THG1L

tRNA-histidine guanylyltransferase 1 like

Basic information

Region (hg38): 5:157731420-157741449

Links

ENSG00000113272 ∙ NCBI:54974 ∙ OMIM:618802 ∙ HGNC:26053 ∙ Uniprot:Q9NWX6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia, autosomal recessive 28 (Moderate), mode of inheritance: AD
• spinocerebellar ataxia, autosomal recessive 28 (Strong), mode of inheritance: AR
• spinocerebellar ataxia, autosomal recessive 28 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 28	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic; Ophthalmologic	27307223; 30214071; 31168944

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THG1L gene.

• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THG1L gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense		2	23		1	26
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	1	2	23	3	2

Highest pathogenic variant AF is 0.00000657

Variants in THG1L

This is a list of pathogenic ClinVar variants found in the THG1L region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-157731431-C-A		THG1L-related disorder	Benign (Nov 20, 2019)
5-157731450-G-A			Uncertain significance (Aug 20, 2022)
5-157731486-A-G		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
5-157731570-G-A		Inborn genetic diseases	Uncertain significance (Oct 11, 2021)
5-157731576-A-T		not specified	Uncertain significance (Mar 19, 2020)
5-157731577-C-A		Spinocerebellar ataxia, autosomal recessive 28 • Inborn genetic diseases	Uncertain significance (Nov 16, 2021)
5-157731588-C-G		Inborn genetic diseases	Uncertain significance (Nov 20, 2024)
5-157731604-T-C		Spinocerebellar ataxia, autosomal recessive 28	Likely pathogenic (Mar 30, 2023)
5-157731606-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
5-157731609-C-G		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
5-157731622-A-C		Neurodevelopmental disorder	Likely pathogenic (May 04, 2021)
5-157732885-A-G		Inborn genetic diseases	Uncertain significance (Sep 10, 2024)
5-157732906-G-A		Inborn genetic diseases	Uncertain significance (Jul 20, 2022)
5-157732936-C-T			Uncertain significance (Jul 24, 2019)
5-157732961-G-A			Likely benign (Jun 01, 2024)
5-157732963-A-T		Inborn genetic diseases	Uncertain significance (Feb 24, 2023)
5-157732973-C-T			Likely benign (Jun 01, 2022)
5-157732978-A-G		Inborn genetic diseases	Uncertain significance (May 20, 2021)
5-157732989-G-A			Uncertain significance (Mar 02, 2017)
5-157734596-C-T		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
5-157734631-C-T		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
5-157734701-G-A		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
5-157734724-C-T		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
5-157734728-G-C			Uncertain significance (Nov 12, 2023)
5-157734733-C-T			Uncertain significance (Nov 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THG1L	protein_coding	protein_coding	ENST00000231198	6	10252

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000528	0.888	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0266	169	170	0.994	0.00000881	1988
Missense in Polyphen		59	65.002	0.90766		715
Synonymous	-0.590	69	63.0	1.09	0.00000349	535
Loss of Function	1.48	9	15.2	0.591	7.29e-7	173

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000250	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000190	0.000167
Middle Eastern	0.00	0.00
South Asian	0.000136	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage. This step is essential for proper recognition of the tRNA and for the fidelity of protein synthesis. {ECO:0000269|PubMed:21059936}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.727
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.0311
• hipred: N
• hipred_score: 0.204
• ghis: 0.611

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Thg1l

Gene ontology

• Biological process: tRNA modification;tRNA processing;protein homotetramerization;tRNA 5'-end processing
• Cellular component: mitochondrion;cytosol
• Molecular function: tRNA binding;magnesium ion binding;protein binding;ATP binding;GTP binding;tRNA guanylyltransferase activity;nucleotidyltransferase activity;identical protein binding