POU4F1

protein-coding

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

Gene summary

This gene encodes a member of the POU-IV class of neural transcription factors. This protein is expressed in a subset of retinal ganglion cells and may be involved in the developing sensory nervous system. This protein may also promote the growth of cervical tumors. A translocation of this gene is associated with some adult acute myeloid leukemias. [provided by RefSeq, Mar 2012]

Previous symbols:

BRN3A

MANE transcript

NM_006237.4

Inheritance

ClinVar variants

P:9U:84B:33

Top phenotype

Ataxia, intention tremor, and hypotonia syndrome, childhood-onset

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr13:78,598,362-78,603,552

External References & Databases

Ensembl (ENSG00000152192)

Transcript & Mutation Effects

hg38 • Region Span ~5.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ataxia, intention tremor, and hypotonia syndrome, childhood-onsetSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859158

Submitter: PanelApp Australia

ataxia, intention tremor, and hypotonia syndrome, childhood-onsetSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859158

Submitter: Labcorp Genetics (formerly Invitae)

ataxia, intention tremor, and hypotonia syndrome, childhood-onsetSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859158

Submitter: G2P

Clinical Genomic Database (CGD)

Ataxia, intention tremor, and hypotonia syndrome, childhood-onsetAD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 33783914

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POU4F1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 60

Ataxia, intention tremor, and hypotonia syndrome, childhood-onsetTotal: 13

POU4F1-related disorderTotal: 7

Inborn genetic diseasesTotal: 2

Cerebellar dysfunction with variable cognitive and behavioral abnormalitiesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006237.4. 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				28 clinvar		28
missense	1 clinvar		71 clinvar	4 clinvar	1 clinvar	77
nonsense			3 clinvar			3
start loss						0
frameshift	3 clinvar	5 clinvar	9 clinvar			17
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	5	84	32	1	126

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_006237.4	RefSeq	NP_006228.3	2	MANE Select
ENST00000377208.7	Ensembl	ENSP00000366413.4	2	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MECP2 and Associated Rett Syndrome
Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription
Regulation of TP53 Activity through Association with Co-factors

Biological Process

negative regulation of transcription by RNA polymerase II
suckling behavior
ventricular compact myocardium morphogenesis
axonogenesis
synapse assembly

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

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
cytoplasm
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377208
Coding exons: 2
Length: 5177
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	2.45	77	166	0.464	0.00000746	2656
Missense (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

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: 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}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.966

Gene Damage Prediction

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