TRIM27

Summary

TRIM27 (tripartite motif containing 27, HGNC:9975) is a protein-coding gene on chromosome 6p22.1, encoding Zinc finger protein RFP (P14373). E3 ubiquitin-protein ligase that mediates ubiquitination of various substrates and thereby plays a role in diffent processes including proliferation, innate immunity, apoptosis, immune response or autophagy.

This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the nuclear matrix. It interacts with the enhancer of polycomb protein and represses gene transcription. It is also thought to be involved in the differentiation of male germ cells. Fusion of the N-terminus of this protein with the truncated C-terminus of the RET gene product has been shown to result in production of the ret transforming protein.

Source: NCBI Gene 5987 — RefSeq curated summary.

At a glance

• GWAS associations: 44
• Clinical variants (ClinVar): 48 total
• Druggable target: yes
• MANE Select transcript: NM_006510

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9975
Approved symbol	TRIM27
Name	tripartite motif containing 27
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	RNF76
Ensembl gene	ENSG00000204713
Ensembl biotype	protein_coding
OMIM	602165
Entrez	5987

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000377194, ENST00000377199, ENST00000414543, ENST00000467742, ENST00000481474, ENST00000496091, ENST00000498117, ENST00000892674, ENST00000892675, ENST00000892676

RefSeq mRNA: 1 — MANE Select: NM_006510 NM_006510

CCDS: CCDS4654

Canonical transcript exons

ENST00000377199 — 8 exons

Exon	Start	End
ENSE00001591477	28903002	28904665
ENSE00001608493	28908808	28908840
ENSE00001735370	28907236	28907262
ENSE00001828888	28923213	28923985
ENSE00003475120	28911696	28911718
ENSE00003586559	28921892	28921987
ENSE00003634362	28908973	28909088
ENSE00003671724	28920012	28920242

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.6604 / max 297.9161, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72442	41.9204	1815
72440	4.3830	1644
72439	3.8175	1677
72441	1.4575	962
72443	1.0821	729

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.11	gold quality
body of pancreas	UBERON:0001150	95.82	gold quality
right lobe of liver	UBERON:0001114	94.45	gold quality
endometrium	UBERON:0001295	94.31	gold quality
endocervix	UBERON:0000458	94.20	gold quality
blood	UBERON:0000178	94.18	gold quality
pancreas	UBERON:0001264	94.10	gold quality
spleen	UBERON:0002106	94.10	gold quality
pituitary gland	UBERON:0000007	94.01	gold quality
adenohypophysis	UBERON:0002196	93.81	gold quality
cortical plate	UBERON:0005343	93.81	gold quality
granulocyte	CL:0000094	93.67	gold quality
liver	UBERON:0002107	93.48	gold quality
prostate gland	UBERON:0002367	93.39	gold quality
fallopian tube	UBERON:0003889	93.36	gold quality
tonsil	UBERON:0002372	93.04	gold quality
uterine cervix	UBERON:0000002	93.02	gold quality
right ovary	UBERON:0002118	92.84	gold quality
stromal cell of endometrium	CL:0002255	92.80	gold quality
left ovary	UBERON:0002119	92.77	gold quality
right lobe of thyroid gland	UBERON:0001119	92.70	gold quality
ovary	UBERON:0000992	92.69	gold quality
left lobe of thyroid gland	UBERON:0001120	92.50	gold quality
lymph node	UBERON:0000029	92.37	gold quality
myometrium	UBERON:0001296	92.35	gold quality
thyroid gland	UBERON:0002046	92.33	gold quality
body of uterus	UBERON:0009853	92.33	gold quality
left uterine tube	UBERON:0001303	92.25	gold quality
metanephros cortex	UBERON:0010533	92.20	gold quality
ectocervix	UBERON:0012249	92.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.13

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JUN	Activation

Literature-anchored findings (GeneRIF, showing 40)

