TGM7

Summary

TGM7 (transglutaminase 7, HGNC:30790) is a protein-coding gene on chromosome 15q15.2, encoding Protein-glutamine gamma-glutamyltransferase Z (Q96PF1). Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.

Transglutaminases (TGM; EC 2.3.2.13) are a family of structurally and functionally related enzymes that stabilize protein assemblies through the formation of gamma-glutamyl-epsilon lysine crosslinks. For additional background information on transglutaminases, see TGM1 (MIM 190195).

Source: NCBI Gene 116179 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_052955

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30790
Approved symbol	TGM7
Name	transglutaminase 7
Location	15q15.2
Locus type	gene with protein product
Status	Approved
Aliases	TGMZ
Ensembl gene	ENSG00000159495
Ensembl biotype	protein_coding
OMIM	606776
Entrez	116179

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000452443, ENST00000562372

RefSeq mRNA: 1 — MANE Select: NM_052955 NM_052955

CCDS: CCDS32213

Canonical transcript exons

ENST00000452443 — 13 exons

Exon	Start	End
ENSE00001045952	43293449	43293631
ENSE00001147370	43276862	43276995
ENSE00001147376	43279117	43279277
ENSE00001147380	43279625	43279951
ENSE00001147386	43281844	43282086
ENSE00001147390	43282517	43282620
ENSE00001147397	43284814	43284952
ENSE00001147401	43287280	43287457
ENSE00001147404	43287541	43287669
ENSE00001147405	43291979	43292097
ENSE00001147409	43292709	43292954
ENSE00001600449	43302241	43302255
ENSE00003465974	43276271	43276614

Expression profiles

Bgee: expression breadth broad, 66 present calls, max score 85.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0023 / max 3.2212, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149602	0.0023	1

Top tissues by expression

217 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	85.02	gold quality
oocyte	CL:0000023	84.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.51	gold quality
gingival epithelium	UBERON:0001949	75.17	silver quality
left testis	UBERON:0004533	70.95	gold quality
gingiva	UBERON:0001828	68.91	silver quality
right testis	UBERON:0004534	68.88	gold quality
testis	UBERON:0000473	67.88	gold quality
sperm	CL:0000019	65.31	gold quality
colonic epithelium	UBERON:0000397	63.38	gold quality
gastrocnemius	UBERON:0001388	58.25	gold quality
amniotic fluid	UBERON:0000173	56.45	gold quality
muscle of leg	UBERON:0001383	53.91	gold quality
tonsil	UBERON:0002372	50.25	gold quality
cerebellar vermis	UBERON:0004720	48.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	48.60	gold quality
mammalian vulva	UBERON:0000997	47.38	gold quality
thymus	UBERON:0002370	47.07	gold quality
vagina	UBERON:0000996	46.48	gold quality
bone marrow cell	CL:0002092	46.24	gold quality
esophagus mucosa	UBERON:0002469	45.04	gold quality
body of tongue	UBERON:0011876	44.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
prostate gland	UBERON:0002367	43.35	gold quality
superior surface of tongue	UBERON:0007371	43.31	gold quality
tongue	UBERON:0001723	42.94	gold quality
lower lobe of lung	UBERON:0008949	42.68	silver quality
quadriceps femoris	UBERON:0001377	42.59	gold quality
epithelium of nasopharynx	UBERON:0001951	42.29	gold quality
myocardium	UBERON:0002349	42.20	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1

miRNA regulators (miRDB)

6 targeting TGM7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-103B	95.51	66.85	441

Literature-anchored findings (GeneRIF, showing 1)

• Then, using the most efficient peptide, Z3S, we established an in vitro assay system to assess enzymatic activity of TG7. (PMID:23876241)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tgm8	ENSDARG00000097651
danio_rerio	tgm5l	ENSDARG00000098837
mus_musculus	Tgm7	ENSMUSG00000079103
rattus_norvegicus	Tgm7	ENSRNOG00000037203

Paralogs (8): TGM1 (ENSG00000092295), TGM5 (ENSG00000104055), F13A1 (ENSG00000124491), TGM3 (ENSG00000125780), TGM4 (ENSG00000163810), EPB42 (ENSG00000166947), TGM6 (ENSG00000166948), TGM2 (ENSG00000198959)

Protein

Protein identifiers

Protein-glutamine gamma-glutamyltransferase Z — Q96PF1 (reviewed: Q96PF1)

Alternative names: Transglutaminase Z, Transglutaminase-7

All UniProt accessions (1): Q96PF1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.

