all the 312 individuals, showing the capability of detecting bladder cancer effectively among pathologically varied sample groups. (PMID:26700620)
• No association between POU4F1, POU4F2, ISL1 polymorphisms and normal-tension glaucoma. (PMID:32597291)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pou4f2	ENSDARG00000069737
mus_musculus	Pou4f2	ENSMUSG00000031688
rattus_norvegicus	Pou4f2	ENSRNOG00000012167
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), POU4F1 (ENSG00000152192), HDX (ENSG00000165259), POU6F1 (ENSG00000184271), POU3F2 (ENSG00000184486), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), POU3F3 (ENSG00000198914), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

POU domain, class 4, transcription factor 2 — Q12837 (reviewed: Q12837)

Alternative names: Brain-specific homeobox/POU domain protein 3B

All UniProt accessions (1): Q12837

UniProt curated annotations — full annotation on UniProt →

Function. Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells. Functions either as activator or repressor modulating the rate of target gene transcription through RNA polymerase II enzyme in a promoter-dependent manner. Binds to the consensus octamer motif 5’-AT[A/T]A[T/A]T[A/T]A-3’ of promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Binds to an octamer site to form a ternary complex with ISL1; cooperates positively with ISL1 and ISL2 to potentiate transcriptional activation of RGC target genes being involved in RGC fate commitment in the developing retina and RGC axon formation and pathfinding. Inhibits DLX1 and DLX2 transcriptional activities preventing DLX1- and DLX2-mediated ability to promote amacrine cell fate specification. In cooperation with TP53 potentiates transcriptional activation of BAX promoter activity increasing neuronal cell apoptosis. Negatively regulates BAX promoter activity in the absence of TP53. Acts as a transcriptional coactivator via its interaction with the transcription factor ESR1 by enhancing its effect on estrogen response element (ERE)-containing promoter. Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to an octamer motif. Involved in TNFSF11-mediated terminal osteoclast differentiation.

Subunit / interactions. Interacts with POU4F1; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities. Interacts (C-terminus) with ESR1 (via DNA-binding domain); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner. Interacts (via C-terminus) with TP53 (via N-terminus). Interacts with DLX1 (via homeobox DNA-binding domain); this interaction suppresses DLX1-mediated transcriptional activity in postnatal retina enhancing retinal ganglion cell (RGC) differentiation. Interacts with DLX2 (via homeobox DNA-binding domain); this interaction enhances RGC differentiation. Interacts (via C-terminus) with ISL1 (via C-terminus). Interacts with ISL2. Interacts with LHX2.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Tissue specificity. Expressed in the brain. Expressed in the ganglion cell layer of the retina.

Domain organisation. The N-terminal transcriptional activation region is sufficient to induce transcriptional activity. The POU-specific domain and POU homeodomain regions are necessary for DNA-binding activity and transcriptional repression. The polyhistidine motif acts as a targeting signal to nuclear speckles.

Similarity. Belongs to the POU transcription factor family. Class-4 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12837-1	1, Brn-3b long, Brn-3b-l	yes
Q12837-2	2, Brn-3b short, Brn-3b-s

RefSeq proteins (1): NP_004566* (*=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
IPR017970	Homeobox_CS	Conserved_site
IPR050255	POU_domain_TF	Family

Pfam: PF00046, PF00157

UniProt features (19 total): compositionally biased region 4, region of interest 4, sequence conflict 3, short sequence motif 2, chain 1, domain 1, splice variant 1, sequence variant 1, mutagenesis site 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12837-F1	63.29	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.

Mutagenesis-validated functional residues (1):

Position	Phenotype
171–185	absent from nuclear speckle; no change in transcriptional activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6804759	Regulation of TP53 Activity through Association with Co-factors

MSigDB gene sets: 302 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, TGCGCANK_UNKNOWN, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, TTTGTAG_MIR520D