• role in inducing apoptosis via its RING finger-B box-coiled-coil motif (PMID:12807881)
• the amino-terminal and carboxyl-terminal regions of Mi-2 beta have distinct transcriptional activities and bind to BRG1 and the RET finger protein, forming a multiprotein supercomplex involved in transcriptional regulation. (PMID:14530259)
• RFP selectively ablates Rb function. (PMID:15837424)
• Mi-2beta and RFP, known to be involved in transcriptional repression in the nucleus, co-localize with MCRS1 in the nucleolus and appear to activate the rRNA transcription. (PMID:16186106)
• RFP negatively regulates signaling involved in the antiviral response and inflammation by targeting the IKKs. (PMID:16393995)
• Our study is the first in the literature to show expression of RET finger protein in patients with breast carcinoma (PMID:19232840)
• These findings provide a unique mechanism for regulating class II PI3Ks, and identify TRIM27 as a previously undescribed negative regulator of CD4 T cells. (PMID:22128329)
• TRIM27 expression is a modifier of cancer incidence and progression and is a potential target for intervention. (PMID:22556269)
• Data conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases. (PMID:22829933)
• RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a predictive marker for chemoresistance in ovarian cancer patients. (PMID:23342271)
• RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation. (PMID:23419514)
• These findings provide a cellular and molecular function for MAGE-L2-TRIM27 in retrograde transport, including an unappreciated role of K63-linked ubiquitination and identification of an activating signal of the WASH regulatory complex. (PMID:23452853)
• The neoplasm leading cell specific expression of integrin beta1 was posttranscriptionally regulated by the TRIM27/MRTF-B complex in response to the loss of intercellular adhesion. (PMID:24794433)
• Study found that compared to healthy individuals, Trim27 was significantly upregulated in patients with Parkinson’s disease (PMID:25223908)
• Authors observed rapid, ICP0-dependent loss of TRIM27 during HSV-1 infection. (PMID:25320289)
• Studied the expression of TRIM27 in normal ovarian and fallopian tube epithelial cells and in ovarian serous carcinoma cells; correlated TRIM27 expression with clinical and pathological parameters. (PMID:26568293)
• Results demonstrated that TRIM27 restricts the intracellular survival of mycobacteria, suggesting that it is a potential host restriction factor for Mycobacterium tuberculosis by enhancing host immune-inflammatory responses mediated by JNK/p38 pathways as well as cell apoptosis. (PMID:27698396)
• RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). (PMID:28155970)
• findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1. (PMID:29688809)
• Results showed that TRIM27 was upregulated in colorectal cancer (CRC) tissues, and significantly associated with tumor invasion, metastasis and prognosis. Following TRIM27 inhibition and overexpression in CRC cells, it was found that TRIM27 promoted cell proliferation, possibly via the inhibition of apoptosis and cell cycle regulation. These results suggested that TRIM27 is an oncogenic protein in the progression of CRC. (PMID:29767249)
• The roles of Trim27 in hematopoiesis were studied by enforcing its expression in human hematopoietic stem and progenitor cells. Trim27 up-regulated essential regulators of myelopoiesis. The myeloproliferative advantage caused by overexpressing Trim27/TRIM27 is conserved between mouse and human hematopoiesis. (PMID:29897614)
• NCOA4-RET as the dominant fusion in intercalated duct type salivary gland intraductal carcinoma. A subset of IC patients with apocrine variant IC harbor a novel TRIM27-RET. (PMID:30045065)
• The study suggests that RFP contributes to chemoresistance in glioblastoma via aberrant deacetylation of histone H3 at K27. (PMID:30811978)
• Tumor-type-specific NCOA4-RET or TRIM27-RET translocations are found in a subset of widely invasive salivary carcinomas with intercalated duct-like immunoprofiles. (PMID:31162284)
• TRIM27 expression is significantly increased by IL-6 and suggest a TRIM27/STAT3-dependent mechanism. (PMID:31747314)
• Tripartite Motif-Containing 27 Attenuates Liver Ischemia/Reperfusion Injury by Suppressing Transforming Growth Factor beta-Activated Kinase 1 (TAK1) by TAK1 Binding Protein 2/3 Degradation. (PMID:32343849)
• Downregulation of TRIM27 suppresses gastric cancer cell proliferation via inhibition of the Hippo-BIRC5 pathway. (PMID:32825933)
• TRIM27 acts as an oncogene and regulates cell proliferation and metastasis in non-small cell lung cancer through SIX3-beta-catenin signaling. (PMID:33264103)
• Tri-domain proteins 27 reduce inflammation and apoptosis in HK-2 cells and protect against acute kidney injury in mice. (PMID:33336745)
• TRIM27-mediated ubiquitination of PPARgamma promotes glutamate-induced cell apoptosis and inflammation. (PMID:33385414)
• Epigenetic-smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early-stage NSCLC patients. (PMID:33448640)
• TRIM27 contributes to glomerular endothelial cell injury in lupus nephritis by mediating the FoxO1 signaling pathway. (PMID:33854173)
• TRIM27 interacts with Ikappabalpha to promote the growth of human renal cancer cells through regulating the NF-kappaB pathway. (PMID:34284744)
• [Mechanism of TRIM27 promoting inflammatory response in lung cancer cells]. (PMID:34695898)
• Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC. (PMID:34932879)
• TRIM27 regulates the expression of PDCD4 by the ubiquitinproteasome pathway in ovarian and endometrial cancer cells. (PMID:35583010)
• TRIM27 cooperates with STK38L to inhibit ULK1-mediated autophagy and promote tumorigenesis. (PMID:35670107)
• TRIM27-USP7 complex promotes tumour progression via STAT3 activation in human hepatocellular carcinoma. (PMID:35753056)
• Analysis of TRIM27 prognosis value and immune infiltrates in hepatocellular carcinoma. (PMID:36217828)
• CLEC16A interacts with retromer and TRIM27, and its loss impairs endosomal trafficking and neurodevelopment. (PMID:36538041)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim27	ENSMUSG00000021326
rattus_norvegicus	Trim27	ENSRNOG00000055917

