TRIM37

Summary

TRIM37 (tripartite motif containing 37, HGNC:7523) is a protein-coding gene on chromosome 17q22, encoding E3 ubiquitin-protein ligase TRIM37 (O94972). E3 ubiquitin-protein ligase required to prevent centriole reduplication. It is a selective cancer dependency (DepMap: 27.5% of cell lines).

This gene encodes a member of the tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein-protein and/or protein-nucleic acid interactions. Mutations in this gene are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of mesodermal origin. TRIM37 localizes in peroxisomal membranes, and has been implicated in human peroxisomal biogenesis disorders.

Source: NCBI Gene 4591 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mulibrey nanism (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 843 total — 49 pathogenic, 55 likely-pathogenic
• Phenotypes (HPO): 46
• Cancer dependency (DepMap): dependent in 27.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_015294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7523
Approved symbol	TRIM37
Name	tripartite motif containing 37
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0898, POB1, TEF3
Ensembl gene	ENSG00000108395
Ensembl biotype	protein_coding
OMIM	605073
Entrez	4591

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 49 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000262294, ENST00000393065, ENST00000393066, ENST00000577554, ENST00000580122, ENST00000580620, ENST00000580973, ENST00000581468, ENST00000582852, ENST00000583387, ENST00000583945, ENST00000584889, ENST00000585287, ENST00000625984, ENST00000885243, ENST00000885244, ENST00000885245, ENST00000885246, ENST00000885247, ENST00000885248, ENST00000885249, ENST00000885250, ENST00000885251, ENST00000885252, ENST00000885253, ENST00000885254, ENST00000885255, ENST00000885256, ENST00000885257, ENST00000885258, ENST00000885259, ENST00000885260, ENST00000938624, ENST00000938625, ENST00000938626, ENST00000938627, ENST00000938628, ENST00000938629, ENST00000938630, ENST00000938631, ENST00000938632, ENST00000938633, ENST00000938634, ENST00000938635, ENST00000938636, ENST00000938637, ENST00000964646, ENST00000964647, ENST00000964648, ENST00000964649, ENST00000964650, ENST00000964651, ENST00000964652, ENST00000964653, ENST00000964654

RefSeq mRNA: 11 — MANE Select: NM_015294 NM_001005207, NM_001320987, NM_001320988, NM_001320989, NM_001320990, NM_001353082, NM_001353083, NM_001353084, NM_001353085, NM_001353086, NM_015294

CCDS: CCDS32694, CCDS45746, CCDS82174

Canonical transcript exons

ENST00000262294 — 24 exons

Exon	Start	End
ENSE00000739598	59001598	59001714
ENSE00002704583	58998202	58999459
ENSE00002732324	59106441	59106880
ENSE00003471631	59047683	59047819
ENSE00003483061	59056875	59057054
ENSE00003500036	59017296	59017424
ENSE00003500739	59070823	59070947
ENSE00003508073	59075647	59075714
ENSE00003533683	59088291	59088407
ENSE00003543708	59079754	59079877
ENSE00003550396	59051214	59051328
ENSE00003554029	59041813	59041898
ENSE00003555643	59031896	59032090
ENSE00003556004	59049178	59049393
ENSE00003566820	59081097	59081219
ENSE00003571327	59084002	59084089
ENSE00003578408	59104293	59104394
ENSE00003579579	59028415	59028723
ENSE00003604929	59061032	59061108
ENSE00003629848	59015610	59015799
ENSE00003654988	59062567	59062648
ENSE00003665168	59064355	59064405
ENSE00003675505	59012328	59012446
ENSE00003692694	59091300	59091340

