Human Gene Module / Chromosome 9 / MLANA

MLANAmelan-A

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
3 / 0
Aliases
MLANA, MART-1,  MART1
Associated Syndromes
-
Chromosome Band
9p24.1
Associated Disorders
-
Relevance to Autism

A de novo nonsense variant in the MLANA gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified MLANA as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Molecular Function

Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the formation of stage II melanosomes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MLANA (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Recent Recommendation Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.76G>T p.Glu26Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.151C>T p.Arg51Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.32_42del p.Gly11GlufsTer11 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo nonsense variant in the MLANA gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified MLANA as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

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

A de novo nonsense variant in the MLANA gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified MLANA as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo nonsense variant in the MLANA gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified MLANA as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Reports Added
[New Scoring Scheme]
7/1/2019
icon
4

Increased from to 4

Description

A de novo nonsense variant in the MLANA gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified MLANA as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Krishnan Probability Score

Score 0.54027643446132

Ranking 1443/25841 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 1.0761671422261E-8

Ranking 16179/18225 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 0.14585116656279

Ranking 84/18665 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 -0.26157682321432

Ranking 16584/20870 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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