TRIM72

Summary

TRIM72 (tripartite motif containing 72, HGNC:32671) is a protein-coding gene on chromosome 16p11.2, encoding Tripartite motif-containing protein 72 (Q6ZMU5). Muscle-specific E3 ubiquitin-protein ligase that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites.

Enables identical protein binding activity. Predicted to be involved in several processes, including plasma membrane repair; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein homooligomerization. Predicted to act upstream of or within negative regulation of insulin receptor signaling pathway; negative regulation of insulin-like growth factor receptor signaling pathway; and negative regulation of myotube differentiation. Predicted to be located in cytoplasmic vesicle membrane. Predicted to be active in cytoplasm and sarcolemma.

Source: NCBI Gene 493829 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001008274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32671
Approved symbol	TRIM72
Name	tripartite motif containing 72
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	MG53
Ensembl gene	ENSG00000177238
Ensembl biotype	protein_coding
OMIM	613288
Entrez	493829

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000322122

RefSeq mRNA: 1 — MANE Select: NM_001008274 NM_001008274

CCDS: CCDS32437

Canonical transcript exons

ENST00000322122 — 7 exons

Exon	Start	End
ENSE00001243182	31220896	31220918
ENSE00001243189	31219289	31219519
ENSE00001292877	31224181	31231537
ENSE00001306390	31219095	31219190
ENSE00001322888	31222827	31222945
ENSE00001326837	31214732	31215128
ENSE00001402196	31214119	31214297

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 96.73.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.3043 / max 129.8083, expressed in 134 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153794	0.5849	90
153793	0.4591	92
153792	0.2283	75
153791	0.0320	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.73	gold quality
gastrocnemius	UBERON:0001388	96.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.78	gold quality
quadriceps femoris	UBERON:0001377	94.70	gold quality
vastus lateralis	UBERON:0001379	94.70	gold quality
muscle of leg	UBERON:0001383	94.62	gold quality
skeletal muscle tissue	UBERON:0001134	93.56	gold quality
biceps brachii	UBERON:0001507	93.52	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.41	gold quality
muscle tissue	UBERON:0002385	88.12	gold quality
buccal mucosa cell	CL:0002336	85.05	gold quality
body of tongue	UBERON:0011876	78.97	gold quality
cerebellar cortex	UBERON:0002129	75.87	gold quality
cerebellar hemisphere	UBERON:0002245	75.78	gold quality
cerebellum	UBERON:0002037	75.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.05	gold quality
tongue	UBERON:0001723	73.70	gold quality
deltoid	UBERON:0001476	73.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.38	gold quality
superior surface of tongue	UBERON:0007371	66.09	gold quality
cerebellar vermis	UBERON:0004720	65.65	gold quality
oocyte	CL:0000023	65.43	gold quality
trabecular bone tissue	UBERON:0002483	63.29	silver quality
pharyngeal mucosa	UBERON:0000355	63.09	gold quality
nasal cavity epithelium	UBERON:0005384	61.16	gold quality
oral cavity	UBERON:0000167	60.47	silver quality
apex of heart	UBERON:0002098	60.13	gold quality
secondary oocyte	CL:0000655	60.01	gold quality
jejunum	UBERON:0002115	59.52	gold quality
myocardium	UBERON:0002349	57.92	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	121.92
E-GEOD-76312	yes	43.70
E-MTAB-3929	yes	36.37
E-ANND-3	yes	4.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A, MYOD1, MYOG

miRNA regulators (miRDB)

17 targeting TRIM72, 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-150-5P	99.99	66.69	1976
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 28)

