POU3F2

protein-coding

POU class 3 homeobox 2, the group of POU class homeoboxes and pseudogenes

Gene summary

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. [provided by RefSeq, Mar 2012]

Previous symbols:

OTF7

MANE transcript

NM_005604.4

Inheritance

ClinVar variants

P:1U:53B:11

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr6:98,834,574-98,839,458

External References & Databases

Ensembl (ENSG00000184486)

Transcript & Mutation Effects

hg38 • Region Span ~4.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POU3F2 variants in ClinVar

4 Conditions Cataloged

Inborn genetic diseasesTotal: 49

not providedTotal: 16

POU3F2-related disorderTotal: 6

POU3F2-associated disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005604.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				9 clinvar		9
missense		1 clinvar	49 clinvar	2 clinvar		52
nonsense						0
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)						0
Total	0	1	53	11	0	65

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005604.4	RefSeq	NP_005595.2	1	MANE Select
ENST00000328345.8	Ensembl	ENSP00000329170.5	1	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pou3f2b	Danio rerio	Structure: endothelial cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

pou3f2b

Danio rerio

Structure: endothelial cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MECP2 and Associated Rett Syndrome
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways

Biological Process

regulation of transcription by RNA polymerase II
nervous system development
positive regulation of cell population proliferation
epidermis development
negative regulation of gene expression

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity
transcription coactivator activity

Cellular Component

nucleus
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328345
Coding exons: 1
Length: 4081
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.72	108	222	0.486	0.0000102	2841
Missense (PolyPhen)		23	89.007	0.25841		1184
Synonymous	-1.11	117	103	1.14	0.00000502	907
Loss of Function	3.01	1	12.5	0.0800	5.50e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor that plays a key role in neuronal differentiation (By similarity). 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P31360, ECO:0000250|UniProtKB:P56222}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium