TGM4

protein-coding

transglutaminase 4, the group of Transglutaminases

Gene summary

Predicted to enable protein-glutamine gamma-glutamyltransferase activity. Predicted to be involved in peptide cross-linking. Predicted to act upstream of or within mating plug formation. Located in Golgi apparatus and extracellular matrix. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_003241.4

Inheritance

—

ClinVar variants

P:1U:96B:9

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr3:44,874,608-44,914,990

External References & Databases

Ensembl (ENSG00000163810)

Transcript & Mutation Effects

hg38 • Region Span ~40.4 kb

Loading mutation effect viewer...

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 TGM4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Essential tremorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003241.4. 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				3 clinvar	3 clinvar	6
missense			95 clinvar	2 clinvar	1 clinvar	98
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	96	5	4	106

Highest pathogenic variant AF is 0.007854279

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003241.4	RefSeq	NP_003232.2	14	MANE Select
ENST00000296125.9	Ensembl	ENSP00000296125.4	14	MANE Select
ENST00000422219.5	Ensembl	ENSP00000403711.1	3	Standard
ENST00000705784.1	Ensembl	ENSP00000516167.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

peptide cross-linking

Molecular Function

protein-glutamine gamma-glutamyltransferase activity
metal ion binding

Cellular Component

cytoplasm
Golgi apparatus
collagen-containing extracellular matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296125
Coding exons: 14
Length: 40383
Individuals with no LoFs: 123212
Homozygous LoFs: 24
Heterozygous LoFs: 2511
Defined: 125747
p: 0.0101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0135	386	387	0.998	0.0000212	4508
Missense (PolyPhen)		134	125.1	1.0711		1427
Synonymous	-0.781	176	163	1.08	0.0000105	1302
Loss of Function	0.564	32	35.6	0.898	0.00000188	379

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0016	0.0016	notable
Latino/Admixed American	0.0086	0.0086	notable
Ashkenazi Jewish	0.023	0.023	notable
East Asian	0.00098	0.00098	rare
Finnish	0.012	0.012	notable
European (Non-Finnish)	0.0099	0.0099	notable
South Asian	0.017	0.017	notable
Other	0.012	0.012	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Associated with the mammalian reproductive process. Catalyzes the cross-linking of proteins and the conjugation of polyamines to specific proteins in the seminal tract.;

Recessive Scores

pRec: 0.472

Intolerance Scores

LoFtool: 0.284
RVIS EVS: 0.9
RVIS percentile EVS: 89.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00602

Gene Damage Prediction

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