• Crystal structure of PRY-SPRY domain of human TRIM72. (PMID:19967786)
• membrane-delimited interaction between MG53 and PTRF contributes to initiation of cell membrane repair (PMID:21343302)
• MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch (PMID:21412170)
• data reveal NM-IIA as a key cytoskeleton motor protein that facilitates vesicle trafficking during MG53-mediated cell membrane repair (PMID:22253476)
• MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types. (PMID:23699904)
• TRIM proteins trim the balance of homoeostasis by modulating various biological pathways through protein-protein interactions. (PMID:23969027)
• MG53 induces FAK ubiquitination with the aid of UBE2H during skeletal myogenesis. (PMID:24344130)
• Zn(2+) interacts with MG53 in protection against injury to the cell membrane (PMID:25869134)
• MG53 is a facilitator of rapid injury repair, a mediator of cell migration, and a modulator of myofibroblast differentiation during wound healing (PMID:26306047)
• MG53 is an effective biomarker of myocardial injury and dysfunction in murine hearts. However, MG53 is not expressed in human heart and therefore does not hold utility as a clinical biomarker of myocardial injury (PMID:26790476)
• CRIg is a novel interacting partner of TRIM72 in the lung. (PMID:29268030)
• serum TRIM72 may be a potential biomarker for the diagnosis and the prognosis of colon cancer. (PMID:29806630)
• TRIM72 Immunohistochemical Expression Can Predict Relapse in Colorectal Carcinoma. (PMID:30852740)
• MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury. (PMID:31779687)
• TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis. (PMID:32471489)
• MG53 suppresses interferon-beta and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling. (PMID:32681036)
• MG53/CAV1 regulates transforming growth factor-beta1 signaling-induced atrial fibrosis in atrial fibrillation. (PMID:33000676)
• Targeting TRIM Proteins: A Quest towards Drugging an Emerging Protein Class. (PMID:33482040)
• MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle. (PMID:33566837)
• Functional and Adaptive Significance of Promoter Mutations That Affect Divergent Myocardial Expressions of TRIM72 in Primates. (PMID:33744959)
• MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung cancer. (PMID:34521423)
• Ubiquitination and degradation of MGMT by TRIM72 increases the sensitivity of uveal melanoma cells to Dacarbazine treatment. (PMID:34958003)
• TRIM72 exerts antitumor effects in breast cancer and modulates lactate production and MCT4 promoter activity by interacting with PPP3CA. (PMID:35324524)
• MG53 represses high glucose-induced inflammation and angiogenesis in human retinal endothelial cells by repressing the EGR1/STAT3 axis. (PMID:35438597)
• Cryo-EM structure of human MG53 homodimer. (PMID:36053137)
• Tripartite motif 72 inhibits apoptosis and mitochondrial dysfunction in neural stem cells induced by anesthetic sevoflurane by activating PI3K/AKT pathway. (PMID:36814155)
• MG53 ameliorates nerve injury induced neuropathic pain through the regulation of Nrf2/HO-1 signaling in rats. (PMID:37169128)
• Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane. (PMID:39267782)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim72	ENSMUSG00000042828
rattus_norvegicus	Trim72	ENSRNOG00000022099

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890)

Protein

Protein identifiers

Tripartite motif-containing protein 72 — Q6ZMU5 (reviewed: Q6ZMU5)

Alternative names: Mitsugumin-53

All UniProt accessions (1): Q6ZMU5

UniProt curated annotations — full annotation on UniProt →

Function. Muscle-specific E3 ubiquitin-protein ligase that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. Its ubiquitination activity is mediated by E2 ubiquitin-conjugating enzymes UBE2D1, UBE2D2 and UBE2D3. Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site. This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation. Probably acts upstream of the Ca(2+)-dependent membrane resealing process. Required for transport of DYSF to sites of cell injury during repair patch formation. Regulates membrane budding and exocytosis. May be involved in the regulation of the mobility of KCNB1-containing endocytic vesicles.

Subunit / interactions. Homodimer. Homooligomer; disulfide-linked. Oligomerizes on the phospholipid membrane. Interacts with DYSF and CAV3.

Subcellular location. Cell membrane. Sarcolemma. Cytoplasmic vesicle membrane.

Post-translational modifications. Disulfide bond formation at Cys-242 occurs in case of membrane damage that cause the entry of the oxidized milieu of the extracellular space, resulting in homooligomerization. S-nitrosylation at Cys-144 stabilizes TRIM72 and protects against oxidation-induced protein degradation and cell death.

Activity regulation. Specifically binds phosphatidylserine. The binding to phospholipids enhances ubiquitination activity.

Domain organisation. The RING domain is flexible in both the dimer and oligomer. Binding to the negatively charged phosphatidylserine lipids is mediated by the positively charged PRYSPRY domains and is inhibited by Ca(2+).