GO Biological Process (34): negative regulation of transcription by RNA polymerase II (GO:0000122), MAPK cascade (GO:0000165), regulation of transcription by RNA polymerase II (GO:0006357), axon guidance (GO:0007411), heart development (GO:0007507), sensory perception of sound (GO:0007605), neuron differentiation (GO:0030182), estrogen receptor signaling pathway (GO:0030520), retinal ganglion cell axon guidance (GO:0031290), cellular response to insulin stimulus (GO:0032869), positive regulation of programmed cell death (GO:0043068), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), negative regulation of cell differentiation (GO:0045596), positive regulation of cell differentiation (GO:0045597), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of axon extension (GO:0045773), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of D-glucose import across plasma membrane (GO:0046326), axon extension (GO:0048675), neuromuscular process controlling balance (GO:0050885), obsolete regulation of DNA-binding transcription factor activity (GO:0051090), retina development in camera-type eye (GO:0060041), cellular response to cytokine stimulus (GO:0071345), cellular response to estradiol stimulus (GO:0071392), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), regulation of retinal ganglion cell axon guidance (GO:0090259), negative regulation of amacrine cell differentiation (GO:1902870), negative regulation of adipose tissue development (GO:1904178), dorsal root ganglion development (GO:1990791), positive regulation of transcription regulatory region DNA binding (GO:2000679), regulation of DNA-templated transcription (GO:0006355), apoptotic process (GO:0006915), axonogenesis (GO:0007409), cell differentiation (GO:0030154)

GO Molecular Function (12): 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 activator activity, RNA polymerase II-specific (GO:0001228), p53 binding (GO:0002039), promoter-specific chromatin binding (GO:1990841), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (7): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of TP53 Activity	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
cell differentiation	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
axonogenesis	2
positive regulation of cellular process	2
regulation of cell differentiation	2
chromatin	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
transcription cis-regulatory region binding	2
binding	2
negative regulation of DNA-templated transcription	1
intracellular signaling cassette	1
neuron projection guidance	1
animal organ development	1
circulatory system development	1
sensory perception of mechanical stimulus	1
generation of neurons	1
nuclear receptor-mediated steroid hormone signaling pathway	1
axon guidance	1
response to insulin	1
cellular response to peptide hormone stimulus	1
programmed cell death	1
regulation of programmed cell death	1
negative regulation of cellular process	1
negative regulation of developmental process	1
positive regulation of developmental process	1
positive regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
positive regulation of DNA-templated transcription	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1

Protein interactions and networks

STRING

1146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU4F2	ISL1	P20663	888
POU4F2	ATOH7	Q8N100	837
POU4F2	VSX2	P58304	769
POU4F2	OPN4	Q9UHM6	709
POU4F2	RIT2	Q99578	702
POU4F2	CRX	O43186	645
POU4F2	PAX6	P26367	644
POU4F2	PCDH17	O14917	634
POU4F2	RBPMS	Q93062	621
POU4F2	RCVRN	P35243	603
POU4F2	WTAP	Q15007	596
POU4F2	SNCG	O76070	590
POU4F2	SIX3	O95343	589
POU4F2	FOXN4	Q96NZ1	588
POU4F2	OTX2	P32243	572

IntAct

250 interactions, top by confidence:

A	B	Type	Score
POU4F2	INCA1	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.560
KRT83	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	PLSCR2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LHX2	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
TGFB1	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP5-11	psi-mi:“MI:0915”(physical association)	0.560
DLX3	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	VWC2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-4	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
GRN	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
ALPP	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	POU4F2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	LGALS13	psi-mi:“MI:0915”(physical association)	0.560
CYP21A2	POU4F2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (81): POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid), POU4F2 (Two-hybrid)

ESM2 similar proteins: A2WWU7, A2XZR3, A2ZH47, B1B534, B4NEU8, B8AX53, B8BGV5, G3V7L5, O54743, P10035, P20266, P20268, P22809, P31316, P55316, P56224, P56260, Q07961, Q0J6N4, Q10ED2, Q12837, Q12946, Q12947, Q1A1A4, Q24648, Q25AM2, Q2QXL0, Q33DK1, Q4V5A3, Q5NBM8, Q5VM82, Q5W7C3, Q61080, Q63934, Q67U94, Q688U3, Q6F2E4, Q6S3I3, Q70UV1, Q7XM13

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

2 interactions.

