POU3F2

Summary

POU3F2 (POU class 3 homeobox 2, HGNC:9215) is a protein-coding gene on chromosome 6q16.1, encoding POU domain, class 3, transcription factor 2 (P20265). Transcription factor that plays a key role in neuronal differentiation.

This gene encodes a member of the POU-III class of neural transcription factors. The encoded protein is involved in neuronal differentiation and enhances the activation of corticotropin-releasing hormone regulated genes. Overexpression of this protein is associated with an increase in the proliferation of melanoma cells.

Source: NCBI Gene 5454 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 30
• Clinical variants (ClinVar): 56 total — 1 likely-pathogenic
• Druggable target: yes
• Transcription factor: yes — 32 downstream targets (CollecTRI)
• MANE Select transcript: NM_005604

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9215
Approved symbol	POU3F2
Name	POU class 3 homeobox 2
Location	6q16.1
Locus type	gene with protein product
Status	Approved
Aliases	POUF3, BRN2, OCT7
Ensembl gene	ENSG00000184486
Ensembl biotype	protein_coding
OMIM	600494
Entrez	5454

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000328345

RefSeq mRNA: 1 — MANE Select: NM_005604 NM_005604

CCDS: CCDS5040

Canonical transcript exons

ENST00000328345 — 1 exons

Exon	Start	End
ENSE00001329549	98834574	98839458

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 98.64.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8758 / max 211.4608, expressed in 318 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68970	0.8522	217
68972	0.7512	211
68974	0.4487	159
68973	0.3119	129
68976	0.2290	123
68975	0.1763	99
68971	0.1065	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.64	gold quality
ventricular zone	UBERON:0003053	97.53	gold quality
buccal mucosa cell	CL:0002336	96.38	gold quality
cortical plate	UBERON:0005343	92.85	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.34	gold quality
medial globus pallidus	UBERON:0002477	88.28	gold quality
embryo	UBERON:0000922	88.09	gold quality
globus pallidus	UBERON:0001875	86.20	gold quality
ventral tegmental area	UBERON:0002691	85.00	gold quality
substantia nigra pars compacta	UBERON:0001965	84.98	gold quality
inferior vagus X ganglion	UBERON:0005363	83.31	gold quality
substantia nigra	UBERON:0002038	80.25	gold quality
primary visual cortex	UBERON:0002436	80.25	gold quality
midbrain	UBERON:0001891	80.24	gold quality
superior vestibular nucleus	UBERON:0007227	80.17	gold quality
medulla oblongata	UBERON:0001896	79.92	gold quality
parietal lobe	UBERON:0001872	79.78	gold quality
postcentral gyrus	UBERON:0002581	79.53	gold quality
occipital lobe	UBERON:0002021	79.45	gold quality
caudate nucleus	UBERON:0001873	79.43	gold quality
entorhinal cortex	UBERON:0002728	78.17	gold quality
amygdala	UBERON:0001876	78.10	gold quality
spinal cord	UBERON:0002240	78.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.01	gold quality
subthalamic nucleus	UBERON:0001906	77.98	gold quality
putamen	UBERON:0001874	77.91	gold quality
temporal lobe	UBERON:0001871	77.82	gold quality
corpus callosum	UBERON:0002336	77.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.65	gold quality
nucleus accumbens	UBERON:0001882	77.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	45.47
E-ANND-3	no	2.12

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

32 targets.

Target	Regulation
AVP	Unknown
BRAF
CD74
CDH13	Unknown
CRH
DDC	Unknown
DLL1	Unknown
EGFR
EGR2	Activation
FABP7	Unknown
FLG
FOXP2	Unknown
GNRH1	Activation
GPX6	Repression
HLA-E
KITLG	Unknown
MAPK1
MITF	Unknown
NAIP
NES	Unknown
NKX2-1	Unknown
OXT
PAX3	Unknown
PDE5A	Repression
POU3F2
RB1
SGPL1
TDO2	Activation
TPH2
TPM1

JASPAR motifs

Motif	Name	Family
MA0787.1	POU3F2	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:9852081

Upstream regulators (CollecTRI, top): PAX3, POU3F2, SOX9, USF1

miRNA regulators (miRDB)

