POU6F2

protein-coding

POU class 6 homeobox 2, the group of POU class homeoboxes and pseudogenes

Gene summary

This gene encodes a member of the POU protein family characterized by the presence of a bipartite DNA binding domain, consisting of a POU-specific domain and a homeodomain, separated by a variable polylinker. The DNA binding domain may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner. The POU family members are transcriptional regulators, many of which are known to control cell type-specific differentiation pathways. This gene is a tumor suppressor involved in Wilms tumor (WT) predisposition. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

MANE transcript

NM_001370959.1

Inheritance

ClinVar variants

P:2U:112B:36

Top phenotype

Wilms tumor 5

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr7:38,977,909-39,493,095

External References & Databases

Ensembl (ENSG00000106536)

Transcript & Mutation Effects

hg38 • Region Span ~515.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Wilms tumor 5LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0011112

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Wilms tumor 5AD

Manifestation: Oncologic

Intervention: Oncologic

Rationale: Individuals may be at high risk for Wilms tumor, and surveillance may allow early diagnosis and treatment

Comments: Germline variants can predispose to disease due to loss of heterozygosity

Refs: 11284034

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POU6F2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 115

not providedTotal: 25

POU6F2-related disorderTotal: 17

Hypogonadotropic hypogonadismTotal: 10

Wilms tumor 5Total: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001370959.1. 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				20 clinvar	1 clinvar	21
missense	1 clinvar		112 clinvar	9 clinvar	4 clinvar	126
nonsense	1 clinvar					1
start loss						0
frameshift				2 clinvar		2
splice donor/acceptor (+/-2bp)						0
Total	2	0	112	31	5	150

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001370959.1	RefSeq	NP_001357888.1	10	MANE Select
ENST00000518318.7	Ensembl	ENSP00000430514.3	10	MANE Select
NM_001166018.2	RefSeq	NP_001159490.1	10	Standard
NM_007252.4	RefSeq	NP_009183.3	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
ganglion mother cell fate determination
central nervous system development

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403058
Coding exons: 10
Length: 515097
Individuals with no LoFs: 125361
Homozygous LoFs: 1
Heterozygous LoFs: 247
Defined: 125609
p: 0.000988

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.455	361	386	0.935	0.0000218	4427
Missense (PolyPhen)		52	53.591	0.97031		578
Synonymous	-0.220	174	170	1.02	0.0000107	1470
Loss of Function	3.52	11	32.7	0.336	0.00000165	317

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00061	0.00035	rare
Ashkenazi Jewish	0.0014	0.00070	notable
East Asian	0.00011	0.00011	rare
Finnish	0.0030	0.0011	notable
European (Non-Finnish)	0.00084	0.00052	rare
South Asian	0.0083	0.0045	notable
Other	0.0020	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells. Recognizes and binds to the DNA sequence 5'-ATGCAAAT-3'. Isoform 1 does not bind DNA.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.110
RVIS EVS: -0.55
RVIS percentile EVS: 19.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.207

Gene Damage Prediction

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