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMU5-1	1	yes
Q6ZMU5-2	2

RefSeq proteins (1): NP_001008275* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13765, PF15227

UniProt features (85 total): mutagenesis site 26, strand 20, binding site 16, turn 6, helix 6, zinc finger region 2, modified residue 2, sequence conflict 2, chain 1, domain 1, disulfide bond 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3KB5	X-RAY DIFFRACTION	1.5
7XT2	X-RAY DIFFRACTION	3
7Y4S	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMU5-F1	91.06	0.74

Functional residue map

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

Ligand- & substrate-binding residues (16): 37; 53; 56; 86; 89; 97; 100; 105; 108; 114; 117; 14 …

Post-translational modifications (2): 144, 255

Disulfide bonds (1): 242

Mutagenesis-validated functional residues (26):

Position	Phenotype
95	disrupts membrane translocation upon peroxide and saponin treatment.
144	no decrease in level upon treatment with hydrogen peroxide.
169	reduced cell viability upon peroxide and saponin treatment. reduced affinity for phospho-l-serine; fails to translocate
169	reduced cell viability upon peroxide and saponin treatment.
176	monomeric; fails to translocate to membrane; reduced cell viability upon peroxide and saponin treatment; when associated
179	monomeric; fails to translocate to membrane; reduced cell viability upon peroxide and saponin treatment; when associated
179	disrupts membrane translocation. reduced cell viability upon peroxide and saponin treatment.
180	reduced cell viability upon peroxide and saponin treatment. reduced affinity for phospho-l-serine; fails to translocate
180	reduced cell viability upon peroxide and saponin treatment.
183	monomeric; fails to translocate to membrane; reduced cell viability upon peroxide and saponin treatment; when associated
186	monomeric; fails to translocate to membrane; reduced cell viability upon peroxide and saponin treatment; when associated
190	monomeric; fails to translocate to membrane; reduced cell viability upon peroxide and saponin treatment; when associated
198	reduced cell viability upon peroxide and saponin treatment. reduced affinity for phospho-l-serine; fails to translocate
198	reduced cell viability upon peroxide and saponin treatment.
220	reduced cell viability upon peroxide and saponin treatment.
220	fails to translocate to membrane and reduced cell viability upon peroxide and saponin treatment.
242	disrupts oligomerization and membrane translocation upon peroxide and saponin treatment.
272–281	abolishes binding to myoblast cell membrane.
272	disrupts membrane translocation. reduced cell viability upon peroxide and saponin treatment.
277	disrupts membrane translocation. reduced cell viability upon peroxide and saponin treatment.
279	disrupts membrane translocation. reduced cell viability upon peroxide and saponin treatment.
279	restores membrane translocation and cell viability upon peroxide and saponin treatment; when associated with k-433.
368–371	abolishes binding to myoblast cell membrane.
433	disrupts membrane translocation. reduced cell viability upon peroxide and saponin treatment.
433	restores membrane translocation and cell viability upon peroxide and saponin treatment; when associated with d-279.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-445355	Smooth Muscle Contraction

MSigDB gene sets: 111 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_WOUND_HEALING, GOBP_EXOCYTOSIS

GO Biological Process (10): plasma membrane repair (GO:0001778), muscle system process (GO:0003012), exocytosis (GO:0006887), muscle organ development (GO:0007517), negative regulation of myotube differentiation (GO:0010832), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of insulin-like growth factor receptor signaling pathway (GO:0043569), innate immune response (GO:0045087), negative regulation of insulin receptor signaling pathway (GO:0046627), protein homooligomerization (GO:0051260)

GO Molecular Function (9): phosphatidylserine binding (GO:0001786), zinc ion binding (GO:0008270), mitogen-activated protein kinase kinase kinase binding (GO:0031435), ubiquitin conjugating enzyme binding (GO:0031624), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): cytoplasm (GO:0005737), cytoplasmic vesicle membrane (GO:0030659), sarcolemma (GO:0042383), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of signal transduction	2
cellular anatomical structure	2
plasma membrane organization	1
wound healing	1
system process	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
animal organ development	1
muscle structure development	1
regulation of myotube differentiation	1
myotube differentiation	1
negative regulation of striated muscle cell differentiation	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
regulation of insulin-like growth factor receptor signaling pathway	1
insulin-like growth factor receptor signaling pathway	1
immune response	1
defense response to symbiont	1
insulin receptor signaling pathway	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
protein complex oligomerization	1
phospholipid binding	1
anion binding	1
modified amino acid binding	1
transition metal ion binding	1
protein kinase binding	1
ubiquitin-like protein conjugating enzyme binding	1
protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
vesicle membrane	1
cytoplasmic vesicle	1
plasma membrane	1
membrane	1