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.0932 / max 528.5830, expressed in 1809 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167321	16.3772	1683
167319	14.0562	1767
167318	1.9919	772
167320	1.5079	512
167317	0.8214	311
167314	0.1832	91
167316	0.1553	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.28	gold quality
endometrium epithelium	UBERON:0004811	99.23	gold quality
secondary oocyte	CL:0000655	98.87	gold quality
sperm	CL:0000019	98.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.81	gold quality
middle temporal gyrus	UBERON:0002771	98.44	gold quality
male germ cell	CL:0000015	98.37	gold quality
postcentral gyrus	UBERON:0002581	98.05	gold quality
pons	UBERON:0000988	97.96	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.92	gold quality
parietal lobe	UBERON:0001872	97.83	gold quality
superior frontal gyrus	UBERON:0002661	97.61	gold quality
frontal pole	UBERON:0002795	97.31	gold quality
cerebellar vermis	UBERON:0004720	97.28	gold quality
orbitofrontal cortex	UBERON:0004167	97.25	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.06	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.03	gold quality
entorhinal cortex	UBERON:0002728	96.94	gold quality
occipital lobe	UBERON:0002021	96.49	gold quality
superior vestibular nucleus	UBERON:0007227	96.44	gold quality
primary visual cortex	UBERON:0002436	96.41	gold quality
CA1 field of hippocampus	UBERON:0003881	95.82	gold quality
paraflocculus	UBERON:0005351	95.38	gold quality
medulla oblongata	UBERON:0001896	94.85	gold quality
prefrontal cortex	UBERON:0000451	94.81	gold quality
substantia nigra pars compacta	UBERON:0001965	94.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.54	gold quality
left testis	UBERON:0004533	94.42	gold quality
right testis	UBERON:0004534	94.32	gold quality
choroid plexus epithelium	UBERON:0003911	94.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting TRIM37, 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-3692-3P	99.98	70.27	2139
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 27.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 38)