Tissue specificity. Widely expressed.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Similarity. Belongs to the transglutaminase superfamily. Transglutaminase family.

RefSeq proteins (1): NP_443187* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001102	Transglutaminase_N	Domain
IPR002931	Transglutaminase-like	Domain
IPR008958	Transglutaminase_C	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013808	Transglutaminase_AS	Active_site
IPR014756	Ig_E-set	Homologous_superfamily
IPR023608	Transglutaminase_animal	Family
IPR036238	Transglutaminase_C_sf	Homologous_superfamily
IPR036985	Transglutaminase-like_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050779	Transglutaminase	Family

Pfam: PF00868, PF00927, PF01841

Enzyme classification (BRENDA):

• EC 2.3.2.13 — protein-glutamine gamma-glutamyltransferase (BRENDA: 68 organisms, 476 substrates, 772 inhibitors, 122 Km, 49 kcat entries)

Substrate kinetics (BRENDA)

60 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PUTRESCINE	0.035–9.63	13
L-LYSINE	2.9–15.8	6
N-CBZ-GLN-GLY	12.83–59.5	5
HYDROXYLAMINE	1.37–61.9	4
NALPHA-BENZYLOXYCARBONYL-L-GLN-GLY	11.2–30	4
CASEIN	0.006–0.012	3
CBZ-GLN-GLY	0.0169–5.9	3
CBZ-GLN-GLY-OH	3.53–8.55	3
METHYLAMINE	0.024–0.061	3
MONODANSYLCADAVERINE	0.01–0.034	3
N-CARBOXYBENZOYL-L-GLUTAMINYL-GLYCINE	0.0547–69.4	3
PENTYLAMINE	0.0029–0.0203	3
Z-GLN-GLY	1.8–11.6	3
ACETYL-ALPHAS1-CASEIN	0.0029–0.0032	2
GTP	0.0044–0.01	2

Catalyzed reactions (Rhea), 1 shown:

• L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L-lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+) (RHEA:54816)

UniProt features (8 total): binding site 4, active site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PF1-F1	92.41	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 279; 338; 361

Ligand- & substrate-binding residues (4): 401; 403; 450; 455

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): GOBP_PEPTIDE_CROSS_LINKING, TGANTCA_AP1_C, RGAGGAARY_PU1_Q6, MODULE_95, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, HMGIY_Q6, GOMF_PROTEIN_GLUTAMINE_GAMMA_GLUTAMYLTRANSFERASE_ACTIVITY, MODULE_163, MIR505_5P, GSE8685_IL2_ACT_IL2_STARVED_VS_IL21_ACT_IL2_STARVED_CD4_TCELL_DN, NABA_ECM_REGULATORS, GSE17974_CTRL_VS_ACT_IL4_AND_ANTI_IL12_0.5H_CD4_TCELL_UP, GSE17974_CTRL_VS_ACT_IL4_AND_ANTI_IL12_4H_CD4_TCELL_UP, FOXM1_01

GO Biological Process (1): peptide cross-linking (GO:0018149)

GO Molecular Function (5): protein-glutamine gamma-glutamyltransferase activity (GO:0003810), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification process	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
cation binding	1
binding	1
catalytic activity	1
transferase activity	1

