Human Gene Module / Chromosome 2 / POU3F3

POU3F3POU class 3 homeobox 3

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
1 / 5
Rare Variants / Common Variants
40 / 0
Aliases
POU3F3, BRN1,  OTF8,  brain-1,  oct-8
Associated Syndromes
-
Chromosome Band
2q12.1
Associated Disorders
ASD
Relevance to Autism

Snijders Blok et al., 2019 reported 19 individuals with heterozygous disruptions of the POU3F3 gene, all of whom presented with developmental delays and/or intellectual disability and impaired speech and language skills; furthermore, many individuals with POU3F3 disruptions displayed autistic features, with 7/19 individuals (37%) receiving a formal diagnosis of autism spectrum disorder (ASD).

Molecular Function

This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to POU3F3 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De Novo Variants Disturbing the Transactivation Capacity of POU3F3 Cause a Characteristic Neurodevelopmental Disorder Snijders Blok L , et al. (2019) No ASD
2 Support - Torun D et al. (2021) No Autistic features
3 Support - Zhou X et al. (2022) Yes -
4 Recent Recommendation - Rossi A et al. (2023) No ASD or autistic features, ADHD, epilepsy/seizures
5 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (40)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.805G>T p.Glu269Ter stop_gained De novo - - 37165752 Rossi A et al. (2023)
c.982C>T p.Gln328Ter stop_gained Unknown - - 37165752 Rossi A et al. (2023)
c.1240G>T p.Glu414Ter stop_gained De novo - - 37165752 Rossi A et al. (2023)
c.997C>T p.Arg333Cys missense_variant De novo - - 37165752 Rossi A et al. (2023)
c.1009G>A p.Gly337Ser missense_variant De novo - - 37165752 Rossi A et al. (2023)
c.1019A>C p.Gln340Pro missense_variant De novo - - 37165752 Rossi A et al. (2023)
c.1070A>G p.Gln357Arg missense_variant De novo - - 37165752 Rossi A et al. (2023)
c.1319C>A p.Ala440Asp missense_variant De novo - - 37165752 Rossi A et al. (2023)
c.1328T>C p.Leu443Pro missense_variant De novo - - 37165752 Rossi A et al. (2023)
c.1360T>A p.Phe454Ile missense_variant De novo - - 37165752 Rossi A et al. (2023)
c.1284C>A p.Cys428Ter stop_gained De novo - - 31303265 Snijders Blok L , et al. (2019)
c.1303_1305del p.Glu435del inframe_deletion De novo - - 37165752 Rossi A et al. (2023)
c.196dup p.Asp66GlyfsTer574 frameshift_variant De novo - - 37165752 Rossi A et al. (2023)
c.823del p.His275ThrfsTer94 frameshift_variant De novo - - 37165752 Rossi A et al. (2023)
c.189C>A p.Tyr63Ter stop_gained De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1018_1019delinsTT p.Gln340Leu missense_variant De novo - - 33645921 Torun D et al. (2021)
c.1182dup p.Thr395HisfsTer245 frameshift_variant De novo - - 37165752 Rossi A et al. (2023)
c.71C>A p.Ser24Ter stop_gained Familial Maternal Multiplex 37165752 Rossi A et al. (2023)
c.668C>A p.Ser223Ter stop_gained De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1240G>T p.Glu414Ter stop_gained De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1147_1155del p.Trp383_Glu385del inframe_deletion De novo - - 37165752 Rossi A et al. (2023)
c.398_407del p.Pro133HisfsTer14 frameshift_variant De novo - - 37165752 Rossi A et al. (2023)
c.1234_1244del p.Ser412GlufsTer224 frameshift_variant De novo - - 37165752 Rossi A et al. (2023)
c.1085G>T p.Arg362Leu missense_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1219C>G p.Arg407Gly missense_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1220G>T p.Arg407Leu missense_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1367A>G p.Asn456Ser missense_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.576_611dup p.Ala193_Ala204dup inframe_insertion De novo - Simplex 35982159 Zhou X et al. (2022)
c.398_407del p.Pro133HisfsTer14 frameshift_variant De novo - - 39039281 Axel Schmidt et al. (2024)
c.617_632delinsCCC p.Leu206ProfsTer21 frameshift_variant De novo - - 37165752 Rossi A et al. (2023)
c.353del p.Ala118GlyfsTer32 frameshift_variant Unknown Not maternal - 37165752 Rossi A et al. (2023)
c.992_1006del p.Gln331_Lys335del inframe_deletion De novo - - 31303265 Snijders Blok L , et al. (2019)
c.366_367del p.Trp122CysfsTer517 frameshift_variant De novo - - 31303265 Snijders Blok L , et al. (2019)
c.524del p.Pro175ArgfsTer56 frameshift_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.774del p.Leu259TrpfsTer110 frameshift_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1197del p.Ile400SerfsTer16 frameshift_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.246_267del p.Met82IlefsTer3 frameshift_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.436_437dup p.Pro147AlafsTer4 frameshift_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.196_197delinsT p.Asp66SerfsTer26 frameshift_variant De novo - Simplex 31303265 Snijders Blok L , et al. (2019)
c.1352_1362del p.Arg451LeufsTer185 frameshift_variant Familial Maternal Simplex 31303265 Snijders Blok L , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Snijders Blok et al., 2019 reported 19 individuals with heterozygous disruptions of the POU3F3 gene, all of whom presented with developmental delays and/or intellectual disability and impaired speech and language skills; furthermore, many individuals with POU3F3 disruptions displayed autistic features, with 7/19 individuals (37%) receiving a formal diagnosis of autism spectrum disorder (ASD).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Snijders Blok et al., 2019 reported 19 individuals with heterozygous disruptions of the POU3F3 gene, all of whom presented with developmental delays and/or intellectual disability and impaired speech and language skills; furthermore, many individuals with POU3F3 disruptions displayed autistic features, with 7/19 individuals (37%) receiving a formal diagnosis of autism spectrum disorder (ASD).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.49684754660786

Ranking 2495/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
Sanders TADA Score

Score 0.92930001970624

Ranking 11132/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score -0.21095498685503

Ranking 15662/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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