• The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder (PMID:11938494)
• novel splice variants observed in lymphoblastoid cells and muscle tissue of normal subjects and mulibrey nanism patients (PMID:12754710)
• The TRIM37 acts as a TRIM domain-dependent E3 ubiquitin ligase and imply defective ubiquitin-dependent degradation of an as-yet-unidentified target protein in the pathogenesis of mulibrey nanism. (PMID:15885686)
• Functional link of TRIM37 to the ubiquitin-proteosome pathway may provide novel clues to the development of metabolic syndrome. (PMID:16306379)
• TRIM37 expression is regulated by several mechanisms: through nonsense surveillance of non-functional transcripts, as well as through 3’UTR regulatory sequences and/or naturally occurring antisense RNAs especially in testis. (PMID:16310976)
• Novel mutations in the tumor necrosis factor receptor associated factor (TRAF) domain alter the subcellular localization of TRIM37, and are associated with Wilm’s tumor in a patient with mulibrey nanism. (PMID:17100991)
• Mutation screening of the TRIM37 gene revealed that the proband had a homozygous two base pair deletion, c.1894_1895delGA, resulting in a frame-shift and a premature termination codon. (PMID:17551331)
• inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas. (PMID:19329943)
• Our report underlines the necessity of early clinical diagnosis of Mulibrey nanism. Careful cardiologic examination is required to detect constrictive pericarditis, which is a major factor of mortality in these patients (PMID:23385855)
• In this study, authors demonstrate that human Trim 37 possesses anti-HIV-1 activity. (PMID:24317724)
• results reveal TRIM37 as an oncogenic H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and promotes transformation by facilitating silencing of tumour suppressors and other genes. (PMID:25470042)
• These finding may provide insight into the understanding of TRIM37 as a novel critical factor of HCC and a candidate target for HCC treatment. (PMID:26208456)
• The oncogenic roles of TRIM37 in pancreatic cancer. (PMID:26395261)
• knockdown of TRIM37 markedly downregulated the expression of beta-catenin, cyclin D1, and c-Myc in CRC cells. These results suggest that knockdown of TRIM37 inhibits proliferation and tumorigenesis by the inactivation of Wnt/beta-catenin signaling in CRC cells. (PMID:28081740)
• TRIM37 was overexpressed in human CRC tissues. High TRIM37 expression resulted in increased CRC proliferation, migration and invasion. Mechanistically, it was confirmed that TRIM37 enhanced invasion and metastasis of CRC via the epithelialmesenchymal transition pathway. (PMID:28098873)
• TRIM37-mediated ubiquitylation stabilizes PEX5 and promotes peroxisomal matrix protein import, suggesting that mulibrey nanism is a new peroxisomal biogenesis disorder. (PMID:28724525)
• TRIM37 mutation is associated with mulibrey nanism. (PMID:28815877)
• TRIM37 functions as an oncogene in the development and progression of glioma. (PMID:29324313)
• This study unveils a positive role of TRIM37 in regulating the MTORC1-TFEB axis. (PMID:29940807)
• TRIM37 bound to TRAF2 and induced K63-linked ubiquitination of TRAF2, sustaining the eventual activation of the NF-kappaB pathway, promoting the aggressiveness of non-small-cell lung cancer cells. (PMID:30043491)
• Genotoxic stress-activates ATM kinase directly interacted with and phosphorylated TRIM37 in the cytoplasm, which induced translocation of TRIM37 into the nucleus, where it formed a complex with NEMO and TRAF6 via a TRAF6-binding motif (TBM) (PMID:30254148)
• TRIM37 has a role in apoptosis and IL-1beta release in mouse BV-2 microglia that involves PPARgamma ubiquitination; it is increased in mononuclear leukocytes of intracerebral hemorrhage patients (PMID:31301768)
• Ginkgolide B protects human pulmonary alveolar epithelial A549 cells from lipopolysaccharide-induced inflammatory responses by reducing TRIM37-mediated NF-kappaB activation. (PMID:31691373)
• TRIM37 is highly expressed during mitosis in CHON-002 chondrocytes cell line and is regulated by miR-223. (PMID:32353567)
• ASB16-AS1 up-regulated and phosphorylated TRIM37 to activate NF-kappaB pathway and promote proliferation, stemness, and cisplatin resistance of gastric cancer. (PMID:32572790)
• Oncogenic TRIM37 Links Chemoresistance and Metastatic Fate in Triple-Negative Breast Cancer. (PMID:32855208)
• TRIM37 controls cancer-specific vulnerability to PLK4 inhibition. (PMID:32908304)
• Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer. (PMID:32908313)
• TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin. (PMID:33491649)
• Circular RNA circRNA_101996 promoted cervical cancer development by regulating miR-1236-3p/TRIM37 axis. (PMID:33728810)
• TRIM37 negatively regulates inflammatory responses induced by virus infection via controlling TRAF6 ubiquitination. (PMID:33839419)
• TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity. (PMID:33983387)
• TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner. (PMID:34130705)
• TRIM37 Promotes Pancreatic Cancer Progression through Modulation of Cell Growth, Migration, Invasion, and Tumor Immune Microenvironment. (PMID:35163097)
• Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism). (PMID:35220664)
• TRIM37 Augments AP-2gamma Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression. (PMID:35864973)
• TRIM37 promotes the aggressiveness of ovarian cancer cells and increases c-Myc expression by binding to HUWE1. (PMID:35921902)
• TRIM37 interacts with EZH2 to epigenetically suppress PTCH1 and regulate stemness in glioma stem cells through sonic hedgehog pathway. (PMID:38884661)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim37	ENSDARG00000076473
mus_musculus	Trim37	ENSMUSG00000018548
rattus_norvegicus	Trim37	ENSRNOG00000006248

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), 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), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRIM37 — O94972 (reviewed: O94972)

Alternative names: Mulibrey nanism protein, RING-type E3 ubiquitin transferase TRIM37, Tripartite motif-containing protein 37

All UniProt accessions (8): O94972, J3KS72, J3KT32, J3KT90, J3QRK3, J3QSA0, J3QSF6, J3QSH5

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase required to prevent centriole reduplication. Probably acts by ubiquitinating positive regulators of centriole reduplication. Mediates monoubiquitination of ‘Lys-119’ of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression: associates with some Polycomb group (PcG) multiprotein PRC2-like complex and mediates repression of target genes. Also acts as a positive regulator of peroxisome import by mediating monoubiquitination of PEX5 at ‘Lys-472’: monoubiquitination promotes PEX5 stabilitation by preventing its polyubiquitination and degradation by the proteasome. Has anti-HIV activity.

Subunit / interactions. Associates with the PRC2/EED-EZH2 complex.

Subcellular location. Chromosome. Cytoplasm. Perinuclear region. Peroxisome membrane.

Tissue specificity. Ubiquitous. Highly expressed in testis, while it is weakly expressed in other tissues.

Post-translational modifications. Auto-ubiquitinated.