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

Zinc finger protein RFP — P14373 (reviewed: P14373)

Alternative names: RING finger protein 76, Ret finger protein, Tripartite motif-containing protein 27

All UniProt accessions (3): A0A1U9X8R9, P14373, H0Y551

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates ubiquitination of various substrates and thereby plays a role in diffent processes including proliferation, innate immunity, apoptosis, immune response or autophagy. Ubiquitinates PIK3C2B and inhibits its activity by mediating the formation of ‘Lys-48’-linked polyubiquitin chains; the function inhibits CD4 T-cell activation. Acts as a regulator of retrograde transport: together with MAGEL2, mediates the formation of ‘Lys-63’-linked polyubiquitin chains at ‘Lys-220’ of WASHC1, leading to promote endosomal F-actin assembly. Has a transcriptional repressor activity by cooperating with EPC1. Induces apoptosis by activating Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity independently of mitochondrial events. May function in male germ cell development. Has DNA-binding activity and preferentially bound to double-stranded DNA. Forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which in turn deubiquitinates RIPK1 resulting in the positive regulation of TNF-induced apoptosis. In addition, acts with USP7 or PTPN11 as an inhibitor of the antiviral signaling pathway by promoting kinase TBK1 ubiquitination and degradation. Acts as a negative regulator of NOD2 signaling by mediating ubiquitination of NOD2, promoting its degradation by the proteasome. Alternatively, facilitates mitophagy via stabilization of active TBK1. Negatively regulates autophagy flux under basal conditions by directly polyubiquitinating ULK1. During starvation-induced autophagy, catalyzes non-degradative ubiquitination of the kinase STK38L promoting its activation and phosphorylation of ULK1 leading to its ubiquitination and degradation to restrain the amplitude and duration of autophagy. (Microbial infection) Positively regulates hepatitis C virus replication by suppressing type I IFN response during infection.

