Human Gene Module / Chromosome 2 / KLF7

KLF7Kruppel like factor 7

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
7 / 14
Rare Variants / Common Variants
17 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
2q33.3
Associated Disorders
-
Relevance to Autism

KLF7 has been proposed to be a possible candidate gene for phenotypes associated with 2q33.3-q34 deletions, incuding autism spectrum disorder/autistic features (Courtens et al., 1997; Pescucci et al., 2003; Bisgaard et al., 2006; Brandau et al., 2008; Rosenfeld et al., 2010; Jang et al., 2015). Powis et al., 2017 reported 4 unrelated individuals with de novo and potentially damaging missense variants in the KLF7 gene who shared similar clinical features, including developmental delay/intellectual disability, hypotonia, feeding/swallowing issues, psychiatric features, and neuromuscular symptoms; one of these individuals was also diagnosed with autism spectrum disorder. Additional rare de novo non-coding variants in this gene have been observed in ASD probands (Yuen et al., 2016; Yuen et al., 2017; Turner et al., 2017). Tian et al., 2022 reported that klf7 +/- mice exhibited a number of ASD-related behaviors, including deficits in social interaction and repetitive behavior.

Molecular Function

The protein encoded by this gene is a member of the Kruppel-like transcriptional regulator family. Members in this family regulate cell proliferation, differentiation and survival and contain three C2H2 zinc fingers at the C-terminus that mediate binding to GC-rich sites. This protein may contribute to the progression of type 2 diabetes by inhibiting insulin expression and secretion in pancreatic beta-cells and by deregulating adipocytokine secretion in adipocytes. This protein also plays a critical role in neuronal morphogenesis and the survival of sensory neurons.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KLF7 (14 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Chromosome 2 deletion encompassing the MAP2 gene in a patient with autism and Rett-like features Pescucci C , et al. (2004) No Autistic features, stereotypy
2 Support - Bisgaard AM et al. (2006) No Autistic features
3 Support - Brandau DT et al. (2008) No Autistic behavior
4 Support Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders Rosenfeld JA , et al. (2010) Yes -
5 Support - Jang DH et al. (2015) No Autistic features, stereotypy
6 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
7 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
8 Support Genomic Patterns of De Novo Mutation in Simplex Autism Turner TN et al. (2017) Yes -
9 Primary - Powis Z et al. (2018) No ASD, ADD
10 Recent Recommendation - Tian H et al. (2022) Yes -
11 Support - Zhou X et al. (2022) Yes -
12 Support - Tian H et al. (2022) Yes -
13 Support - Hong W et al. (2023) No -
14 Support - Courtens W et al. (1997) No -
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 9286460 Courtens W et al. (1997)
- - copy_number_loss De novo - - 18203195 Brandau DT et al. (2008)
- - copy_number_loss De novo - - 14986829 Pescucci C , et al. (2004)
- - copy_number_loss De novo - - 16955412 Bisgaard AM et al. (2006)
- - copy_number_loss Unknown - - 20808228 Rosenfeld JA , et al. (2010)
- - copy_number_loss De novo - Simplex 25899208 Jang DH et al. (2015)
c.424C>G p.Pro142Ala missense_variant De novo - - 35982159 Zhou X et al. (2022)
n.515-11604G>A - intron_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
n.575+4675G>A - intron_variant De novo - Simplex 28965761 Turner TN et al. (2017)
n.575+7470G>T - intron_variant De novo - Simplex 28965761 Turner TN et al. (2017)
n.576-4471G>A - intron_variant De novo - Simplex 28965761 Turner TN et al. (2017)
c.*1606C>T - 3_prime_UTR_variant De novo - Simplex 28965761 Turner TN et al. (2017)
c.410C>T p.Thr137Met missense_variant De novo - Simplex 29251763 Powis Z et al. (2018)
c.415C>T p.Pro139Ser missense_variant De novo - Simplex 29251763 Powis Z et al. (2018)
c.790G>A p.Asp264Asn missense_variant De novo - Simplex 29251763 Powis Z et al. (2018)
c.103-10377_103-10367del - intron_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.531+4993_531+4995del - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.57049209259791

Ranking 915/25841 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 0.92993070889515

Ranking 2933/18225 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 0.82870279974305

Ranking 2817/18665 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 0.18577626319947

Ranking 4502/20870 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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