TMLHE

trimethyllysine hydroxylase, epsilon

Basic information

Region (hg38): X:155489011-155719098

Links

ENSG00000185973 ∙ NCBI:55217 ∙ OMIM:300777 ∙ HGNC:18308 ∙ Uniprot:Q9NVH6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epsilon-trimethyllysine hydroxylase deficiency (Limited), mode of inheritance: Unknown
• autism spectrum disorder (Disputed Evidence), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epsilon-trimethyllysine hydroxylase deficiency	AD	Biochemical	The condition may be associated with autism, and carnitine supplementation has been reported as beneficial related to developmental milestones	Biochemical; Neurologic	21865298; 22566635; 25943046

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMLHE gene.

• not_specified (40 variants)
• not_provided (20 variants)
• Epsilon-trimethyllysine_hydroxylase_deficiency (15 variants)
• TMLHE-related_disorder (6 variants)
• Congenital_cerebellar_hypoplasia (1 variants)
• Corpus_callosum,_agenesis_of (1 variants)
• Cerebellar_vermis_hypoplasia (1 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMLHE gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018196.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	6	1	8
missense		1	44	5		50
nonsense			5			5
start loss						0
frameshift	1					1
splice donor/acceptor (+/-2bp)		2	3			5
Total	1	3	53	11	1

Highest pathogenic variant AF is 0.000010760209

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMLHE	protein_coding	protein_coding	ENST00000334398	7	179830

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000796	0.777	125709	12	16	125737	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.637	112	133	0.844	0.00000987	2753
Missense in Polyphen		37	47.984	0.77109		933
Synonymous	-0.348	54	50.8	1.06	0.00000380	786
Loss of Function	1.13	8	12.3	0.652	8.29e-7	250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000431	0.000415
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.00	0.00
Finnish	0.0000627	0.0000462
European (Non-Finnish)	0.0000998	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.000449	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML) (PubMed:11431483, PubMed:23092983). {ECO:0000269|PubMed:11431483, ECO:0000269|PubMed:23092983}.
• Pathway: Lysine degradation - Homo sapiens (human);Carnitine Synthesis;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Metabolism;Lysine degradation;Lysine metabolism;Carnitine synthesis;L-carnitine biosynthesis (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.228
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.194
• hipred: N
• hipred_score: 0.350
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.879

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tmlhe

Gene ontology

• Biological process: carnitine biosynthetic process;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: iron ion binding;protein binding;oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen;trimethyllysine dioxygenase activity