Human Gene Module / Chromosome 1 / CA6

CA6carbonic anhydrase VI

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 7
Rare Variants / Common Variants
2 / 0
Aliases
CA6, CA-VI,  GUSTIN,  MGC21256
Associated Syndromes
-
Chromosome Band
1p36.23
Associated Disorders
-
Relevance to Autism

Rare variants in the CA6 gene have been identified with autism (Bucan et al., 2009).

Molecular Function

The protein encoded by this gene is one of several isozymes of carbonic anhydrase.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CA6 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Decreased parotid saliva gustin/carbonic anhydrase VI secretion: an enzyme disorder manifested by gustatory and olfactory dysfunction Henkin RI , et al. (2000) No -
2 Recent Recommendation cAMP and cGMP in human parotid saliva: relationships to taste and smell dysfunction, gender, and age Henkin RI , et al. (2007) No -
3 Primary Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes Bucan M , et al. (2009) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Highly Cited Gustin concentration changes relative to salivary zinc and taste in humans Shatzman AR and Henkin RI (1981) No -
6 Highly Cited Sequence of bovine carbonic anhydrase VI: potential recognition sites for N-acetylgalactosaminyltransferase Jiang W , et al. (1996) No -
7 Highly Cited Gustin from human parotid saliva is carbonic anhydrase VI Thatcher BJ , et al. (1998) No -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - Multiplex 19557195 Bucan M , et al. (2009)
c.351G>A p.Ala117%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

One report describes multiple exonic events in cases but none in controls (Bucan M et al., 2009). None of the variants confirmed beyond arrays, and statistical support is lacking (nominal only). 50% of the events were inherited from a parent.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

One report describes multiple exonic events in cases but none in controls (Bucan M et al., 2009). None of the variants confirmed beyond arrays, and statistical support is lacking (nominal only). 50% of the events were inherited from a parent.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

One report describes multiple exonic events in cases but none in controls (Bucan M et al., 2009). None of the variants confirmed beyond arrays, and statistical support is lacking (nominal only). 50% of the events were inherited from a parent.

Reports Added
[New Scoring Scheme]
7/1/2014
No data
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4

Increased from No data to 4

Description

One report describes multiple exonic events in cases but none in controls (Bucan M et al., 2009). None of the variants confirmed beyond arrays, and statistical support is lacking (nominal only). 50% of the events were inherited from a parent.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

One report describes multiple exonic events in cases but none in controls (Bucan M et al., 2009). None of the variants confirmed beyond arrays, and statistical support is lacking (nominal only). 50% of the events were inherited from a parent.

Krishnan Probability Score

Score 0.44735373605645

Ranking 12605/25841 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 0.0080236207649399

Ranking 10180/18225 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 0.61725234052212

Ranking 768/18665 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
Larsen Cumulative Evidence Score

Score 8

Ranking 218/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.20446090338111

Ranking 15523/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
B4GALNT3 beta-1,4-N-acetyl-galactosaminyl transferase 3 Human Protein Modification 283358 Q6L9W6
B4GALNT4 beta-1,4-N-acetyl-galactosaminyl transferase 4 Human Protein Modification 338707 Q76KP1
KRT31 keratin 31 Human Protein Binding 3881 Q15323
NOTCH2NL notch 2 N-terminal like Human Protein Binding 388677 Q7Z3S9
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