TGS1

protein-coding

trimethylguanosine synthase 1, the group of 7BS DNA/RNA methyltransferases

Gene summary

Enables RNA cap trimethylguanosine synthase activity. Involved in 7-methylguanosine cap hypermethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

NCOA6IP

MANE transcript

NM_024831.8

Inheritance

—

ClinVar variants

U:127B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr8:55,773,446-55,826,445

External References & Databases

Ensembl (ENSG00000137574)

Transcript & Mutation Effects

hg38 • Region Span ~53.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TGS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 126

not providedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024831.8. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	2 clinvar	5
missense			123 clinvar	11 clinvar	7 clinvar	141
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	127	12	9	148

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024831.8	RefSeq	NP_079107.6	13	MANE Select
ENST00000260129.6	Ensembl	ENSP00000260129.5	13	MANE Select
NM_001317902.2	RefSeq	NP_001304831.1	10	Standard
NM_001363184.2	RefSeq	NP_001350113.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
Metabolism of lipids
snRNP Assembly
Metabolism of RNA

Biological Process

spliceosomal snRNP assembly
7-methylguanosine RNA capping
regulation of lipid metabolic process
ribonucleoprotein complex biogenesis
7-methylguanosine cap hypermethylation

Molecular Function

protein binding
RNA methyltransferase activity
RNA trimethylguanosine synthase activity

Cellular Component

extracellular space
nucleus
nucleoplasm
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260129
Coding exons: 13
Length: 52307
Individuals with no LoFs: 125667
Homozygous LoFs: 0
Heterozygous LoFs: 81
Defined: 125748
p: 0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.16	503	435	1.16	0.0000207	5682
Missense (PolyPhen)		147	136.76	1.0749		1748
Synonymous	-0.285	158	154	1.03	0.00000780	1496
Loss of Function	2.01	25	38.4	0.650	0.00000169	531

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00070	0.00069	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00050	0.00049	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation. {ECO:0000269|PubMed:11517327, ECO:0000269|PubMed:11912212, ECO:0000269|PubMed:16687569, ECO:0000269|PubMed:18775984}.;

Recessive Scores

pRec: 0.154

Intolerance Scores

LoFtool: 0.885
RVIS EVS: 2.61
RVIS percentile EVS: 98.77

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.518

Gene Damage Prediction

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