THUMPD2

protein-coding

THUMP domain containing 2, the group of 7BS DNA/RNA methyltransferases

Gene summary

Enables U6 snRNA (guanine-N(2))-methyltransferase activity. Involved in regulation of alternative mRNA splicing, via spliceosome. Part of tRNA methyltransferase complex. Is active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C2orf8

MANE transcript

NM_025264.5

Inheritance

—

ClinVar variants

U:98B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr2:39,736,060-39,779,267

External References & Databases

Ensembl (ENSG00000138050)

Transcript & Mutation Effects

hg38 • Region Span ~43.2 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 THUMPD2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 95

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025264.5. 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						0
missense			95 clinvar	3 clinvar		98
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	98	3	0	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025264.5	RefSeq	NP_079540.2	10	MANE Select
ENST00000505747.6	Ensembl	ENSP00000423933.1	10	MANE Select
NM_001321468.1	RefSeq	NP_001308397.1	10	Standard
NM_001321469.1	RefSeq	NP_001308398.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

tRNA methylation

Molecular Function

RNA binding
tRNA (guanine) methyltransferase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000505747
Coding exons: 10
Length: 43208
Individuals with no LoFs: 125666
Homozygous LoFs: 0
Heterozygous LoFs: 77
Defined: 125743
p: 0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.617	264	237	1.11	0.0000112	3293
Missense (PolyPhen)		86	79.439	1.0826		1080
Synonymous	-0.399	90	85.3	1.05	0.00000442	926
Loss of Function	0.915	16	20.5	0.782	9.50e-7	282

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00053	0.00052	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.0017	0.0017	notable
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00015	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0980

Intolerance Scores

LoFtool: 0.314
RVIS EVS: -0.58
RVIS percentile EVS: 18.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.372

Gene Damage Prediction

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