184 targeting POU3F2, 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-7110-3P	100.00	73.18	2486
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6845-3P	99.94	66.88	1439

Literature-anchored findings (GeneRIF, showing 33)

• The results suggest that the high levels of Brn-2 expression observed in melanomas link BRAF signaling to increased proliferation. (PMID:15024080)
• Rb induces a proliferative arrest and regulates Brn-2 expression in retinoblastoma cells (PMID:17163992)
• Brn-2 regulates invasiveness and directly represses Mitf expression. (PMID:18829533)
• SOX9 and SOX10 but not BRN2 seem to be required for nestin expression in human melanoma. (PMID:18923447)
• Expression and purification of full-length BRN2, a transcription factor involved in melanoma growth, are reported. (PMID:18996486)
• POU3F2 may regulate the properties of melanoma cells via autocrine KIT ligand signalling. (PMID:20337985)
• links BRN2 as an activator and MITF as a repressor of the NOTCH pathway in melanoma cells. Loss of the BRN2-MITF axis in antisense-ablated cell lines decreased the melanoma sphere-forming capability and cell adhesion (PMID:21358674)
• a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression. (PMID:21435193)
• PI3K has a crucial role in regulating Brn-2 and Pax3 expression and neoplasm invasiveness, and it is a key determinant of melanoma subpopulation diversity. (PMID:22988297)
• The present study investigated transcriptional regulation of CDH13 in melanoma. Found an inverse correlation between BRN2 and T-cadherin protein and transcript expression in melanoma. (PMID:23069940)
• TTF1 expression in small-cell lung cancer is a cell lineage-specific phenomenon that involves the developing neural cell-specific homeoprotein BRN2. (PMID:23358112)
• BRN2 is a higher level regulator than ASCL1 and ND1 and BRN2 might be involved in aggressiveness of small cell lung cancer. (PMID:23530560)
• We show that POU3F2 lies downstreamof SIM1 and controls oxytocin expression in the hypothalamic neuroendocrine preoptic area. We show that this finding is consistent with the expression patterns of POU3F2 and related genes in the human brain. (PMID:26833329)
• These findings not only shed light on the molecular mechanism of the anticancer properties of capsaicin, but also the transcription regulation of tNOX expression that may potentially explain how POU3F2 is associated with tumorigenesis. (PMID:27271588)
• Re4sults show that BRN2 is: directly transcriptionally repressed by AR, required for the expression of terminal neuroendocrine markers and aggressive growth of castration-resistant prostate cancer (CRPC), and is highly expressed in human neuroendocrine prostate cancer and metastatic CRPC with low circulating PSA. (PMID:27784708)
• Data indicate that NFIB protein increases EZH2 protein expression downstream of BRN2 protein, which further decreases MITF protein levels. (PMID:28119061)
• These results suggest that the proliferative population within melanoma tumors express MITF, and both MITF and BRN2 are important for metastatic growth in vivo. This finding highlights the importance of BRN2 and MITF expression in development of melanoma metastasis. (PMID:28883623)
• NTF3 is a novel target gene of POU3F2 and that the POU3F2/NTF3 pathway plays a role in the process of neuronal differentiation. (PMID:29549646)
• CDKN2A suppresses the initiation of melanoma invasion through inhibition of BRN2. (PMID:29990501)
• POU3F2 may be a key regulator of gene expression in this disease-associated gene coexpression module. (PMID:30545964)
• BRN2 also suppresses an apoptosis-associated gene expression program to protect against UVB-, chemotherapy- and vemurafenib-induced apoptosis. Remarkably, BRN2 expression also correlates with a high single-nucleotide variation prevalence in human melanomas (PMID:30804224)
• BRN4 Is a Novel Driver of Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer and Is Selectively Released in Extracellular Vesicles with BRN2. (PMID:31371344)
• Study investigated super-enhancer profiles in lung squamous cell carcinoma (LUSC) and identified a novel subtype in which SOX2 and a neural transcription factor BRN2 have key roles in determining its distinctive differentiation state. BRN2 serves as an interacting partner for SOX2 in this novel subtype, instead of p63 in the classical subtype of LUSC. (PMID:31551362)
• Unexpected High Levels of BRN2/POU3F2 Expression in Human Dermal Melanocytic Nevi. (PMID:31881210)
• Transcription factor POU3F2 regulates TRIM8 expression contributing to cellular functions implicated in schizophrenia. (PMID:32929213)
• Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder. (PMID:33539344)
• BRN2 is a non-canonical melanoma tumor-suppressor. (PMID:34140478)
• Reciprocal Regulation of BRN2 and NOTCH1/2 Signaling Synergistically Drives Melanoma Cell Migration and Invasion. (PMID:34958806)
• CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to Facilitate SOX9 Transcription. (PMID:35398178)
• Integrin alpha3 Mediates Stemness and Invasion of Glioblastoma by Regulating POU3F2. (PMID:36843258)
• Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene’s candidacy in 6q16.1 deletions. (PMID:37207645)
• CREB1 Facilitates GABAergic Neural Differentiation of Human Mesenchymal Stem Cells through BRN2 for Pain Alleviation and Locomotion Recovery after Spinal Cord Injury. (PMID:38201271)
• RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1. (PMID:38386071)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pou3f2b	ENSDARG00000076262
mus_musculus	Pou3f2	ENSMUSG00000095139
rattus_norvegicus	Pou3f2	ENSRNOG00000063836
drosophila_melanogaster	acj6	FBGN0000028
caenorhabditis_elegans		WBGENE00006818