Subunit / interactions. Homomultimerizes. Part of a complex consisting of TRIM27, USP7 and MAGEL2; directly interacts with USP7. Interacts with PML, EIF3S6, EPC1, CHD4 and EID1. Interacts with MAGED4, MAGEF1 and MAGEL2. Interacts with PTPN11. Interacts with autophagy receptor p62/SQSTM1. (Microbial infection) Interacts with M.tuberculosis PtpA, whick blocks TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis. (Microbial infection) Interacts with herpes simplex virus protein ICP0.

Subcellular location. Nucleus. Cytoplasm. PML body. Early endosome. Mitochondrion.

Tissue specificity. Expressed in testis namely within the seminiferous tubules.

Disease relevance. A chromosomal aberration involving TRIM27/RFP is found in papillary thyroid carcinomas (PTCs). Translocation t(6;10)(p21.3;q11.2) with RET. The translocation generates TRIM27/RET and delta TRIM27/RET oncogenes.

Domain organisation. The coiled-coil region mediates interaction with EPC1 and CHD4. The B box and coiled-coil domains mediate interaction with PML. The B box and the distal coiled-coil domains mediate homomultimerisation. The B30.2 domain mediates interaction with EIF3S6.

Induction. By type I interferons and upon hepatitis C viral infection.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
P14373-1	Alpha	yes
P14373-2	Beta

RefSeq proteins (1): NP_006501* (*=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
IPR020457	Znf_B-box_chordata	Domain
IPR035791	SPRY/PRY_TRIM27	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13765, PF15227

UniProt features (16 total): binding site 4, splice variant 2, mutagenesis site 2, zinc finger region 2, coiled-coil region 2, chain 1, domain 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14373-F1	89.04	0.73

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 (1): 315–316 (breakpoint for translocation to form the trim27/ret oncogene)

Ligand- & substrate-binding residues (4): 96; 99; 118; 124

Mutagenesis-validated functional residues (2):

Position	Phenotype
16	abolished e3 ubiquitin-protein ligase activity; when associated with a-31.
31	abolished e3 ubiquitin-protein ligase activity; when associated with a-16.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-8948751	Regulation of PTEN stability and activity
R-HSA-9635465	Suppression of apoptosis

MSigDB gene sets: 240 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, MORF_ATRX, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_PEPTIDYL_LYSINE_MODIFICATION

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), spermatogenesis (GO:0007283), negative regulation of autophagy (GO:0010507), protein sumoylation (GO:0016925), negative regulation of type I interferon production (GO:0032480), negative regulation of viral transcription (GO:0032897), Arp2/3 complex-mediated actin nucleation (GO:0034314), retrograde transport, endosome to Golgi (GO:0042147), suppression of viral release by host (GO:0044790), innate immune response (GO:0045087), negative regulation of gene expression, epigenetic (GO:0045814), positive regulation of actin nucleation (GO:0051127), protein K63-linked ubiquitination (GO:0070534), positive regulation of autophagy (GO:0010508), protein ubiquitination (GO:0016567), positive regulation of type I interferon production (GO:0032481), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (12): nucleic acid binding (GO:0003676), DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), SUMO transferase activity (GO:0019789), identical protein binding (GO:0042802), metal ion binding (GO:0046872), ubiquitin protein ligase activity (GO:0061630), phosphatidylinositol 3-kinase inhibitor activity (GO:0141039), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (12): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endosome (GO:0005768), early endosome (GO:0005769), cytosol (GO:0005829), PML body (GO:0016605), nuclear membrane (GO:0031965), retromer complex (GO:0030904)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
PTEN Regulation	1
Response of Mtb to phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
autophagy	2
regulation of autophagy	2
protein modification by small protein conjugation	2
regulation of type I interferon production	2
type I interferon production	2
actin nucleation	2
binding	2
ubiquitin-like protein transferase activity	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cytoplasm	2
endomembrane system	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
developmental process involved in reproduction	1
male gamete generation	1
negative regulation of catabolic process	1
peptidyl-lysine modification	1
negative regulation of cytokine production	1
viral transcription	1
regulation of viral transcription	1
negative regulation of viral process	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
defense response to virus	1
immune response	1
defense response to symbiont	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
regulation of actin nucleation	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
protein polyubiquitination	1
positive regulation of catabolic process	1
positive regulation of cytokine production	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

