POU4F2

POU class 4 homeobox 2, the group of POU class homeoboxes and pseudogenes

Basic information

Region (hg38): 4:146638893-146642474

Previous symbols: [ "BRN3B" ]

Links

ENSG00000151615 ∙ NCBI:5458 ∙ OMIM:113725 ∙ HGNC:9219 ∙ Uniprot:Q12837 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POU4F2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POU4F2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			41	1	1	43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	41	2	2

Variants in POU4F2

This is a list of pathogenic ClinVar variants found in the POU4F2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-146639152-G-A		not specified	Uncertain significance (May 16, 2024)
4-146639177-A-G		not specified	Uncertain significance (May 24, 2023)
4-146639186-C-A		not specified	Uncertain significance (Jun 10, 2024)
4-146639192-G-C		not specified	Uncertain significance (Mar 04, 2024)
4-146639214-A-G		not specified	Uncertain significance (Dec 10, 2024)
4-146639225-C-A		not specified	Uncertain significance (May 13, 2024)
4-146639231-A-G		not specified	Uncertain significance (Oct 07, 2024)
4-146639250-C-T		not specified	Uncertain significance (Mar 28, 2024)
4-146639260-C-G		not specified	Uncertain significance (Feb 14, 2023)
4-146639261-G-A		not specified	Uncertain significance (Apr 23, 2024)
4-146639276-T-A		not specified	Uncertain significance (Aug 19, 2021)
4-146639277-C-A		not specified	Uncertain significance (Aug 19, 2021)
4-146639277-C-G		not specified	Uncertain significance (Sep 30, 2024)
4-146639298-C-T		not specified	Uncertain significance (Aug 08, 2023)
4-146639312-G-A		not specified	Uncertain significance (Dec 03, 2024)
4-146639324-G-A		not specified	Likely benign (Aug 27, 2024)
4-146639360-A-C		not specified	Uncertain significance (Sep 25, 2024)
4-146639370-G-A		not specified	Uncertain significance (Jun 06, 2023)
4-146639405-A-C			Likely benign (Dec 01, 2022)
4-146639406-G-A		not specified	Uncertain significance (Feb 12, 2024)
4-146639424-C-T		not specified	Uncertain significance (Jan 03, 2024)
4-146639898-T-C		not specified	Uncertain significance (Apr 07, 2023)
4-146639962-C-A		not specified	Uncertain significance (Oct 26, 2022)
4-146639970-C-T		not specified	Uncertain significance (May 27, 2022)
4-146639995-C-A			Benign (Apr 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POU4F2	protein_coding	protein_coding	ENST00000281321	2	3582

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0748	0.878	125439	0	3	125442	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0789	229	232	0.985	0.0000105	2652
Missense in Polyphen		84	89.624	0.93724		981
Synonymous	-3.56	149	103	1.45	0.00000495	834
Loss of Function	1.68	3	8.20	0.366	3.53e-7	96

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000297	0.0000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000207	0.0000177
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells (PubMed:19266028, PubMed:23805044). Functions either as activator or repressor modulating the rate of target gene transcription through RNA polymerase II enzyme in a promoter-dependent manner (PubMed:19266028, PubMed:23805044). 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 (By similarity). {ECO:0000250|UniProtKB:Q63934, ECO:0000269|PubMed:19266028, ECO:0000269|PubMed:23805044}.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Regulation of TP53 Activity through Association with Co-factors;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Direct p53 effectors;Validated nuclear estrogen receptor alpha network (Consensus)

Recessive Scores

• pRec: 0.200

Intolerance Scores

• loftool: 0.0553
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.638
• hipred: Y
• hipred_score: 0.736
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.936

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pou4f2
• Phenotype: normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;MAPK cascade;spermatogenesis;axon guidance;heart development;sensory perception of sound;positive regulation of cardiac muscle cell apoptotic process;neuron differentiation;intracellular estrogen receptor signaling pathway;retinal ganglion cell axon guidance;cellular response to insulin stimulus;positive regulation of programmed cell death;negative regulation of DNA-binding transcription factor activity;negative regulation of cell differentiation;positive regulation of cell differentiation;positive regulation of osteoclast differentiation;positive regulation of axon extension;positive regulation of transcription by RNA polymerase II;positive regulation of glucose import;axon extension;neuromuscular process controlling balance;regulation of DNA-binding transcription factor activity;retina development in camera-type eye;cellular response to cytokine stimulus;cellular response to estradiol stimulus;cellular response to oxygen levels;intrinsic apoptotic signaling pathway by p53 class mediator;regulation of retinal ganglion cell axon guidance;regulation of signal transduction by p53 class mediator;negative regulation of amacrine cell differentiation;negative regulation of adipose tissue development;dorsal root ganglion development;positive regulation of transcription regulatory region DNA binding
• Cellular component: nucleus;nucleoplasm;transcription factor complex;nuclear euchromatin;cytoplasm;nuclear speck
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;p53 binding;transcription coactivator activity;transcription corepressor activity;promoter-specific chromatin binding