Paralogs (17): POU2F2 (ENSG00000028277), POU1F1 (ENSG00000064835), POU4F3 (ENSG00000091010), POU6F2 (ENSG00000106536), POU2F3 (ENSG00000137709), POU2F1 (ENSG00000143190), POU4F2 (ENSG00000151615), POU4F1 (ENSG00000152192), HDX (ENSG00000165259), POU6F1 (ENSG00000184271), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), POU3F3 (ENSG00000198914), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

POU domain, class 3, transcription factor 2 — P20265 (reviewed: P20265)

Alternative names: Brain-specific homeobox/POU domain protein 2, Nervous system-specific octamer-binding transcription factor N-Oct-3, Octamer-binding protein 7, Octamer-binding transcription factor 7

All UniProt accessions (1): P20265

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that plays a key role in neuronal differentiation. Binds preferentially to the recognition sequence which consists of two distinct half-sites, (‘GCAT’) and (‘TAAT’), separated by a non-conserved spacer region of 0, 2, or 3 nucleotides. Acts as a transcriptional activator when binding cooperatively with SOX4, SOX11, or SOX12 to gene promoters. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Acts downstream of ASCL1, accessing chromatin that has been opened by ASCL1, and promotes transcription of neuronal genes.

Subunit / interactions. Interacts with PQBP1. Interaction with ISL1.

Subcellular location. Nucleus.

Tissue specificity. Expressed specifically in the neuroectodermal cell lineage.

Similarity. Belongs to the POU transcription factor family. Class-3 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P20265-1	N-OCT 3	yes
P20265-2	N-OCT 5A
P20265-3	N-OCT 5B

RefSeq proteins (1): NP_005595* (*=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
IPR016362	TF_POU_3	Family
IPR017970	Homeobox_CS	Conserved_site
IPR050255	POU_domain_TF	Family

Pfam: PF00046, PF00157

UniProt features (26 total): helix 7, compositionally biased region 6, sequence conflict 3, region of interest 3, splice variant 2, chain 1, domain 1, modified residue 1, DNA-binding region 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7XRC	X-RAY DIFFRACTION	1.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20265-F1	62.74	0.25

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 (1): 341

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-9824594	Regulation of MITF-M-dependent genes involved in apoptosis
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity

MSigDB gene sets: 268 (showing top): BENPORATH_ES_WITH_H3K27ME3, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOBP_GROWTH, GOBP_GLIAL_CELL_DEVELOPMENT, GTTAAAG_MIR302B, GOBP_PITUITARY_GLAND_DEVELOPMENT, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, HNF1_Q6, FOXO1_01, GOBP_CELL_PROLIFERATION_IN_FOREBRAIN, GOBP_FOREBRAIN_DEVELOPMENT, SHEPARD_BMYB_MORPHOLINO_DN

GO Biological Process (25): regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), epidermis development (GO:0008544), negative regulation of gene expression (GO:0010629), cerebral cortex radially oriented cell migration (GO:0021799), forebrain ventricular zone progenitor cell division (GO:0021869), forebrain astrocyte development (GO:0021897), central nervous system neuron differentiation (GO:0021953), hypothalamus cell differentiation (GO:0021979), neurohypophysis development (GO:0021985), myelination in peripheral nervous system (GO:0022011), neuron differentiation (GO:0030182), positive regulation of multicellular organism growth (GO:0040018), regulation of cell differentiation (GO:0045595), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate commitment (GO:0048663), neuron fate specification (GO:0048665), neuron development (GO:0048666), regulation of axonogenesis (GO:0050770), neuroendocrine cell differentiation (GO:0061101), regulation of DNA-templated transcription (GO:0006355), brain development (GO:0007420), Schwann cell development (GO:0014044), cell differentiation (GO:0030154)

GO Molecular Function (9): 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 activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nervous system development	1
MITF-M-dependent gene expression	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron differentiation	3
cell differentiation	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
tissue development	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cerebral cortex cell migration	1
cell proliferation in forebrain	1
cell division	1
astrocyte development	1
forebrain astrocyte differentiation	1
central nervous system development	1
hypothalamus development	1
pituitary gland development	1
gland development	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
myelination	1
generation of neurons	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
regulation of developmental process	1
regulation of cellular process	1
positive regulation of DNA-templated transcription	1
cell fate commitment	1
cell fate specification	1
neuron fate commitment	1
cell development	1
axonogenesis	1

Protein interactions and networks

STRING

1546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU3F2	MYT1L	Q9UL68	969
POU3F2	ASCL1	P50553	968
POU3F2	SOX2	P48431	876
POU3F2	SALL2	Q9Y467	827
POU3F2	OTP	Q5XKR4	774
POU3F2	PQBP1	O60828	742
POU3F2	TBR1	Q16650	716
POU3F2	DLL1	O00548	713
POU3F2	NEUROG2	Q9H2A3	712
POU3F2	SIM1	P81133	708
POU3F2	FOXJ2	Q9P0K8	703
POU3F2	NEUROD1	Q13562	676
POU3F2	PAX6	P26367	670
POU3F2	SOX1	O00570	661
POU3F2	BCL11B	Q9C0K0	661

IntAct

19 interactions, top by confidence:

A	B	Type	Score
POU3F2	EP300	psi-mi:“MI:0915”(physical association)	0.600
POU3F2	EP300	psi-mi:“MI:0407”(direct interaction)	0.600
EP300	POU3F2	psi-mi:“MI:0407”(direct interaction)	0.600
POU3F2	POU3F2	psi-mi:“MI:0915”(physical association)	0.530
TBP	POU3F2	psi-mi:“MI:0915”(physical association)	0.530
SOX10	POU3F2	psi-mi:“MI:0915”(physical association)	0.530
PAX3	POU3F2	psi-mi:“MI:0915”(physical association)	0.530
TBP	POU3F2	psi-mi:“MI:0407”(direct interaction)	0.530
PAX3	POU3F2	psi-mi:“MI:0407”(direct interaction)	0.530
SOX10	POU3F2	psi-mi:“MI:0407”(direct interaction)	0.530
POU3F2	SOX10	psi-mi:“MI:0407”(direct interaction)	0.530
POU3F2	POU3F2	psi-mi:“MI:0407”(direct interaction)	0.530
POU3F2	GTF2B	psi-mi:“MI:0407”(direct interaction)	0.440
	POU3F2	psi-mi:“MI:0915”(physical association)	0.370
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
GRHL1	POLRMT	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): POU3F2 (Affinity Capture-MS), POU3F2 (Affinity Capture-Western), YAP1 (Affinity Capture-Western), POU3F2 (Affinity Capture-Western), POU3F2 (Co-localization), NFYA (Reconstituted Complex), NFYB (Reconstituted Complex), NFYC (Reconstituted Complex), POU3F2 (Affinity Capture-RNA), POU3F2 (Affinity Capture-MS), PQBP1 (Two-hybrid), PQBP1 (Affinity Capture-Western), POU3F2 (Affinity Capture-MS), POU3F2 (Affinity Capture-MS), POU3F2 (Affinity Capture-MS)

ESM2 similar proteins: A2WY46, A6BLW4, B8A9B2, G0SB31, G4MRQ6, G4N3L5, M2TF54, O54772, O65001, O70132, P17208, P20264, P20265, P20266, P20267, P21952, P25209, P31360, P31361, P53784, P56222, Q01851, Q02516, Q03052, Q0JGS5, Q13164, Q60764, Q60EQ4, Q63262, Q655V5, Q69J40, Q69TW5, Q6EU10, Q75IZ7, Q8L4B2, Q8LCG7, Q8LH59, Q8QZW2, Q92925, Q960X8

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

4 interactions.