1531 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM27	MAGEL2	Q9UJ55	950
TRIM27	USP7	Q93009	898
TRIM27	CHD4	Q14839	863
TRIM27	BBOX1	O75936	857
TRIM27	TRAT1	Q6PIZ9	841
TRIM27	SIGLEC1	Q9BZZ2	805
TRIM27	CHUK	O15111	805
TRIM27	TRIM28	Q13263	760
TRIM27	IKBKE	Q14164	738
TRIM27	RET	P07949	729
TRIM27	TRIM24	O15164	728
TRIM27	IKBKB	O14920	722
TRIM27	MCRS1	Q96EZ8	716
TRIM27	PML	P29590	696
TRIM27	PRY	O14603	685

IntAct

1442 interactions, top by confidence:

A	B	Type	Score
TRIM27	NDEL1	psi-mi:“MI:0915”(physical association)	0.840
ARHGEF3	TRIM27	psi-mi:“MI:0915”(physical association)	0.830
ZGPAT	TRIM27	psi-mi:“MI:0915”(physical association)	0.810
PRPF31	TRIM27	psi-mi:“MI:0915”(physical association)	0.790
TRIM27	PSMB1	psi-mi:“MI:0915”(physical association)	0.790
GPANK1	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	POLE2	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	NR1D2	psi-mi:“MI:0915”(physical association)	0.780
PPP1R18	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	ATOSB	psi-mi:“MI:0915”(physical association)	0.780
ZNF417	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
BAG1	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
VPS25	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
PUS7L	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	ABCF3	psi-mi:“MI:0915”(physical association)	0.780
BABAM1	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	EIF4E	psi-mi:“MI:0915”(physical association)	0.740
TRIM27	CCDC102B	psi-mi:“MI:0915”(physical association)	0.720
CWF19L2	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	STK25	psi-mi:“MI:0915”(physical association)	0.720
POLR1C	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
EIF3D	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	NCK2	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	NUDT21	psi-mi:“MI:0915”(physical association)	0.720
USP2	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	SNRPB2	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	SNRPA	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	GFAP	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	XPA	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (773): TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid), TRIM27 (Two-hybrid)

ESM2 similar proteins: A0JN74, A6NCK2, A6NGJ6, A6NI03, B1H278, K7N6K2, O00478, O00481, P14373, P19474, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2YEM8, Q2YEM9, Q3ZEE5, Q587N6, Q5C8T6, Q5C8T8, Q5C8U1, Q5D7I9, Q5D7J0, Q5D7J1, Q5NCC9, Q5R996, Q62158, Q6MFZ5, Q7YR33, Q7YRV4, Q80V85, Q8BGE7, Q8NG06, Q923T7, Q96BQ3, Q96F44, Q99PP6, Q99PQ2

Diamond homologs: A0A2P1BRP3, A0A2P1BRQ0, A0JN74, A0ZSK3, A0ZSK4, B1H278, O19085, O95361, P14373, P19474, Q02084, Q1XHU0, Q309B1, Q5R760, Q5R7W8, Q62158, Q62556, Q7KYR7, Q86WT6, Q8N7C3, Q8WVV5, Q91431, Q91453, Q96F44, Q98989, Q98993, Q99PP9, Q99PQ2, Q9C029, Q9HCM9, Q9JLN5, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NK02, A6NLI5, C9J1S8, K7N6K2, O00635

