TRIM49

Summary

TRIM49 (tripartite motif containing 49, HGNC:13431) is a protein-coding gene on chromosome 11q14.3, encoding Tripartite motif-containing protein 49 (P0CI25).

The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This gene has been found to be preferentially expressed in testis. Related pseudogenes and gene duplicates have also been identified on chromosome 11.

Source: NCBI Gene 57093 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_020358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13431
Approved symbol	TRIM49
Name	tripartite motif containing 49
Location	11q14.3
Locus type	gene with protein product
Status	Approved
Aliases	TRIM49A
Ensembl gene	ENSG00000168930
Ensembl biotype	protein_coding
OMIM	606124
Entrez	57093

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000329758, ENST00000532501

RefSeq mRNA: 1 — MANE Select: NM_020358 NM_020358

CCDS: CCDS8287

Canonical transcript exons

ENST00000329758 — 8 exons

Exon	Start	End
ENSE00002448819	89797655	89798629
ENSE00002454974	89807099	89807284
ENSE00002475671	89800966	89800988
ENSE00002478160	89808437	89808575
ENSE00002492944	89804059	89804473
ENSE00002508333	89799716	89799813
ENSE00002508616	89803698	89803793
ENSE00002527452	89801702	89801932

Expression profiles

Bgee: expression breadth broad, 12 present calls, max score 83.52.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.52	gold quality
lower esophagus mucosa	UBERON:0035834	38.29	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.87	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
mucosa of stomach	UBERON:0001199	32.89	gold quality
muscle tissue	UBERON:0002385	32.43	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
prefrontal cortex	UBERON:0000451	31.49	gold quality
testis	UBERON:0000473	30.73	gold quality
right testis	UBERON:0004534	29.94	silver quality
monocyte	CL:0000576	29.91	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
leukocyte	CL:0000738	29.70	gold quality
superior frontal gyrus	UBERON:0002661	29.60	gold quality
liver	UBERON:0002107	29.04	gold quality
rectum	UBERON:0001052	29.01	silver quality
smooth muscle tissue	UBERON:0001135	28.69	silver quality
lymph node	UBERON:0000029	28.67	gold quality
left testis	UBERON:0004533	28.26	silver quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.92	gold quality
islet of Langerhans	UBERON:0000006	27.64	gold quality
tonsil	UBERON:0002372	27.05	gold quality
calcaneal tendon	UBERON:0003701	26.90	gold quality
blood	UBERON:0000178	26.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	228.81
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting TRIM49, 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-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-5190	99.15	67.76	1234

Literature-anchored findings (GeneRIF, showing 1)

• Expressed and purified human TRIM49 protein, and investigated the role of the SPRY and RING domains of human TRIM49 protein in E3 ubiquitin ligase activity. (PMID:29107100)

Cross-species orthologs

0 orthologs

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 49 — P0CI25 (reviewed: P0CI25)

Alternative names: RING finger protein 18, Testis-specific RING-finger protein

All UniProt accessions (2): P0CI25, E9PK69

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Preferentially expressed in testis.

Similarity. Belongs to the TRIM/RBCC family.

RefSeq proteins (1): NP_065091* (*=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
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF15227

UniProt features (10 total): binding site 4, zinc finger region 2, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CI25-F1	85.51	0.62

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): 93; 96; 115; 121

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOZGIT_ESR1_TARGETS_DN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, BLALOCK_ALZHEIMERS_DISEASE_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GOMF_KINASE_BINDING, MIR9983_3P, MIR506_3P, MIR124_3P, MIR655_3P, MIR374C_5P, MIR129_5P, MIR1252_3P

GO Biological Process (2): regulation of gene expression (GO:0010468), innate immune response (GO:0045087)

GO Molecular Function (5): zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
regulation of macromolecule biosynthetic process	1
immune response	1
defense response to symbiont	1
transition metal ion binding	1
kinase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM49	BBOX1	O75936	709
TRIM49	NAALAD2	Q9Y3Q0	538
TRIM49	MBD3L3	A6NE82	513
TRIM49	PRAMEF13	Q5VWM6	479
TRIM49	PRAMEF11	O60813	477
TRIM49	KHDC1L	Q5JSQ8	475
TRIM49	PRAMEF2	O60811	474
TRIM49	PRAMEF25	A6NGN4	447
TRIM49	A0A096LNW4	A0A096LNW4	419
TRIM49	TRAT1	Q6PIZ9	417
TRIM49	PRAMEF15	P0DUQ1	417
TRIM49	PRAMEF1	O95521	392
TRIM49	FOLH1	Q04609	379
TRIM49	LEUTX	A8MZ59	376
TRIM49	KHDC1	Q4VXA5	376

IntAct

27 interactions, top by confidence:

A	B	Type	Score
TRIM49	CKS1B	psi-mi:“MI:0914”(association)	0.740
TRIM49	MINDY3	psi-mi:“MI:0915”(physical association)	0.740
TRIM49	CKS1B	psi-mi:“MI:0915”(physical association)	0.740
TRIM49	POM121	psi-mi:“MI:0915”(physical association)	0.560
TRIM49		psi-mi:“MI:0915”(physical association)	0.560
TRIM49	HTT	psi-mi:“MI:0915”(physical association)	0.560
HSP90AB1	TRIM49	psi-mi:“MI:0915”(physical association)	0.400
TRIM49	MINDY3	psi-mi:“MI:0915”(physical association)	0.000
CKS1B	TRIM49	psi-mi:“MI:0915”(physical association)	0.000
POM121	TRIM49	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): BLM (Reconstituted Complex), CUL1 (Affinity Capture-MS), SKP2 (Affinity Capture-MS), CKS1B (Affinity Capture-MS), CKS1B (Affinity Capture-MS), SKP2 (Affinity Capture-MS), FAM188A (Affinity Capture-MS), TRIM49 (Reconstituted Complex), TRIM49 (Reconstituted Complex), LGALS3 (Affinity Capture-Western), TRIM49 (Two-hybrid), CKS1B (Two-hybrid), POM121 (Two-hybrid), CKS1B (Affinity Capture-MS), FAM188A (Affinity Capture-MS)