A	Effect	B	Mechanism
POU3F2	“up-regulates activity”	POU3F2	binding
POU3F2	“up-regulates quantity by expression”	GNRH1	“transcriptional regulation”
POU3F4	“up-regulates activity”	POU3F2	binding
POU3F2	“up-regulates quantity by expression”	MITF	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	46
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
976719	NM_005604.4(POU3F2):c.812A>T (p.Glu271Val)	Likely pathogenic

SpliceAI

61 predictions. Top by Δscore:

Variant	Effect	Δscore
6:98836059:G:GT	donor_gain	0.8900
6:98835955:TCGAG:T	donor_loss	0.8300
6:98835956:CGAG:C	donor_loss	0.8300
6:98835957:GAGGT:G	donor_loss	0.8300
6:98835958:AGG:A	donor_loss	0.8300
6:98835959:GG:G	donor_loss	0.8300
6:98835960:G:A	donor_loss	0.8300
6:98835961:T:TC	donor_loss	0.8300
6:98835962:GA:G	donor_loss	0.8300
6:98838174:A:AG	acceptor_gain	0.8200
6:98836064:G:GA	donor_gain	0.7600
6:98835964:G:C	donor_loss	0.7500
6:98835963:AGCGT:A	donor_loss	0.7400
6:98836063:T:TA	donor_gain	0.7400
6:98835960:G:GG	donor_gain	0.6900
6:98838176:T:TA	acceptor_gain	0.6900
6:98838165:A:AG	acceptor_gain	0.6600
6:98835957:GAG:G	donor_gain	0.6300
6:98836069:G:GT	donor_gain	0.6300
6:98836070:A:T	donor_gain	0.5900
6:98838166:T:G	acceptor_gain	0.5900
6:98836061:GGTG:G	donor_gain	0.5800
6:98836062:GTGG:G	donor_gain	0.5800
6:98836063:T:A	donor_gain	0.5600
6:98836066:TGA:T	donor_gain	0.5600
6:98836067:GAG:G	donor_gain	0.5600
6:98836068:AGA:A	donor_gain	0.5600
6:98836143:G:GT	donor_gain	0.5300
6:98838174:AAT:A	acceptor_gain	0.5200
6:98836060:AGGT:A	donor_gain	0.5100

AlphaMissense

2896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:98835682:T:A	L270Q	1.000
6:98835682:T:C	L270P	1.000
6:98835682:T:G	L270R	1.000
6:98835686:G:C	E271D	1.000
6:98835686:G:T	E271D	1.000
6:98835690:T:A	F273I	1.000
6:98835690:T:C	F273L	1.000
6:98835690:T:G	F273V	1.000
6:98835691:T:C	F273S	1.000
6:98835691:T:G	F273C	1.000
6:98835692:C:A	F273L	1.000
6:98835692:C:G	F273L	1.000
6:98835693:G:A	A274T	1.000
6:98835693:G:C	A274P	1.000
6:98835694:C:A	A274D	1.000
6:98835694:C:T	A274V	1.000
6:98835698:G:C	K275N	1.000
6:98835698:G:T	K275N	1.000
6:98835702:T:A	F277I	1.000
6:98835702:T:C	F277L	1.000
6:98835702:T:G	F277V	1.000
6:98835703:T:C	F277S	1.000
6:98835703:T:G	F277C	1.000
6:98835704:C:A	F277L	1.000
6:98835704:C:G	F277L	1.000
6:98835705:A:C	K278Q	1.000
6:98835705:A:G	K278E	1.000
6:98835706:A:C	K278T	1.000
6:98835706:A:T	K278M	1.000
6:98835707:G:C	K278N	1.000