Disease relevance. Mulibrey nanism (MUL) [MIM:253250] An autosomal recessive growth disorder characterized by severe growth failure of prenatal onset, constrictive pericardium and progressive cardiomyopathy, facial dysmorphism, and failure of sexual maturation. Additional clinical features include hepatomegaly, muscle hypotonia, J-shaped sella turcica, yellowish dots in the ocular fundi, hypoplasia of various endocrine glands, insulin resistance with type 2 diabetes, and an increased risk for Wilms’ tumor. The disease is caused by variants affecting the gene represented in this entry.

Induction. Overexpressed in a number of breast cancer cell lines.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. Acts as a proto-oncogene via its ability to monoubiquitinate ‘Lys-119’ of histone H2A (H2AK119Ub): overexpressed in a number of breast cancers and promotes transformation of cells by mediating silencing of tumor suppressor genes.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (3)

UniProt ID	Names	Canonical?
O94972-1	1, TRIM37a, TRIM37b	yes
O94972-2	2
O94972-3	3

RefSeq proteins (11): NP_001005207, NP_001307916, NP_001307917, NP_001307918, NP_001307919, NP_001340011, NP_001340012, NP_001340013, NP_001340014, NP_001340015, NP_056109* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR002083	MATH/TRAF_dom	Domain
IPR003649	Bbox_C	Domain
IPR008974	TRAF-like	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR037299	TRIM37_MATH	Domain
IPR053003	TRIM_RBCC_E3_ubiq-ligases	Family

Pfam: PF00643, PF22486

UniProt features (48 total): compositionally biased region 7, sequence variant 6, region of interest 5, binding site 4, helix 4, coiled-coil region 3, splice variant 3, sequence conflict 3, turn 3, zinc finger region 2, modified residue 2, mutagenesis site 2, strand 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3LRQ	X-RAY DIFFRACTION	2.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94972-F1	64.93	0.39

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 (4): 95; 98; 117; 124

Post-translational modifications (2): 1, 454

Mutagenesis-validated functional residues (2):

Position	Phenotype
18	abolishes ability to monoubiquitinate ’lys-119’ of histone h2a (h2ak119ub).
35–36	reduces ubiquitination and abolishes the formation of perinuclear aggregates.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 397 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GCM_MAP4K4, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, CMYB_01, GOZGIT_ESR1_TARGETS_DN, TAL1ALPHAE47_01, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), protein monoubiquitination (GO:0006513), protein import into peroxisome matrix (GO:0016558), negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of centriole replication (GO:0046600), protein stabilization (GO:0050821), protein autoubiquitination (GO:0051865), aggresome assembly (GO:0070842), protein ubiquitination (GO:0016567), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (13): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), ubiquitin-protein transferase activity (GO:0004842), tumor necrosis factor receptor binding (GO:0005164), zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), protein homodimerization activity (GO:0042803), ubiquitin protein ligase activity (GO:0061630), histone H2AK119 ubiquitin ligase activity (GO:0140862), protein binding (GO:0005515), transferase activity (GO:0016740), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (9): chromosome (GO:0005694), cytoplasm (GO:0005737), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), aggresome (GO:0016235), ESC/E(Z) complex (GO:0035098), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein ubiquitination	2
binding	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
peroxisomal membrane transport	1
protein transmembrane import into intracellular organelle	1
protein localization to peroxisome	1
establishment of protein localization to peroxisome	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
centriole replication	1
negative regulation of centrosome duplication	1
regulation of centriole replication	1
negative regulation of organelle assembly	1
regulation of protein stability	1
inclusion body assembly	1
protein modification by small protein conjugation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
ubiquitin-like protein transferase activity	1
tumor necrosis factor receptor superfamily binding	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
identical protein binding	1
protein dimerization activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
histone H2A ubiquitin ligase activity	1
catalytic activity	1
protein binding	1
cation binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
microbody	1