Protein interactions and networks

STRING

462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TGM7	PLEKHG5	O94827	507
TGM7	KLHL6	Q8WZ60	487
TGM7	KLHL7	Q8IXQ5	456
TGM7	ZMYM3	Q14202	453
TGM7	LHFPL5	Q8TAF8	415
TGM7	KRTAP19-7	Q3SYF9	370
TGM7	DMTN	Q08495	350
TGM7	GRAMD2A	Q8IUY3	338
TGM7	DCST1	Q5T197	324
TGM7	LRP1B	Q9NZR2	323
TGM7	SFTA3	P0C7M3	323
TGM7	VMO1	Q7Z5L0	320
TGM7	CD47	Q08722	318
TGM7	OR6X1	Q8NH79	311
TGM7	OR13J1	Q8NGT2	305

IntAct

65 interactions, top by confidence:

A	B	Type	Score
TGM7	PPCDC	psi-mi:“MI:0915”(physical association)	0.560
PPCDC	TGM7	psi-mi:“MI:0915”(physical association)	0.560
KCTD1	TGM7	psi-mi:“MI:0915”(physical association)	0.560
FRS3	TGM7	psi-mi:“MI:0915”(physical association)	0.560
TNXB	TGM7	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	TGM7	psi-mi:“MI:0915”(physical association)	0.560
SPATA18	TGM7	psi-mi:“MI:0915”(physical association)	0.560
	TGM7	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	TGM7	psi-mi:“MI:0915”(physical association)	0.560
QARS1	TGM7	psi-mi:“MI:0915”(physical association)	0.560
SDS	TGM7	psi-mi:“MI:0915”(physical association)	0.560
KRT39	TGM7	psi-mi:“MI:0915”(physical association)	0.560
GEM	TGM7	psi-mi:“MI:0915”(physical association)	0.560
TGM7	TSSK3	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	TGM7	psi-mi:“MI:0915”(physical association)	0.560
TGM7	UNKL	psi-mi:“MI:0915”(physical association)	0.560
LNX1	TGM7	psi-mi:“MI:0915”(physical association)	0.560
TGM7	LAMTOR3	psi-mi:“MI:0915”(physical association)	0.560
SAXO4	TGM7	psi-mi:“MI:0915”(physical association)	0.560
SPRY1	TGM7	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	TGM7	psi-mi:“MI:0915”(physical association)	0.560
TGM7	HGS	psi-mi:“MI:0914”(association)	0.350
TGM7	KCTD1	psi-mi:“MI:0915”(physical association)	0.000
FRS3	TGM7	psi-mi:“MI:0915”(physical association)	0.000
TNXB	TGM7	psi-mi:“MI:0915”(physical association)	0.000
TGM7	ARID5A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): TGM7 (Two-hybrid), TGM7 (Two-hybrid), TGM7 (Two-hybrid), TGM7 (Two-hybrid), TGM7 (Two-hybrid), TGM7 (Two-hybrid), TGM7 (Two-hybrid), TGM7 (Two-hybrid), TGM7 (Two-hybrid), PPP1R32 (Two-hybrid), TSSK3 (Two-hybrid), SPATA18 (Two-hybrid), SPRY1 (Two-hybrid), GEM (Two-hybrid), TNXB (Two-hybrid)

ESM2 similar proteins: A0A1W2PQ27, A0A1W2PQ64, A0A1W2PQC6, A0A1W2PQD8, A0A1W2PQJ5, A0A1W2PR75, A2AV36, A4QN59, A6QQV6, D4A1F2, F1RA39, G5E8F4, J9SQF3, O00142, O42868, O55239, O95050, O95932, O97972, P0CR76, P0CR77, P10938, P40261, P40936, P53538, Q01841, Q22453, Q32LP9, Q4R7D0, Q566Y1, Q5M9G7, Q5RFR7, Q5U4E8, Q5XG58, Q62160, Q6C195, Q6CQ61, Q6DE00, Q6FMU7, Q6PCI6

Diamond homologs: A6QP57, D4A5U3, O08619, O43548, O46510, O95932, P00488, P08587, P16452, P21980, P21981, P22735, P22758, P23606, P49221, P51176, P52181, P52183, Q01841, Q05187, Q08188, Q08189, Q8BH61, Q8BZH1, Q96PF1, Q99041, Q9D7I9, Q9GLK0, Q9JLF6, Q9WVJ6, P49222, P12260

