Human Gene Module / Chromosome 14 / UNC79

UNC79unc-79 homolog, NALCN channel complex subunit

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 9
Rare Variants / Common Variants
22 / 0
Aliases
UNC79, KIAA1409
Associated Syndromes
-
Chromosome Band
14q32.12
Associated Disorders
-
Relevance to Autism

A de novo loss-of-function (LoF) variant in the UNC79 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A second LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Molecular Function

This gene encodes for a component of the NALCN sodium channel complex, a cation channel activated either by neuropeptides substance P or neurotensin that controls neuronal excitability and that is responsible for Na(+) leak currents. The protein encoded by this gene, along with UNC80, is an accessory subunit of the NALCN channel that contributes to the Ca(2+) sensitivity of the channel.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to UNC79 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder Krupp DR , et al. (2017) Yes -
3 Support Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders Schluth-Bolard C , et al. (2019) No Behavioral abnormalities
4 Support - Zhou J et al. (2019) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
6 Recent Recommendation - Chen X et al. (2021) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Recent Recommendation - Bayat A et al. (2023) No ADHD, epilepsy/seizures, autistic features, stereo
9 Support - Sheth F et al. (2023) Yes DD, ID
Rare Variants   (22)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - - 30923172 Schluth-Bolard C , et al. (2019)
C>T - intergenic_variant De novo - Simplex 31133750 Zhou J et al. (2019)
c.62G>A p.Arg21Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1580T>C p.Val527Ala missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.6005C>T p.Thr2002Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3754+1G>A - splice_site_variant De novo - Simplex 37183800 Bayat A et al. (2023)
c.5475G>A p.Gly1825%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.6651C>T p.Pro2217%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.7815+3A>T - splice_region_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2070C>A p.Cys690Ter stop_gained De novo - Simplex 37183800 Bayat A et al. (2023)
c.5326C>T p.Gln1776Ter stop_gained De novo - Simplex 37183800 Bayat A et al. (2023)
c.6315_6317del p.Ala2106del inframe_deletion De novo - - 35982159 Zhou X et al. (2022)
c.6208C>T p.Arg2070Ter stop_gained De novo - Simplex 28867142 Krupp DR , et al. (2017)
c.4781G>T p.Gly1594Val missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.5475G>A p.Gly1825%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.432A>G p.Leu144%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.5371del p.Leu1791Ter frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.149del p.Leu50CysfsTer15 frameshift_variant De novo - Simplex 37183800 Bayat A et al. (2023)
c.2961dup p.Cys988MetfsTer55 frameshift_variant De novo - Simplex 37183800 Bayat A et al. (2023)
c.4955T>C p.Phe1652Ser missense_variant Familial Maternal Simplex 37543562 Sheth F et al. (2023)
c.6119del p.Val2040GlyfsTer14 frameshift_variant De novo - Simplex 37183800 Bayat A et al. (2023)
c.5535_5536dup p.Asn1846ArgfsTer97 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo loss-of-function (LoF) variant in the UNC79 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A second LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A de novo loss-of-function (LoF) variant in the UNC79 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A second LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function (LoF) variant in the UNC79 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A second LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
4/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function (LoF) variant in the UNC79 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A second LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Reports Added
[Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with develop...2019]
10/1/2017
icon
3

Increased from to 3

Description

A de novo loss-of-function (LoF) variant in the UNC79 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A second LoF variant in this gene was identified as a mosaic mutation in another ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Krishnan Probability Score

Score 0.49591580887091

Ranking 2749/25841 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 0.99999999997391

Ranking 56/18225 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 0.7651212907239

Ranking 1716/18665 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 -0.19429900128085

Ranking 15291/20870 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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