dbSNP variants (sampled 300 via entrez): RS1000124237 (6:98839532 A>G), RS1000206538 (6:98834546 T>A,C,G), RS1000217603 (6:98834762 G>A,C), RS1000481538 (6:98835671 C>A,T), RS1000551991 (6:98833909 A>G), RS1000813348 (6:98834114 C>A,G), RS1001159830 (6:98834516 C>A,G,T), RS1001785191 (6:98834436 G>A), RS1002237953 (6:98837529 C>G), RS1002457318 (6:98838017 A>C,G,T), RS1002614491 (6:98837738 A>C), RS1002716342 (6:98837230 G>T), RS1003310693 (6:98838723 G>A,C), RS1003466826 (6:98832851 G>A,C), RS1003651143 (6:98839015 C>G)

Disease associations

OMIM: gene MIM:600494 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000271_3	Brain imaging in schizophrenia (dorsolateral prefrontal cortex interaction)	9.000000e-06
GCST001762_449	Obesity-related traits	9.000000e-06
GCST001890_17	QT interval (drug interaction)	6.000000e-06
GCST002385_5	Bipolar disorder	1.000000e-08
GCST002598_7	Educational attainment	2.000000e-09
GCST003724_1	Bipolar disorder	3.000000e-08
GCST003992_39	Photic sneeze reflex	1.000000e-17
GCST004364_2	Intelligence	9.000000e-09
GCST004364_20	Intelligence	4.000000e-11
GCST006922_14	Regular attendance at a religious group	2.000000e-08
GCST006956_12	Erectile dysfunction	2.000000e-06
GCST007323_47	Risk-taking tendency (4-domain principal component model)	4.000000e-08
GCST007323_78	Risk-taking tendency (4-domain principal component model)	2.000000e-10
GCST007325_157	General risk tolerance (MTAG)	1.000000e-11
GCST007325_251	General risk tolerance (MTAG)	2.000000e-09
GCST007326_41	Number of sexual partners	9.000000e-10
GCST007326_50	Number of sexual partners	2.000000e-09
GCST007327_192	Smoking status (ever vs never smokers)	1.000000e-11
GCST007565_53	Morning person	5.000000e-15
GCST007576_351	Chronotype	5.000000e-15
GCST007603_38	Smoking initiation	2.000000e-08
GCST008810_75	Smoking initiation (ever regular vs never regular)	3.000000e-10
GCST009391_1249	Metabolite levels	3.000000e-06
GCST010242_130	HDL cholesterol levels	1.000000e-12
GCST010989_108	Body size at age 10	6.000000e-09
GCST011102_9	Bipolar disorder	4.000000e-09
GCST011126_10	Caffeine consumption from coffee or tea	4.000000e-09
GCST011140_5	Glucagon levels in response to oral glucose tolerance test (decremental area under the curve for 0-30 minutes)	9.000000e-06
GCST011703_76	Smoking initiation	1.000000e-11
GCST012465_18	Bipolar disorder	1.000000e-15

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0005108	arm span
EFO:0004682	QT interval
EFO:0007916	response to tricyclic antidepressant
EFO:0004784	self reported educational attainment
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004337	intelligence
EFO:0009592	social interaction measurement
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0005670	smoking initiation
EFO:0010423	triacylglycerol 54:5 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement
EFO:0008463	glucagon measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4189 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs195862	POU2F2, POU3F2		0.00	0
rs3823036	POU2F2, POU3F2		0.00	0

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Plant Extracts	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
butyraldehyde	increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	increases response to substance	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects binding, decreases expression	1
Flavonoids	increases expression	1
Lead	affects expression	1
Rotenone	decreases expression	1
Silver	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1
Polyphenols	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL832955	Functional	Antagonistic activity against BRN2/DNA interaction by electrophoretic mobility shift assay	Privileged scaffolds for blocking protein-protein interactions: 1,4-disubstituted naphthalene antagonists of transcription factor complex HOX-PBX/DNA. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5L9	SEES3-1V human POU3F2, clone1	Embryonic stem cell	Male
CVCL_A5M0	SEES3-1V human POU3F2, clone2	Embryonic stem cell	Male
CVCL_A5M1	SEES3-1V human POU3F2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice