POU4F1

POU class 4 homeobox 1, the group of POU class homeoboxes and pseudogenes

Basic information

Region (hg38): 13:78598362-78603552

Previous symbols: [ "BRN3A" ]

Links

ENSG00000152192 ∙ NCBI:5457 ∙ OMIM:601632 ∙ HGNC:9218 ∙ Uniprot:Q01851 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ataxia, intention tremor, and hypotonia syndrome, childhood-onset (Strong), mode of inheritance: AD
• ataxia, intention tremor, and hypotonia syndrome, childhood-onset (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ataxia, intention tremor, and hypotonia syndrome, childhood-onset	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	33783914

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POU4F1 gene.

• Ataxia, intention tremor, and hypotonia syndrome, childhood-onset (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POU4F1 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				9		9
missense			22	3		25
nonsense			1			1
start loss						0
frameshift	1	1	3			5
inframe indel			2	2	2	6
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding						0
Total	1	1	28	14	2

Variants in POU4F1

This is a list of pathogenic ClinVar variants found in the POU4F1 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-78601441-G-A		Ataxia, intention tremor, and hypotonia syndrome, childhood-onset	Uncertain significance (Oct 09, 2024)
13-78601484-G-C		not specified	Uncertain significance (Jun 01, 2023)
13-78601491-T-C		not specified	Uncertain significance (Apr 19, 2024)
13-78601553-G-A			Likely benign (Oct 01, 2024)
13-78601570-A-G		Inborn genetic diseases	Uncertain significance (Jan 24, 2019)
13-78601636-G-A		not specified	Uncertain significance (Nov 14, 2023)
13-78601637-C-T			Likely benign (Feb 01, 2023)
13-78601644-AT-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2019)
13-78601654-G-T		not specified	Uncertain significance (May 05, 2023)
13-78601733-C-T		POU4F1-related disorder	Likely benign (Sep 21, 2024)
13-78601742-C-G		not specified	Uncertain significance (Nov 09, 2024)
13-78601758-T-C		Ataxia, intention tremor, and hypotonia syndrome, childhood-onset	Pathogenic (Jun 08, 2021)
13-78601787-G-C			Likely benign (Oct 01, 2023)
13-78601825-C-A		not specified	Uncertain significance (Oct 30, 2023)
13-78601829-C-T			Likely benign (Mar 01, 2024)
13-78601835-G-C			Uncertain significance (Jun 12, 2024)
13-78601877-G-A		POU4F1-related disorder	Likely benign (Sep 29, 2023)
13-78601895-G-C		not specified	Uncertain significance (Nov 18, 2023)
13-78601922-G-A			Likely benign (Feb 01, 2023)
13-78601923-C-T		not specified	Uncertain significance (Mar 14, 2023)
13-78601969-C-A		POU4F1-related disorder • not specified	Conflicting classifications of pathogenicity (Oct 01, 2024)
13-78601996-C-T		Ataxia, intention tremor, and hypotonia syndrome, childhood-onset	Uncertain significance (Oct 17, 2023)
13-78602027-G-T		not specified	Uncertain significance (Jan 23, 2024)
13-78602043-G-T		not specified	Uncertain significance (Oct 21, 2024)
13-78602045-C-T		not specified	Uncertain significance (May 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POU4F1	protein_coding	protein_coding	ENST00000377208	2	5177

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.888	0.111	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	77	166	0.464	0.00000746	2656
Missense in Polyphen		16	22.704	0.70472		294
Synonymous	-0.535	83	77.0	1.08	0.00000372	921
Loss of Function	2.47	0	7.10	0.00	3.05e-7	85

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Multifunctional transcription factor with different regions mediating its different effects. Acts by binding (via its C-terminal domain) to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes. Regulates the expression of specific genes involved in differentiation and survival within a subset of neuronal lineages. It has been shown that activation of some of these genes requires its N-terminal domain, maybe through a neuronal-specific cofactor. Ativates BCL2 expression and protects neuronal cells from apoptosis (via the N-terminal domain). Induces neuronal process outgrowth and the coordinate expression of genes encoding synaptic proteins. Exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. Stimulates the binding affinity of the nuclear estrogene receptor ESR1 to DNA estrogen response element (ERE), and hence modulates ESR1-induced transcriptional activity. May positively regulate POU4F2 and POU4F3. Regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Plays a role in TNFSF11-mediated terminal osteoclast differentiation. Negatively regulates its own expression interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site. {ECO:0000250|UniProtKB:P17208}.
• Pathway: MECP2 and Associated Rett Syndrome;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)

Haploinsufficiency Scores

• pHI: 0.779
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pou4f1
• Phenotype: 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); vision/eye phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;suckling behavior;ventricular compact myocardium morphogenesis;axonogenesis;synapse assembly;mesoderm development;heart development;positive regulation of gene expression;negative regulation of gene expression;cell migration in hindbrain;trigeminal nerve development;central nervous system neuron differentiation;habenula development;neuron projection development;positive regulation of apoptotic process;negative regulation of programmed cell death;negative regulation of neuron apoptotic process;positive regulation of osteoclast differentiation;positive regulation of transcription by RNA polymerase II;neuron fate specification;sensory system development;peripheral nervous system neuron development;regulation of neurogenesis;regulation of DNA-binding transcription factor activity;proprioception involved in equilibrioception;innervation;positive regulation of cell cycle arrest;cellular response to cytokine stimulus;cellular response to estradiol stimulus;intrinsic apoptotic signaling pathway by p53 class mediator;regulation of signal transduction by p53 class mediator;positive regulation of transcription regulatory region DNA binding;negative regulation of transcription elongation by RNA polymerase I
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm;neuron projection
• Molecular function: RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;single-stranded DNA binding;transcription coactivator activity;transcription corepressor activity;sequence-specific DNA binding;GTPase binding