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
TRIM27	up-regulates	Apoptosis
TRIM27	up-regulates	MAPK11
TRIM27	up-regulates	MAPK12
TRIM27	up-regulates	MAPK13
TRIM27	up-regulates	MAPK14
TRIM27	up-regulates	MAPK8
TRIM27	down-regulates	PIK3C2B	ubiquitination
MAGEL2	“up-regulates activity”	TRIM27	binding
TRIM27	“up-regulates activity”	WASHC1	ubiquitination
TRIM27	up-regulates	Cell_death
TRIM27	up-regulates	p38
Ub:E2	“up-regulates activity”	TRIM27	ubiquitination
TRIM27	“down-regulates quantity by destabilization”	PPARG	ubiquitination
miR-183	“down-regulates quantity by destabilization”	TRIM27	“post transcriptional regulation”
TRIM27	“up-regulates activity”	STK38L	ubiquitination
TRIM27	“down-regulates quantity”	ULK1	ubiquitination
TRIM27	“down-regulates quantity by destabilization”	ULK1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1056 predictions. Top by Δscore:

Variant	Effect	Δscore
6:28904662:TCCA:T	acceptor_gain	1.0000
6:28904663:CCA:C	acceptor_gain	1.0000
6:28904663:CCAC:C	acceptor_gain	1.0000
6:28904664:CA:C	acceptor_gain	1.0000
6:28904664:CACT:C	acceptor_loss	1.0000
6:28904664:CACTG:C	acceptor_gain	1.0000
6:28904665:ACTGT:A	acceptor_loss	1.0000
6:28904666:C:CC	acceptor_gain	1.0000
6:28904666:CTGTA:C	acceptor_loss	1.0000
6:28920006:CCTTA:C	donor_loss	1.0000
6:28920007:CTTAC:C	donor_loss	1.0000
6:28920008:TTAC:T	donor_loss	1.0000
6:28920009:TACC:T	donor_loss	1.0000
6:28920010:A:C	donor_loss	1.0000
6:28920011:C:A	donor_loss	1.0000
6:28920241:CT:C	acceptor_gain	1.0000
6:28920243:C:CC	acceptor_gain	1.0000
6:28920245:A:C	acceptor_gain	1.0000
6:28920266:A:T	acceptor_gain	1.0000
6:28921886:CCTTA:C	donor_loss	1.0000
6:28921887:CTTA:C	donor_loss	1.0000
6:28921888:TTACC:T	donor_loss	1.0000
6:28921889:TA:T	donor_loss	1.0000
6:28921891:C:CT	donor_loss	1.0000
6:28921908:G:A	donor_gain	1.0000
6:28921985:CTC:C	acceptor_gain	1.0000
6:28921988:C:CC	acceptor_gain	1.0000
6:28923207:CCTCA:C	donor_loss	1.0000
6:28923208:CTCA:C	donor_loss	1.0000
6:28923209:TCA:T	donor_loss	1.0000

AlphaMissense

3376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:28904465:A:G	W383R	0.999
6:28904465:A:T	W383R	0.999
6:28904550:G:C	F354L	0.999
6:28904550:G:T	F354L	0.999
6:28904552:A:G	F354L	0.999
6:28923290:A:G	C115R	0.999
6:28904493:C:A	W373C	0.998
6:28904493:C:G	W373C	0.998
6:28904495:A:G	W373R	0.998
6:28904495:A:T	W373R	0.998
6:28923289:C:T	C115Y	0.998
6:28923587:A:G	C16R	0.998
6:28904430:T:A	R394S	0.997
6:28904430:T:G	R394S	0.997
6:28904456:C:G	G386R	0.997
6:28923280:C:G	C118S	0.997
6:28923281:A:G	C118R	0.997
6:28923281:A:T	C118S	0.997
6:28923288:G:C	C115W	0.997
6:28904191:A:G	F474S	0.996
6:28904229:G:C	F461L	0.996
6:28904229:G:T	F461L	0.996
6:28904231:A:G	F461L	0.996
6:28904265:G:C	F449L	0.996
6:28904265:G:T	F449L	0.996
6:28904266:A:G	F449S	0.996
6:28904267:A:G	F449L	0.996
6:28904448:A:C	C388W	0.996
6:28904455:C:A	G386V	0.996
6:28904455:C:T	G386D	0.996