Protein interactions and networks

STRING

2075 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM37	PEX5	P50542	743
TRIM37	PEX5L	Q8IYB4	738
TRIM37	BBOX1	O75936	727
TRIM37	PEX1	O43933	708
TRIM37	RBCK1	Q9BYM8	707
TRIM37	PEX7	O00628	698
TRIM37	TRAT1	Q6PIZ9	581
TRIM37	TRIM11	Q96F44	536
TRIM37	TRIM33	Q9UPN9	498
TRIM37	TRIM59	Q8IWR1	491
TRIM37	TRAF1	Q13077	485
TRIM37	PLK4	O00444	482
TRIM37	KLHL42	Q9P2K6	480
TRIM37	SCARB2	Q14108	474
TRIM37	TRIM23	P36406	473

IntAct

218 interactions, top by confidence:

A	B	Type	Score
BYSL	TRIM37	psi-mi:“MI:0915”(physical association)	0.780
TRIM37	BYSL	psi-mi:“MI:0915”(physical association)	0.780
TRIM37	PNKP	psi-mi:“MI:0915”(physical association)	0.740
TRIM37	PNKP	psi-mi:“MI:2364”(proximity)	0.740
CWF19L2	TRIM37	psi-mi:“MI:0915”(physical association)	0.720
TRIM37	CWF19L2	psi-mi:“MI:0915”(physical association)	0.720
TRIM37	ZNF417	psi-mi:“MI:0915”(physical association)	0.670
TRIM37	MCRS1	psi-mi:“MI:0915”(physical association)	0.670
MCRS1	TRIM37	psi-mi:“MI:0915”(physical association)	0.670
TRIM37	COPB1	psi-mi:“MI:0915”(physical association)	0.670
TRIM37	SSX2IP	psi-mi:“MI:0915”(physical association)	0.660
PRC1	TRIM37	psi-mi:“MI:0915”(physical association)	0.630
	TRIM37	psi-mi:“MI:0915”(physical association)	0.560
TRIM37	FAM107A	psi-mi:“MI:0915”(physical association)	0.560
TRIM37	DDX6	psi-mi:“MI:0915”(physical association)	0.560
RPL9	TRIM37	psi-mi:“MI:0915”(physical association)	0.560
TRIM37	UBASH3A	psi-mi:“MI:0915”(physical association)	0.560
TRIM37	FAM161A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (742): TRIM37 (Two-hybrid), TRIM37 (Two-hybrid), RPL9 (Two-hybrid), MCRS1 (Two-hybrid), KAT5 (Two-hybrid), FAM107A (Two-hybrid), FAM50B (Two-hybrid), RASD1 (Two-hybrid), UBASH3A (Two-hybrid), KIF9 (Two-hybrid), SCNM1 (Two-hybrid), ZNF329 (Two-hybrid), FAM161A (Two-hybrid), SSX2IP (Two-hybrid), CWF19L2 (Two-hybrid)

ESM2 similar proteins: A0A2R6W1B1, A0FKI7, A2XC52, A2XTW9, A2Y0Q2, B8AMA8, B8B8I3, F4I9G2, O94972, P07106, P20067, P41135, P85828, Q5EAE9, Q5EAH9, Q5R7V3, Q5T8D3, Q5XEM9, Q5XG73, Q5XI67, Q6EPZ2, Q6GPE9, Q6IE24, Q6PCX9, Q70EL1, Q75IR6, Q76N89, Q7XUW3, Q84TV4, Q86UB2, Q8BJL1, Q8BL06, Q8CBX9, Q8H383, Q8H8C6, Q8K3A6, Q8K4P8, Q8LA16, Q8TB52, Q96S38

