TRIM33

tripartite motif containing 33, the group of Tripartite motif family|Ring finger proteins|Bromodomain containing|PHD finger proteins

Basic information

Region (hg38): 1:114392790-114511203

Links

ENSG00000197323

∙ NCBI:51592 ∙ OMIM:605769 ∙ HGNC:16290 ∙ Uniprot:Q9UPN9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIM33 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIM33 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					5 clinvar	5
missense			24 clinvar		4 clinvar	28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	24	0	9

Variants in TRIM33

This is a list of pathogenic ClinVar variants found in the TRIM33 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
1-114397674-C-T	not specified	Uncertain significance (May 08, 2024)	3328706
1-114397685-C-T	not specified	Uncertain significance (Mar 08, 2024)	3182386
1-114397757-A-T	not specified	Uncertain significance (May 01, 2024)	3328703
1-114399512-T-C	not specified	Uncertain significance (Sep 28, 2022)	2311134
1-114399609-T-C	not specified	Uncertain significance (Feb 27, 2023)	2490030
1-114401390-G-A	not specified	Uncertain significance (Apr 15, 2024)	3328705
1-114402772-G-A		Benign (Jul 31, 2018)	782385
1-114405687-A-G		Benign (Apr 20, 2018)	775577
1-114405701-C-G	Ovarian cancer	Benign (Jan 01, 2022)	2445282
1-114406979-G-C	not specified	Uncertain significance (Jul 19, 2022)	2302347
1-114407017-G-C	not specified	Uncertain significance (Mar 14, 2023)	2495920
1-114421576-T-C	not specified	Uncertain significance (Feb 12, 2024)	3182382
1-114421583-G-C		Benign (Mar 29, 2018)	738608
1-114421587-T-G	not specified	Uncertain significance (Jan 23, 2024)	3182381
1-114421603-C-T	not specified	Uncertain significance (Oct 02, 2023)	3182380
1-114421610-G-C		Benign (Feb 13, 2018)	786854
1-114421612-G-T	not specified	Uncertain significance (Oct 10, 2023)	3182379
1-114425493-G-GACA	Developmental dysplasia of the hip	Likely pathogenic (-)	3063595
1-114425560-A-C	not specified	Uncertain significance (Apr 22, 2022)	2284900
1-114427840-C-T	Ovarian cancer	Benign (Jan 01, 2022)	2445278
1-114427894-T-G	not specified	Uncertain significance (Apr 05, 2023)	2524190
1-114430807-T-C		Benign (Nov 14, 2019)	1278118
1-114463420-T-C	not specified	Uncertain significance (May 28, 2024)	3328707
1-114464292-C-A	not specified	Uncertain significance (May 26, 2022)	2291265
1-114510574-C-A	not specified	Uncertain significance (Oct 17, 2023)	3182388

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIM33	protein_coding	protein_coding	ENST00000358465	20	118383

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.11e-8	125721	0	3	125724	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.49	259	557	0.465	0.0000280	7351
Missense in Polyphen		31	160.58	0.19306		2120
Synonymous	-0.810	211	197	1.07	0.0000100	2158
Loss of Function	6.74	1	54.9	0.0182	0.00000286	653

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000664	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF- beta/BMP signaling cascade). {ECO:0000250, ECO:0000269|PubMed:10022127, ECO:0000269|PubMed:15820681, ECO:0000269|PubMed:16751102, ECO:0000269|PubMed:19135894}.;
Disease: DISEASE: Note=A chromosomal aberration involving TRIM33 is found in papillary thyroid carcinomas (PTCs). Translocation t(1;10)(p13;q11) with RET. The translocation generates the TRIM33/RET (PTC7) oncogene. {ECO:0000269|PubMed:10439047}.;
Pathway: TGF-Ncore;Ectoderm Differentiation;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Downregulation of SMAD2/3:SMAD4 transcriptional activity;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members (Consensus)

Recessive Scores

pRec: 0.151

Intolerance Scores

loftool: 0.0280
rvis_EVS: -0.64
rvis_percentile_EVS: 16.53

Haploinsufficiency Scores

pHI: 0.868
hipred: Y
hipred_score: 0.739
ghis: 0.647

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Trim33
Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; immune system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype;

Zebrafish Information Network

Gene name: trim33
Affected structure: neutrophil
Phenotype tag: abnormal
Phenotype quality: aggregated

Gene ontology

Biological process: negative regulation of transcription by RNA polymerase II;protein ubiquitination;regulation of transforming growth factor beta receptor signaling pathway;negative regulation of BMP signaling pathway;negative regulation of transcription, DNA-templated
Cellular component: nucleus;nucleoplasm
Molecular function: DNA binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;co-SMAD binding;R-SMAD binding