Aliases: BBOX2, FLJ10727, TMLD, TMLH, XAP130
Chromosome No: X
Chromosome Band: Xq28
Genetic Category: Rare Single Gene variant-Genetic association/rare single gene variant-Functional
ASD Reports: 10
Recent Reports: 2
Annotated variants: 14
Associated CNVs: 11
Evidence score: 3
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Relevance to Autism
A rare mutation in the TMLHE gene has been identified with autism (Celestino-Soper et al., 2011). In a follow-up study, TMLHE deficiency caused by deletion of exon 2 was shown to be 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 compared to 24 in 8787; P = 0.023) (Celestino-Soper et al., 2012). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (meta-analysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism.
Molecular Function
This gene encodes the protein trimethyllysine dioxygenase which is the first enzyme in the carnitine biosynthesis pathway. Carnitine plays an essential role in the transport of activated fatty acids across the inner mitochondrial membrane. The encoded protein converts trimethyllysine into hydroxytrimethyllysine.
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