Diamond homologs: O94972, Q6PCX9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM37	ubiquitination
TRIM37	“down-regulates quantity by destabilization”	TRIM37	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	55
Uncertain significance	224
Likely benign	417
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323711	NM_015294.6(TRIM37):c.447del (p.Lys149fs)	Pathogenic
1458943	NC_000017.10:g.(?57119154)(57119279_?)del	Pathogenic
1705426	NM_015294.6(TRIM37):c.137_138del (p.Glu46fs)	Pathogenic
2026515	NM_015294.6(TRIM37):c.1723dup (p.Met575fs)	Pathogenic
2114437	NM_015294.6(TRIM37):c.1829del (p.Ser610fs)	Pathogenic
2426128	NC_000017.10:g.(?57119154)(57148328_?)del	Pathogenic
2679248	NM_015294.6(TRIM37):c.1999C>T (p.Arg667Ter)	Pathogenic
2679252	NM_015294.6(TRIM37):c.2437_2438insAT (p.Leu813fs)	Pathogenic
2695468	NM_015294.6(TRIM37):c.1207dup (p.Val403fs)	Pathogenic
2698047	NM_015294.6(TRIM37):c.1345A>T (p.Lys449Ter)	Pathogenic
2708178	NM_015294.6(TRIM37):c.537dup (p.Arg180fs)	Pathogenic
2726637	NM_015294.6(TRIM37):c.2029dup (p.Arg677fs)	Pathogenic
2757784	NM_015294.6(TRIM37):c.1768dup (p.Tyr590fs)	Pathogenic
2760722	NM_015294.6(TRIM37):c.827dup (p.Tyr276Ter)	Pathogenic
2763483	NM_015294.6(TRIM37):c.413_417dup (p.Val140fs)	Pathogenic
2829454	NM_015294.6(TRIM37):c.1527T>A (p.Tyr509Ter)	Pathogenic
2839946	NM_015294.6(TRIM37):c.450del (p.Arg151fs)	Pathogenic
2843500	NM_015294.6(TRIM37):c.468del (p.Glu156fs)	Pathogenic
2845486	NM_015294.6(TRIM37):c.2372_2381del (p.Gln791fs)	Pathogenic
2858318	NM_015294.6(TRIM37):c.2671G>T (p.Gly891Ter)	Pathogenic
2860850	NM_015294.6(TRIM37):c.351T>A (p.Cys117Ter)	Pathogenic
2883873	NM_015294.6(TRIM37):c.1960C>T (p.Arg654Ter)	Pathogenic
2893407	NM_015294.6(TRIM37):c.2652dup (p.Gln885fs)	Pathogenic
2904915	NM_015294.6(TRIM37):c.2323C>T (p.Arg775Ter)	Pathogenic
2905363	NM_015294.6(TRIM37):c.1336C>T (p.Arg446Ter)	Pathogenic
2910435	NM_015294.6(TRIM37):c.2461dup (p.Ile821fs)	Pathogenic
2959944	NM_015294.6(TRIM37):c.1579G>T (p.Glu527Ter)	Pathogenic
3001301	NM_015294.6(TRIM37):c.2274dup (p.Asn759Ter)	Pathogenic
3006762	NM_015294.6(TRIM37):c.2143dup (p.Ser715fs)	Pathogenic
3014315	NM_015294.6(TRIM37):c.2431C>T (p.Arg811Ter)	Pathogenic

SpliceAI

5052 predictions. Top by Δscore:

Variant	Effect	Δscore
17:58987907:T:TA	donor_gain	1.0000
17:58996973:T:TA	donor_gain	1.0000
17:59012324:TTA:T	donor_loss	1.0000
17:59012324:TTAC:T	donor_gain	1.0000
17:59012325:TACC:T	donor_loss	1.0000
17:59012326:A:AC	donor_gain	1.0000
17:59012327:C:CC	donor_gain	1.0000
17:59012327:C:CG	donor_loss	1.0000
17:59012327:CCTT:C	donor_gain	1.0000
17:59012447:C:T	acceptor_gain	1.0000
17:59012449:C:CT	acceptor_gain	1.0000
17:59015629:T:TA	donor_gain	1.0000
17:59041809:TTA:T	donor_loss	1.0000
17:59041811:A:C	donor_loss	1.0000
17:59041894:CAGAC:C	acceptor_gain	1.0000
17:59041895:AGAC:A	acceptor_gain	1.0000
17:59041896:GAC:G	acceptor_gain	1.0000
17:59041897:AC:A	acceptor_gain	1.0000
17:59041898:CC:C	acceptor_gain	1.0000
17:59041899:C:CA	acceptor_loss	1.0000
17:59041899:C:CC	acceptor_gain	1.0000
17:59041905:A:AC	acceptor_gain	1.0000
17:59047674:GAAAC:G	donor_loss	1.0000
17:59047676:AACTC:A	donor_loss	1.0000
17:59047677:ACTCA:A	donor_loss	1.0000
17:59047678:CTC:C	donor_loss	1.0000
17:59047679:T:TG	donor_loss	1.0000
17:59047680:C:CC	donor_loss	1.0000
17:59047681:A:AC	donor_gain	1.0000
17:59047682:C:CG	donor_gain	1.0000

