Human Gene Module / Chromosome 19 / LMTK3

LMTK3lemur tyrosine kinase 3

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
8 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
19q13.33
Associated Disorders
-
Relevance to Autism

LMTK3 was identified as an ASD candidate gene based on having a p-value < 0.001 following DeNovoWEST analysis of de novo variants in 16,877 ASD trios from the Simons Simplex Collection, the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort in Zhou et al., 2022; among the de novo variants observed in ASD cases in this analysis were two de novo loss-of-function variants and two damaging de novo missense variants (defined as having a REVEL score > 0.5). Inoue et al., 2014 demonstrated that Lmtk3-knockout mice exhibited behavioral abnormalities (locomotor hyperactivity, reduced anxiety, and decreased depression-like behavior) and impaired endocytotic trafficking of NMDA receptors, while Montrose et al., 2019 demonstrated that Lmtk3-knockout mice displayed behavioral abnormalities (including hypersociability, PPI defects, and impaired cognitive function), severely impaired long-term potentiation induction, and abnormal GluA1 trafficking after AMPA stimulation.

Molecular Function

Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in Golgi membrane; axon; and dendrite. Predicted to be integral component of membrane. Involved in endocytic trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LMTK3 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Inoue T et al. (2014) No -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
4 Support - Montrose K et al. (2019) No -
5 Primary - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.848T>C p.Leu283Pro missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1265G>A p.Arg422Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3560C>G p.Pro1187Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.854A>G p.His285Arg missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1519G>C p.Glu507Gln missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.915_916insTGACCTG p.Asp306Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1737del p.Glu579AspfsTer58 frameshift_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.2637_2638del p.Lys879AsnfsTer689 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
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.

10/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.46218603832388

Ranking 9331/25841 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
Sanders TADA Score

Score 0.52024337791592

Ranking 493/18665 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 -0.10730323034524

Ranking 12621/20870 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
Submit New Gene

Report an Error