Human Gene Module / Chromosome 6 / SNX14

SNX14Sorting nexin 14

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 11
Rare Variants / Common Variants
24 / 0
Aliases
SNX14, RGS-PX2
Associated Syndromes
-
Chromosome Band
6q14.3
Associated Disorders
DD/NDD, ID, ASD
Relevance to Autism

Biallelic variants in SNX14 were shown to cause a recessive syndrome in 12 families characterized by cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability; detailed clinical characterization of affected individuals found that 22/22 displayed delayed or absent social development, while 12/22 displayed autistic-like behavior (Akizu et al., 2015).

Molecular Function

This gene encodes a member of the sorting nexin family that plays a role in maintaining normal neuronal excitability and synaptic transmission and may be involved in several stages of intracellular trafficking.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SNX14 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome Thomas AC , et al. (2014) No -
2 Primary Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction Akizu N , et al. (2015) No Autistic features
3 Support Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease Karaca E , et al. (2015) No Microcephaly
4 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No DD, ID
5 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support - Mitani T et al. (2021) No -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Sanchis-Juan A et al. (2023) No -
10 Recent Recommendation - Kuokuo Li et al. (2024) Yes -
11 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (24)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.2563A>G p.Lys855Glu missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Both parents Simplex 26539891 Karaca E , et al. (2015)
c.86C>G p.Pro29Arg missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.1132+3_1132+6del - splice_site_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.2652A>T p.Pro884%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.335A>C p.His112Pro missense_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.915+5G>A - splice_site_variant Familial Both parents Simplex 25848753 Akizu N , et al. (2015)
- - copy_number_loss Familial Both parents Extended multiplex 25439728 Thomas AC , et al. (2014)
c.2722C>T p.Gln908Ter stop_gained Familial Both parents - 27848944 Trujillano D , et al. (2016)
c.428T>A p.Leu143Ter stop_gained Familial Both parents Simplex 25848753 Akizu N , et al. (2015)
c.1867+1G>T - splice_site_variant Familial Both parents Simplex 25439728 Thomas AC , et al. (2014)
c.1132C>T p.Arg378Ter stop_gained Familial Both parents Multiplex 25848753 Akizu N , et al. (2015)
c.2596C>T p.Gln866Ter stop_gained Familial Both parents Multiplex 25439728 Thomas AC , et al. (2014)
c.1867+1G>T - splice_site_variant Familial Both parents Simplex 27848944 Trujillano D , et al. (2016)
c.645dup p.Glu216ArgfsTer25 frameshift_variant Familial Both parents Simplex 25848753 Akizu N , et al. (2015)
c.2737_2743del p.Asp913Ter frameshift_variant Familial Both parents Multiplex 25848753 Akizu N , et al. (2015)
c.1486dup p.Arg496LysfsTer4 frameshift_variant Familial Both parents Simplex 26539891 Karaca E , et al. (2015)
c.645dup p.Glu216ArgfsTer25 frameshift_variant Familial Both parents Multiplex 25848753 Akizu N , et al. (2015)
c.1182del p.Lys395ArgfsTer22 frameshift_variant Familial Both parents Multiplex 25848753 Akizu N , et al. (2015)
c.809_813del p.Ile270ArgfsTer17 frameshift_variant Familial Both parents Simplex 25848753 Akizu N , et al. (2015)
c.686_687del p.Ala229GlufsTer32 frameshift_variant Familial Both parents Simplex 34582790 Mitani T et al. (2021)
c.1859_1860del p.Glu620ValfsTer7 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2643del p.Cys881Ter frameshift_variant Familial Both parents Extended multiplex 25848753 Akizu N , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Biallelic variants in SNX14 were shown to cause a recessive syndrome in 12 families characterized by cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability; detailed clinical characterization of affected individuals found that 22/22 displayed delayed or absent social development, while 12/22 displayed autistic-like behavior (Akizu et al., 2015). Biallelic variants in this gene were also responsible for intellectual disability, cerebellar atrophy, and ataxia in affected individuals from three separate families in PMID 25439728.

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

Biallelic variants in SNX14 were shown to cause a recessive syndrome in 12 families characterized by cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability; detailed clinical characterization of affected individuals found that 22/22 displayed delayed or absent social development, while 12/22 displayed autistic-like behavior (Akizu et al., 2015). Biallelic variants in this gene were also responsible for intellectual disability, cerebellar atrophy, and ataxia in affected individuals from three separate families in PMID 25439728.

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

Score remained at S

Description

Biallelic variants in SNX14 were shown to cause a recessive syndrome in 12 families characterized by cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability; detailed clinical characterization of affected individuals found that 22/22 displayed delayed or absent social development, while 12/22 displayed autistic-like behavior (Akizu et al., 2015). Biallelic variants in this gene were also responsible for intellectual disability, cerebellar atrophy, and ataxia in affected individuals from three separate families in PMID 25439728.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2016
S
icon
S

Score remained at S

Description

Biallelic variants in SNX14 were shown to cause a recessive syndrome in 12 families characterized by cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability; detailed clinical characterization of affected individuals found that 22/22 displayed delayed or absent social development, while 12/22 displayed autistic-like behavior (Akizu et al., 2015). Biallelic variants in this gene were also responsible for intellectual disability, cerebellar atrophy, and ataxia in affected individuals from three separate families in PMID 25439728.

Reports Added
[Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016]
1/1/2016
S
icon
S

Score remained at S

Description

Biallelic variants in SNX14 were shown to cause a recessive syndrome in 12 families characterized by cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability; detailed clinical characterization of affected individuals found that 22/22 displayed delayed or absent social development, while 12/22 displayed autistic-like behavior (Akizu et al., 2015). Biallelic variants in this gene were also responsible for intellectual disability, cerebellar atrophy, and ataxia in affected individuals from three separate families in PMID 25439728.

Reports Added
[Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction.2015] [Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome.2014] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015]
Krishnan Probability Score

Score 0.36620572627935

Ranking 23941/25841 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 6.7999502496968E-10

Ranking 16649/18225 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 0.48941571342886

Ranking 426/18665 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 -0.023824614039723

Ranking 9484/20870 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
C3AR1 C3a anaphylatoxin chemotactic receptor Human Protein Binding 719 Q16581
CNGA3 Cyclic nucleotide-gated cation channel alpha-3 Human Protein Binding 1261 Q16281
FSHR Follicle-stimulating hormone receptor Human Protein Binding 2492 P23945
Htr6 5-hydroxytryptamine (serotonin) receptor 6 Mouse Protein Binding 15565 Q9R1C8
PCDHGA5 Protocadherin gamma-A5 Human Protein Binding 56110 Q9Y5G8-2
SLC17A2 Sodium-dependent phosphate transport protein 3 Human Protein Binding 10246 O00624-2
ZNRF4 Zinc/RING finger protein 4 Human Protein Binding 148066 Q8WWF5
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