Human Gene Module / Chromosome 19 / PRR12

PRR12proline rich 12

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
5 / 10
Rare Variants / Common Variants
37 / 0
Aliases
PRR12, KIAA1205
Associated Syndromes
Neuroocular syndrome, Neuroocular syndrome, DD
Chromosome Band
19q13.33
Associated Disorders
ADHD, ASD
Relevance to Autism

A de novo translocation disrupting the PRR12 gene was identified in a female patient presenting with intellectual disability, seizures, and behavioral problems in Crdova-Fletes et al., 2015. Three de novo potentially loss-of-function (LoF) variants in the PRR12 gene were identified in patients presenting with intellectual disability, iris abnormalities, and dysmorphic features in Leduc et al., 2018; two of these patients were also diagnosed with ASD by formal testing.

Molecular Function

This gene encodes a proline-rich protein that contains two A-T hook DNA binding domains. Enriched expression of this gene in embryonic mouse brain suggests that this gene may play a role in nervous system development.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PRR12 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support A de novo t(10;19)(q22.3;q13.33) leads to ZMIZ1/PRR12 reciprocal fusion transcripts in a girl with intellectual disability and neuropsychiatric alterations Crdova-Fletes C , et al. (2015) No Behavioral abnormalities
2 Primary De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities Leduc MS , et al. (2018) No ASD, ADHD
3 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Support - Reis LM et al. (2021) No DD, ID, learning difficulties
5 Support - Chowdhury F et al. (2021) No ASD or autistic features, ID, epilepsy/seizures
6 Support - Woodbury-Smith M et al. (2022) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Support - Alessia Muscò et al. (2024) No -
9 Support - Soo-Whee Kim et al. (2024) Yes -
10 Support - Afif Ben-Mahmoud et al. (2024) Yes DD
Rare Variants   (37)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 33824499 Chowdhury F et al. (2021)
- - translocation De novo - - 26163108 Crdova-Fletes C , et al. (2015)
- - translocation De novo - Simplex 26163108 Crdova-Fletes C , et al. (2015)
c.1918G>T p.Glu640Ter stop_gained De novo - - 29556724 Leduc MS , et al. (2018)
c.790C>T p.Gln264Ter stop_gained De novo - - 33824499 Chowdhury F et al. (2021)
c.4891-2A>G - splice_site_variant De novo - - 33824499 Chowdhury F et al. (2021)
c.3395C>G p.Pro1132Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3991G>A p.Ala1331Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3505C>T p.Arg1169Trp missense_variant De novo - - 33824499 Chowdhury F et al. (2021)
c.1200C>T p.Ala400= synonymous_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.2746C>A p.Pro916Thr missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2755C>T p.Gln919Ter stop_gained De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.3958C>T p.Arg1320Ter stop_gained De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.2678C>T p.Ala893Val missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.5624-2A>G - splice_site_variant Familial Maternal Simplex 33314030 Reis LM et al. (2021)
c.4174C>T p.Arg1392Ter stop_gained De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.334dup p.Gln112ProfsTer69 frameshift_variant De novo - - 33824499 Chowdhury F et al. (2021)
c.5909T>C p.Leu1970Pro missense_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.425_431dup p.Ser146ValfsTer37 frameshift_variant De novo - - 29556724 Leduc MS , et al. (2018)
c.4768dup p.Leu1590ProfsTer10 frameshift_variant De novo - - 33824499 Chowdhury F et al. (2021)
c.677dup p.Tyr227LeufsTer41 frameshift_variant De novo - Simplex 33314030 Reis LM et al. (2021)
c.3273del p.Lys1092ArgfsTer131 frameshift_variant De novo - - 33824499 Chowdhury F et al. (2021)
c.2045del p.Gly682AspfsTer44 frameshift_variant De novo - Simplex 33314030 Reis LM et al. (2021)
c.2054G>C p.Gly685Ala missense_variant De novo - Simplex 39519104 Afif Ben-Mahmoud et al. (2024)
c.4691_4694del p.Glu1564AlafsTer83 frameshift_variant De novo - - 29556724 Leduc MS , et al. (2018)
c.2353_2360del p.Ala785ProfsTer2 frameshift_variant Unknown - Simplex 33314030 Reis LM et al. (2021)
c.2398dup p.Gln800ProfsTer26 frameshift_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.2824del p.Glu942ArgfsTer88 frameshift_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.1232C>A p.Ser411Ter stop_gained Unknown Not maternal Multiplex 33824499 Chowdhury F et al. (2021)
c.3273delC p.Lys1092ArgfsTer131 frameshift_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.3224del p.Thr1075AsnfsTer148 frameshift_variant Unknown - Multiplex 33824499 Chowdhury F et al. (2021)
c.2236_2237del p.Val746CysfsTer43 frameshift_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.3273del p.Lys1092ArgfsTer131 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2732_2744del p.Gly911AlafsTer115 frameshift_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.3009_3028dup p.Leu1010ProfsTer27 frameshift_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
c.1521T>G p.Tyr507Ter stop_gained De novo - Multiplex (monozygotic twins) 33824499 Chowdhury F et al. (2021)
c.4674_4676delinsGC p.Cys1558TrpfsTer90 frameshift_variant De novo - Simplex 33824499 Chowdhury F et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

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."

4/1/2022
S
icon
1

Increased from S to 1

1/1/2020
S
icon
S

Increased from S to S

Description

A de novo translocation disrupting the PRR12 gene was identified in a female patient presenting with intellectual disability, seizures, and behavioral problems in Crdova-Fletes et al., 2015. Three de novo potentially loss-of-function (LoF) variants in the PRR12 gene were identified in patients presenting with intellectual disability, iris abnormalities, and dysmorphic features in Leduc et al., 2018; two of these patients were also diagnosed with ASD by formal testing.

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
S
icon
S

Increased from S to S

New Scoring Scheme
Description

A de novo translocation disrupting the PRR12 gene was identified in a female patient presenting with intellectual disability, seizures, and behavioral problems in Crdova-Fletes et al., 2015. Three de novo potentially loss-of-function (LoF) variants in the PRR12 gene were identified in patients presenting with intellectual disability, iris abnormalities, and dysmorphic features in Leduc et al., 2018; two of these patients were also diagnosed with ASD by formal testing.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.48621619685685

Ranking 7222/25841 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
ExAC Score

Score 0.99996957688368

Ranking 542/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94789781294533

Ranking 17463/18665 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 0.33721170159193

Ranking 2180/20870 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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