AlphaMissense

6377 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:59051290:C:G	R413P	1.000
17:59051317:C:G	R404P	1.000
17:59051318:G:T	R404S	1.000
17:59056878:A:G	L399S	1.000
17:59056909:A:C	Y389D	1.000
17:59056923:A:G	L384P	1.000
17:59056923:A:T	L384H	1.000
17:59056937:G:C	F379L	1.000
17:59056937:G:T	F379L	1.000
17:59056939:A:G	F379L	1.000
17:59056940:A:C	F378L	1.000
17:59056940:A:T	F378L	1.000
17:59056941:A:C	F378C	1.000
17:59056941:A:G	F378S	1.000
17:59056942:A:G	F378L	1.000
17:59056943:T:A	R377S	1.000
17:59056943:T:G	R377S	1.000
17:59056944:C:A	R377I	1.000
17:59056944:C:G	R377T	1.000
17:59056946:A:C	N376K	1.000
17:59056946:A:T	N376K	1.000
17:59056950:T:C	Y375C	1.000
17:59056951:A:C	Y375D	1.000
17:59056951:A:G	Y375H	1.000
17:59056953:C:A	G374V	1.000
17:59056953:C:T	G374D	1.000
17:59056954:C:A	G374C	1.000
17:59056954:C:G	G374R	1.000
17:59056954:C:T	G374S	1.000
17:59056955:C:A	W373C	1.000

dbSNP variants (sampled 300 via entrez): RS1000002406 (17:58973363 G>C), RS1000009050 (17:59020120 A>G), RS1000064477 (17:59018995 G>A,T), RS1000077758 (17:59070018 G>A,C), RS1000093042 (17:59040995 G>A), RS1000105362 (17:59104985 A>T), RS1000109107 (17:58974925 C>T), RS1000109205 (17:58998292 C>T), RS1000134279 (17:59044686 T>C), RS1000149926 (17:59061712 T>A), RS1000163347 (17:58991562 A>G), RS1000187899 (17:59048887 G>A,T), RS1000211984 (17:58988886 A>T), RS1000226176 (17:58988420 C>A), RS1000229520 (17:59033221 C>T)

Disease associations

OMIM: gene MIM:605073 | disease phenotypes: MIM:253250

GenCC curated gene-disease

Disease	Classification	Inheritance
mulibrey nanism	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mulibrey nanism	Definitive	AR

Mondo (1): mulibrey nanism (MONDO:0009664)

Orphanet (1): Mulibrey nanism (Orphanet:2576)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000171	Microglossia
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000580	Pigmentary retinopathy
HP:0000612	Iris coloboma
HP:0000668	Hypodontia
HP:0000678	Dental crowding
HP:0000689	Dental malocclusion
HP:0000935	Thickened cortex of long bones
HP:0000954	Single transverse palmar crease
HP:0001052	Nevus flammeus
HP:0001131	Corneal dystrophy
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001315	Reduced tendon reflexes
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001541	Ascites
HP:0001620	Abnormally high-pitched voice
HP:0001621	Weak voice
HP:0001635	Congestive heart failure
HP:0001640	Cardiomegaly

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002023_1	Testicular germ cell tumor	4.000000e-13
GCST002774_29	Cognitive function	3.000000e-07
GCST006269_522	General cognitive ability	2.000000e-14
GCST010002_126	Refractive error	7.000000e-42
GCST90002396_668	Mean reticulocyte volume	3.000000e-17
GCST90002397_580	Mean spheric corpuscular volume	2.000000e-19

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D050336	Mulibrey Nanism	C05.116.099.343.796; C16.320.240.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Formaldehyde	decreases expression	1
Manganese	decreases expression, increases abundance	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 finite cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TU15	HAP1 TRIM37 (-) 1	Cancer cell line	Male
CVCL_TU16	HAP1 TRIM37 (-) 2	Cancer cell line	Male
CVCL_X808	AG02122	Finite cell line	Female
CVCL_X809	AG02505	Finite cell line	Female
CVCL_X810	AG02506	Finite cell line	Female

Clinical trials (associated diseases)

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