POU3F3

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

Basic information

Region (hg38): 2:104853287-104858574

Links

ENSG00000198914 ∙ NCBI:5455 ∙ OMIM:602480 ∙ HGNC:9216 ∙ Uniprot:P20264 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• snijders blok-fisher syndrome (Strong), mode of inheritance: AD
• snijders blok-fisher syndrome (Strong), mode of inheritance: AD
• snijders blok-fisher syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Snijders Block-Fisher syndrome	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	31303265

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POU3F3 gene.

• Snijders blok-fisher syndrome (4 variants)
• not provided (2 variants)
• Inborn genetic diseases (2 variants)
• Developmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POU3F3 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				13	1	14
missense	1	10	70	1		82
nonsense		5	1			6
start loss			1			1
frameshift	8	6				14
inframe indel		2	2	6	1	11
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	9	23	74	20	3

Variants in POU3F3

This is a list of pathogenic ClinVar variants found in the POU3F3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-104855511-A-G			Uncertain significance (May 02, 2022)
2-104855518-C-G			Uncertain significance (May 25, 2022)
2-104855531-C-T		POU3F3-related disorder	Likely benign (Nov 01, 2024)
2-104855585-C-G		Inborn genetic diseases	Uncertain significance (Mar 21, 2023)
2-104855592-G-A		POU3F3-related disorder	Uncertain significance (Feb 15, 2023)
2-104855597-T-C		POU3F3-related disorder	Likely benign (Apr 23, 2021)
2-104855600-C-T			Benign (Apr 01, 2022)
2-104855608-G-A		Snijders blok-fisher syndrome	Uncertain significance (Feb 09, 2021)
2-104855611-G-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2024)
2-104855611-G-T			Uncertain significance (Jan 06, 2024)
2-104855612-T-TGGC			Likely benign (Sep 01, 2024)
2-104855624-CGGCGGCGGG-C		Inborn genetic diseases	Likely benign (Nov 02, 2022)
2-104855627-CGGCGGGGGCGGCGCAGGG-C			Likely benign (Apr 01, 2023)
2-104855630-C-G			Likely benign (Nov 01, 2023)
2-104855630-CG-C		Inborn genetic diseases	Likely pathogenic (Jun 21, 2019)
2-104855630-C-CGGG		Inborn genetic diseases	Benign (Aug 17, 2023)
2-104855647-G-C		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
2-104855648-C-G			Likely benign (Oct 01, 2024)
2-104855667-C-T		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
2-104855673-A-C		Snijders blok-fisher syndrome	Uncertain significance (Jan 29, 2023)
2-104855674-G-C			Uncertain significance (Apr 08, 2022)
2-104855700-C-CG		Snijders blok-fisher syndrome	Pathogenic (Dec 31, 2020)
2-104855701-G-T		POU3F3-related disorder	Uncertain significance (Sep 02, 2023)
2-104855704-G-A			Uncertain significance (Apr 26, 2023)
2-104855706-G-A		Inborn genetic diseases	Likely benign (Sep 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POU3F3	protein_coding	protein_coding	ENST00000361360	1	4961

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.883	0.116	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.04	63	177	0.356	0.00000821	3161
Missense in Polyphen		5	59.109	0.084589		753
Synonymous	-0.602	92	84.9	1.08	0.00000412	1059
Loss of Function	2.45	0	6.98	0.00	3.04e-7	103

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: Transcription factor that acts synergistically with SOX11 and SOX4. Plays a role in neuronal development. Is implicated in an enhancer activity at the embryonic met- mesencephalic junction; the enhancer element contains the octamer motif (5'-ATTTGCAT-3') (By similarity). {ECO:0000250}.

Haploinsufficiency Scores

• pHI: 0.487
• ghis: 0.641

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.927

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pou3f3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; skeleton phenotype; renal/urinary system phenotype; hearing/vestibular/ear 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); 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: central nervous system development;excretion;positive regulation of cell population proliferation;positive regulation of gene expression;cerebral cortex radially oriented cell migration;forebrain ventricular zone progenitor cell division;negative regulation of apoptotic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;chemical homeostasis;metanephric ascending thin limb development;metanephric macula densa development;metanephric thick ascending limb development;metanephric loop of Henle development;metanephric DCT cell differentiation
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;sequence-specific DNA binding;HMG box domain binding