dbSNP variants (sampled 300 via entrez): RS1000001217 (6:28906740 A>T), RS1000093868 (6:28922861 G>T), RS1000185611 (6:28912830 G>C), RS1000392625 (6:28924119 C>T), RS1000945893 (6:28919865 T>A,C), RS1001021802 (6:28918524 CAAAAAT>C), RS1001098924 (6:28924168 C>T), RS1001113684 (6:28913935 T>G), RS1001150873 (6:28913770 T>C), RS1001288971 (6:28920830 A>G), RS1001393446 (6:28921311 C>T), RS1001464388 (6:28909402 C>A,T), RS1001559191 (6:28909678 T>C), RS1001586303 (6:28912180 G>C), RS1001638471 (6:28911760 A>G)

Disease associations

OMIM: gene MIM:602165 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST000693_9	Platelet aggregation	2.000000e-06
GCST002194_1	Social communication problems	3.000000e-07
GCST002986_3	Childhood and early adolescence aggressive behavior	2.000000e-06
GCST003518_57	Daytime sleep phenotypes	7.000000e-07
GCST003518_58	Daytime sleep phenotypes	1.000000e-06
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_212	Autism spectrum disorder or schizophrenia	5.000000e-14
GCST004521_43	Autism spectrum disorder or schizophrenia	2.000000e-27
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_58	Autism spectrum disorder or schizophrenia	1.000000e-17
GCST004521_7	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_73	Autism spectrum disorder or schizophrenia	8.000000e-11
GCST004521_84	Autism spectrum disorder or schizophrenia	1.000000e-12
GCST004521_91	Autism spectrum disorder or schizophrenia	1.000000e-11
GCST004749_78	Lung cancer in ever smokers	6.000000e-08
GCST004866_25	Alopecia areata	9.000000e-07
GCST005212_37	Asthma	6.000000e-07
GCST005541_5	Sarcoidosis (Lofgren’s syndrome vs non-Lofgren’s syndrome)	4.000000e-19
GCST005830_109	Hand grip strength	3.000000e-11
GCST006862_1	Asthma	5.000000e-09
GCST006940_46	Neurociticism	8.000000e-10
GCST006943_41	Feeling miserable	1.000000e-08
GCST006944_40	Experiencing mood swings	8.000000e-09
GCST006979_497	Heel bone mineral density	5.000000e-10
GCST007201_363	Schizophrenia	7.000000e-23
GCST007325_296	General risk tolerance (MTAG)	2.000000e-16
GCST008746_11	Estimated glomerular filtration rate in diabetes	3.000000e-09
GCST008758_33	Pre-treatment viral load in HIV-1 infection	9.000000e-16
GCST008916_89	Asthma	2.000000e-10
GCST008921_4	Asthma and major depressive disorder	2.000000e-11

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005427	social communication impairment
EFO:0007828	daytime rest measurement
EFO:0006941	grip strength measurement
EFO:0007660	neuroticism measurement
EFO:0009598	feeling miserable measurement
EFO:0008475	mood instability measurement
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0010125	viral load
EFO:0004509	hemoglobin measurement
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725067 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases methylation	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	decreases expression	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
trichostatin A	affects expression	1
butyraldehyde	increases methylation	1
caprylic aldehyde	increases methylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
pentanal	increases methylation	1
heptanal	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dinitrofluorobenzene	increases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697485	Binding	Inhibition of TRIM27 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TU00	HAP1 TRIM27 (-) 1	Cancer cell line	Male
CVCL_TU01	HAP1 TRIM27 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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