A	Effect	B	Mechanism
POU4F2	“up-regulates activity”	ESR1	binding
ATOH7	“up-regulates quantity by expression”	POU4F2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
Keratinization	34	37.1×	3e-46
Formation of the cornified envelope	7	12.1×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	6	124.8×	2e-09
keratinization	6	31.2×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

54 predictions. Top by Δscore:

Variant	Effect	Δscore
4:146639425:ACCGG:A	donor_loss	0.9900
4:146639427:CGG:C	donor_loss	0.9900
4:146639428:GGT:G	donor_loss	0.9900
4:146639429:G:GG	donor_gain	0.9900
4:146639859:A:AG	acceptor_gain	0.9900
4:146639861:TTGCA:T	acceptor_loss	0.9900
4:146639863:GCAG:G	acceptor_loss	0.9900
4:146639865:A:AG	acceptor_gain	0.9900
4:146639865:AG:A	acceptor_loss	0.9900
4:146639866:G:GG	acceptor_gain	0.9900
4:146639866:GA:G	acceptor_gain	0.9900
4:146639866:GAGC:G	acceptor_gain	0.9900
4:146639866:GAGCA:G	acceptor_gain	0.9900
4:146639426:CCG:C	donor_gain	0.9800
4:146639430:T:A	donor_loss	0.9800
4:146639860:A:G	acceptor_gain	0.9800
4:146639431:GCGTA:G	donor_loss	0.9700
4:146639859:AATT:A	acceptor_gain	0.9700
4:146639864:CAG:C	acceptor_gain	0.9700
4:146639865:AGA:A	acceptor_gain	0.9700
4:146639866:GAG:G	acceptor_gain	0.9700
4:146639424:CACCG:C	donor_gain	0.9600
4:146639425:ACCG:A	donor_gain	0.9600
4:146639427:CG:C	donor_gain	0.9500
4:146639428:GG:G	donor_gain	0.9500
4:146639432:CGTA:C	donor_loss	0.9400
4:146639860:ATTGC:A	acceptor_loss	0.8500
4:146639858:C:G	acceptor_gain	0.8400
4:146641704:T:A	acceptor_gain	0.8300
4:146639857:A:AG	acceptor_gain	0.7800

AlphaMissense

2707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:146640351:T:A	L258Q	1.000
4:146640351:T:C	L258P	1.000
4:146640355:G:C	E259D	1.000
4:146640355:G:T	E259D	1.000
4:146640359:T:A	F261I	1.000
4:146640359:T:C	F261L	1.000
4:146640360:T:C	F261S	1.000
4:146640360:T:G	F261C	1.000
4:146640361:C:A	F261L	1.000
4:146640361:C:G	F261L	1.000
4:146640362:G:C	A262P	1.000
4:146640363:C:A	A262D	1.000
4:146640369:G:C	R264P	1.000
4:146640371:T:C	F265L	1.000
4:146640372:T:C	F265S	1.000
4:146640372:T:G	F265C	1.000
4:146640373:C:A	F265L	1.000
4:146640373:C:G	F265L	1.000
4:146640374:A:C	K266Q	1.000
4:146640374:A:G	K266E	1.000
4:146640375:A:C	K266T	1.000
4:146640375:A:T	K266M	1.000
4:146640376:G:C	K266N	1.000
4:146640376:G:T	K266N	1.000
4:146640378:A:C	Q267P	1.000
4:146640381:G:C	R268P	1.000
4:146640383:C:A	R269S	1.000
4:146640383:C:G	R269G	1.000
4:146640383:C:T	R269C	1.000
4:146640384:G:A	R269H	1.000

dbSNP variants (sampled 300 via entrez): RS1000148561 (4:146637218 G>A), RS1000249553 (4:146641278 T>C), RS1000567213 (4:146637645 G>A), RS1000821601 (4:146639666 C>T), RS1000985954 (4:146642673 G>A,T), RS1001368781 (4:146637175 C>T), RS1002069121 (4:146637189 C>T), RS1002323212 (4:146642588 G>A), RS1002377148 (4:146642304 G>A,T), RS1002525077 (4:146637368 C>G,T), RS1003048194 (4:146639638 G>A), RS1003329789 (4:146641207 T>A,C), RS1003382013 (4:146640888 G>A), RS1003780226 (4:146642161 CA>C), RS1004130856 (4:146637015 A>G)

Disease associations

OMIM: gene MIM:113725 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009391_881	Metabolite levels	1.000000e-06
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010439	triacylglycerol 58:12 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	4
Benzo(a)pyrene	affects expression, affects methylation, increases methylation	2
TAK-243	increases sumoylation	1
daidzein	decreases expression, affects cotreatment	1
potassium perchlorate	decreases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
butylbenzyl phthalate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
glycitein	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
entinostat	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	decreases expression	1
Antimycin A	decreases expression	1
Diazinon	increases methylation	1
Fonofos	increases methylation	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Parathion	increases methylation	1
Rotenone	decreases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3EB	Abcam HEK293T POU4F2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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