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

123 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2142 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43276610:CAAGG:C	acceptor_gain	1.0000
15:43276860:A:AC	donor_gain	1.0000
15:43276860:ACT:A	donor_gain	1.0000
15:43276860:ACTC:A	donor_gain	1.0000
15:43276861:C:CA	donor_gain	1.0000
15:43276861:CT:C	donor_gain	1.0000
15:43276861:CTC:C	donor_gain	1.0000
15:43276861:CTCC:C	donor_gain	1.0000
15:43276861:CTCCT:C	donor_gain	1.0000
15:43276863:C:CA	donor_gain	1.0000
15:43276993:CAC:C	acceptor_gain	1.0000
15:43276993:CACCT:C	acceptor_loss	1.0000
15:43276994:ACCTG:A	acceptor_loss	1.0000
15:43276997:T:A	acceptor_loss	1.0000
15:43276998:G:C	acceptor_gain	1.0000
15:43279173:T:TA	donor_gain	1.0000
15:43279174:C:A	donor_gain	1.0000
15:43279623:AC:A	donor_gain	1.0000
15:43279624:CC:C	donor_gain	1.0000
15:43281853:A:AC	donor_gain	1.0000
15:43281854:C:CC	donor_gain	1.0000
15:43282511:A:AC	donor_gain	1.0000
15:43282512:C:CC	donor_gain	1.0000
15:43282513:TCA:T	donor_loss	1.0000
15:43282515:A:AC	donor_gain	1.0000
15:43282516:C:A	donor_loss	1.0000
15:43282516:C:CC	donor_gain	1.0000
15:43282516:CCA:C	donor_gain	1.0000
15:43282617:GTTC:G	acceptor_gain	1.0000
15:43282618:TTC:T	acceptor_gain	1.0000

AlphaMissense

4669 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43287368:A:C	S259R	0.993
15:43287368:A:T	S259R	0.993
15:43287370:T:G	S259R	0.993
15:43293533:G:T	R37S	0.987
15:43284909:G:C	F303L	0.985
15:43284909:G:T	F303L	0.985
15:43284911:A:G	F303L	0.985
15:43282596:G:C	C343W	0.983
15:43282614:G:C	F337L	0.983
15:43282614:G:T	F337L	0.983
15:43282616:A:G	F337L	0.983
15:43282556:A:G	W357R	0.982
15:43282556:A:T	W357R	0.982
15:43292095:C:G	D148H	0.982
15:43284925:C:G	R298P	0.981
15:43282607:A:G	W340R	0.980
15:43282607:A:T	W340R	0.980
15:43282042:C:A	G385W	0.978
15:43287547:A:C	S227R	0.978
15:43287547:A:T	S227R	0.978
15:43287549:T:G	S227R	0.978
15:43282598:A:G	C343R	0.977
15:43284919:A:T	V300D	0.977
15:43282071:C:T	G375D	0.976
15:43282576:A:G	L350P	0.976
15:43282585:C:G	R347P	0.976
15:43293532:C:G	R37P	0.975
15:43287299:G:C	F282L	0.974
15:43287299:G:T	F282L	0.974
15:43287301:A:G	F282L	0.974

dbSNP variants (sampled 300 via entrez): RS1000048500 (15:43291517 T>C), RS1000199967 (15:43303853 A>G), RS1000223377 (15:43297683 G>A), RS1000273599 (15:43304090 G>A,T), RS1000526789 (15:43298944 A>C,G,T), RS1000587307 (15:43302338 C>G,T), RS1000603027 (15:43292721 G>T), RS1000949259 (15:43292903 C>A,G,T), RS1001057702 (15:43302623 G>A,T), RS1001201600 (15:43296299 C>T), RS1001266924 (15:43290281 A>G), RS1001426293 (15:43302847 T>C), RS1001481252 (15:43277674 A>G,T), RS1001638409 (15:43277772 T>C), RS1001649116 (15:43280007 G>A,T)

Disease associations

OMIM: gene MIM:606776 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Coal	increases abundance, increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.