Protein interactions and networks

STRING

915 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM72	CAV3	P56539	955
TRIM72	DYSF	O75923	949
TRIM72	BBOX1	O75936	866
TRIM72	CAVIN1	Q6NZI2	780
TRIM72	TRAT1	Q6PIZ9	714
TRIM72	ANXA1	P04083	703
TRIM72	PRY	O14603	673
TRIM72	AHNAK	Q09666	668
TRIM72	UBE2H	P37286	634
TRIM72	CAPN3	P20807	608
TRIM72	MYOF	Q9NZM1	607
TRIM72	PARVB	Q9HBI1	603
TRIM72	ADPRH	P54922	492
TRIM72	IRS1	P35568	478
TRIM72	SYPL2	Q5VXT5	467

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
TRIM72	TCF12	psi-mi:“MI:0915”(physical association)	0.560
TCF12	TRIM72	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	MZT1	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	PPP3CA	psi-mi:“MI:0915”(physical association)	0.560
MED21	TRIM72	psi-mi:“MI:0915”(physical association)	0.560
NMI	TRIM72	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	C1orf216	psi-mi:“MI:0915”(physical association)	0.560
MZT1	TRIM72	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	ZNF655	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	ABI2	psi-mi:“MI:0915”(physical association)	0.560
PPP3CA	TRIM72	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	TRIM72	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	MED21	psi-mi:“MI:0915”(physical association)	0.560
TRIM72	UBE2I	psi-mi:“MI:0915”(physical association)	0.370
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CASP9	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
TRIM72	CCDC22	psi-mi:“MI:0914”(association)	0.350
MRPS23	MYH7B	psi-mi:“MI:0914”(association)	0.350
TRIM72	NMI	psi-mi:“MI:0915”(physical association)	0.000
TRIM72	TCF12	psi-mi:“MI:0915”(physical association)	0.000
C1orf216	TRIM72	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (90): TRIM72 (Two-hybrid), TRIM72 (Biochemical Activity), TRIM72 (Affinity Capture-Western), IRS1 (Affinity Capture-Western), TRIM72 (PCA), TRIM72 (Co-localization), CAV3 (Affinity Capture-Western), PTK2 (Affinity Capture-Western), TRIM72 (Affinity Capture-Western), TRIM72 (Affinity Capture-Western), UBE2H (Affinity Capture-Western), TRIM72 (Affinity Capture-Western), TRIM72 (PCA), TRIM72 (Affinity Capture-Western), IRS1 (PCA)

ESM2 similar proteins: A0JPQ4, E1BD59, O15197, P0C0K6, P62603, Q14142, Q1XH17, Q1XH18, Q3UWZ0, Q5BK82, Q5JZY3, Q5M929, Q5NCC3, Q5RBG2, Q5RKG6, Q5TM55, Q5W0U4, Q640S6, Q6P6S3, Q6PGR9, Q6PJ69, Q6ZMU5, Q7TPM3, Q7YR32, Q80VI1, Q80X56, Q80YW5, Q810I1, Q810I2, Q865W2, Q86UV6, Q86UV7, Q86XT4, Q8BFW4, Q8BVW3, Q8BYG9, Q8C006, Q8C0E3, Q8IUD6, Q8K243

Diamond homologs: A0JPQ4, A6QQX5, D3YY23, D3Z8N2, F6ZQ54, F8S122, O00478, O00481, O60858, O75677, P18892, P82885, P83234, Q13410, Q14258, Q17RB8, Q1XH17, Q1XH18, Q27J48, Q2XXL4, Q32L60, Q503I2, Q5EBN2, Q5M7V1, Q5R846, Q5R996, Q5TA31, Q5ZMD4, Q61510, Q62556, Q640S6, Q6PGR9, Q6QA27, Q6UX41, Q6UXG8, Q6ZMU5, Q7SZN2, Q7T308, Q7TST0, Q810I1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM72	ubiquitination
TRIM72	“down-regulates quantity by destabilization”	IRS1	ubiquitination
TRIM72	“down-regulates quantity by destabilization”	PTK2	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1200 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31214293:GACCT:G	donor_gain	1.0000
16:31214298:G:GG	donor_gain	1.0000
16:31216742:CCAG:C	donor_gain	1.0000
16:31219093:A:AG	acceptor_gain	1.0000
16:31219094:G:GG	acceptor_gain	1.0000
16:31219186:TGGAG:T	donor_loss	1.0000
16:31219187:GGAGG:G	donor_loss	1.0000
16:31219188:GAGG:G	donor_loss	1.0000
16:31219189:AG:A	donor_loss	1.0000
16:31219190:GGTGA:G	donor_loss	1.0000
16:31219191:G:C	donor_loss	1.0000
16:31219192:T:G	donor_loss	1.0000
16:31219517:ATGG:A	donor_loss	1.0000
16:31219520:G:GG	donor_gain	1.0000
16:31222819:A:AG	acceptor_gain	1.0000
16:31222822:CCCA:C	acceptor_loss	1.0000
16:31222823:CCA:C	acceptor_loss	1.0000
16:31222824:CA:C	acceptor_loss	1.0000
16:31222825:A:AG	acceptor_gain	1.0000
16:31222825:AGGCT:A	acceptor_loss	1.0000
16:31222826:G:GG	acceptor_gain	1.0000
16:31222826:GGCT:G	acceptor_gain	1.0000
16:31222920:G:GT	donor_gain	1.0000
16:31224179:A:AG	acceptor_gain	1.0000
16:31224180:G:GG	acceptor_gain	1.0000
16:31224750:GCC:G	donor_gain	1.0000
16:31214294:ACCTG:A	donor_loss	0.9900
16:31214295:CCT:C	donor_gain	0.9900
16:31214296:CTGTG:C	donor_loss	0.9900
16:31214297:TG:T	donor_loss	0.9900

AlphaMissense

3061 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31215051:T:C	C105R	0.998
16:31215052:G:A	C105Y	0.998
16:31224390:T:A	W357R	0.998
16:31224390:T:C	W357R	0.998
16:31224226:T:C	L302P	0.997
16:31224303:T:C	F328L	0.997
16:31224305:C:A	F328L	0.997
16:31224305:C:G	F328L	0.997
16:31224360:T:A	W347R	0.997
16:31224360:T:C	W347R	0.997
16:31224399:G:C	G360R	0.997
16:31224400:G:T	G360V	0.997
16:31224562:G:A	G414D	0.997
16:31214778:T:C	C14R	0.996
16:31222915:T:A	W277R	0.996
16:31222915:T:C	W277R	0.996
16:31224362:G:C	W347C	0.996
16:31224362:G:T	W347C	0.996
16:31224383:G:C	K354N	0.996
16:31224383:G:T	K354N	0.996
16:31224400:G:A	G360D	0.996
16:31224710:T:A	N463K	0.996
16:31224710:T:G	N463K	0.996
16:31214809:C:A	P24H	0.995
16:31214895:T:C	C53R	0.995
16:31214942:C:A	N68K	0.995
16:31214942:C:G	N68K	0.995
16:31215005:C:A	H89Q	0.995
16:31215005:C:G	H89Q	0.995
16:31215028:G:A	C97Y	0.995

dbSNP variants (sampled 300 via entrez): RS1000301104 (16:31220974 A>C,T), RS1000489485 (16:31215401 A>C), RS1000931078 (16:31222439 A>C), RS1000961838 (16:31216457 C>A,T), RS1001057180 (16:31223712 T>C), RS1001131818 (16:31223347 C>T), RS1001660355 (16:31213802 C>A), RS1001907343 (16:31227416 T>C), RS1002006397 (16:31213541 C>T), RS1002294610 (16:31215490 G>A), RS1002380984 (16:31227075 C>A,G), RS1002442338 (16:31223004 G>A,T), RS1002563537 (16:31224109 C>A,G), RS1002640819 (16:31230149 C>T), RS1003048235 (16:31223870 C>G,T)

Disease associations

OMIM: gene MIM:613288 | 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

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TU57	HAP1 TRIM72 (-) 1	Cancer cell line	Male
CVCL_TU58	HAP1 TRIM72 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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