ESM2 similar proteins: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, C9J1S8, I1YAP6, K7N6K2, P0CI25, P0CI26, P15533, Q0PF16, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3ZEE5, Q587N6, Q587N7, Q5BN31, Q5C8T6, Q5C8T8, Q5C8U1, Q5C8U3, Q5C8U4, Q5D7H7, Q5D7H8, Q5D7I0, Q5D7I1, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7I6, Q5D7I9, Q5D7J0

Diamond homologs: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, B0BLU1, C9J1S8, I1YAP6, O00478, O00481, O15344, O75677, O75678, O75679, O76064, P0CI25, P0CI26, P18892, P19474, P62603, P86448, P86449, Q13410, Q2HJ46, Q3C1V9, Q3TL54, Q4KLN8, Q5EBN2, Q5PQN2, Q5R4I2, Q5R996, Q61510, Q62556, Q6INS5, Q6MFY8, Q6UX41, Q6UXE8, Q6ZWI9, Q7T308

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM49	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

758 predictions. Top by Δscore:

Variant	Effect	Δscore
11:89798625:ATGCA:A	acceptor_gain	1.0000
11:89798626:TGCA:T	acceptor_gain	1.0000
11:89798627:GCA:G	acceptor_gain	1.0000
11:89798628:CA:C	acceptor_gain	1.0000
11:89798628:CAC:C	acceptor_gain	1.0000
11:89798629:ACTGC:A	acceptor_loss	1.0000
11:89798630:C:CA	acceptor_loss	1.0000
11:89798630:C:CC	acceptor_gain	1.0000
11:89798633:C:CT	acceptor_gain	1.0000
11:89798634:A:T	acceptor_gain	1.0000
11:89799711:CTTA:C	donor_loss	1.0000
11:89799712:TTA:T	donor_loss	1.0000
11:89799713:TAC:T	donor_loss	1.0000
11:89799714:A:AC	donor_gain	1.0000
11:89799714:AC:A	donor_gain	1.0000
11:89799714:ACCT:A	donor_gain	1.0000
11:89799715:C:CT	donor_gain	1.0000
11:89799715:CC:C	donor_gain	1.0000
11:89799715:CCT:C	donor_gain	1.0000
11:89799715:CCTC:C	donor_gain	1.0000
11:89799715:CCTCG:C	donor_gain	1.0000
11:89799809:CACTC:C	acceptor_gain	1.0000
11:89799811:CTC:C	acceptor_gain	1.0000
11:89799812:TC:T	acceptor_gain	1.0000
11:89799813:CC:C	acceptor_gain	1.0000
11:89799814:C:CC	acceptor_gain	1.0000
11:89799815:T:A	acceptor_loss	1.0000
11:89800962:TCA:T	donor_loss	1.0000
11:89800963:CA:C	donor_loss	1.0000
11:89800964:ACC:A	donor_loss	1.0000

AlphaMissense

3045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:89798223:A:C	F422L	0.961
11:89798223:A:T	F422L	0.961
11:89798225:A:G	F422L	0.961
11:89799720:G:C	F285L	0.951
11:89799720:G:T	F285L	0.951
11:89799722:A:G	F285L	0.951
11:89804161:G:C	F103L	0.946
11:89804161:G:T	F103L	0.946
11:89804163:A:G	F103L	0.946
11:89798432:A:G	W353R	0.935
11:89798432:A:T	W353R	0.935
11:89804060:C:G	R137P	0.935
11:89798462:A:G	W343R	0.933
11:89798462:A:T	W343R	0.933
11:89798253:G:C	F412L	0.932
11:89798253:G:T	F412L	0.932
11:89798255:A:G	F412L	0.932
11:89804368:A:C	F34L	0.920
11:89804368:A:T	F34L	0.920
11:89804370:A:G	F34L	0.920
11:89803703:A:G	W168R	0.918
11:89803703:A:T	W168R	0.918
11:89798226:G:C	S421R	0.913
11:89798226:G:T	S421R	0.913
11:89798228:T:G	S421R	0.913
11:89798355:A:C	F378L	0.911
11:89798355:A:T	F378L	0.911
11:89798357:A:G	F378L	0.911
11:89798460:C:A	W343C	0.911
11:89798460:C:G	W343C	0.911

dbSNP variants (sampled 300 via entrez): RS1000008425 (11:89800360 C>T), RS1000116712 (11:89781172 A>G), RS1000466574 (11:89799042 A>C), RS1000571334 (11:89785759 T>C), RS1000634994 (11:89766004 T>A), RS1001069233 (11:89802858 G>A), RS1001119570 (11:89800977 G>A,T), RS1001123620 (11:89784923 A>C), RS1001183457 (11:89800592 A>C,G), RS1001350590 (11:89783434 T>C,G), RS1001353369 (11:89802317 CATT>C), RS1002175993 (11:89803781 G>A,T), RS1002399798 (11:89786759 G>A,C), RS1002463242 (11:89767185 C>T), RS1002755400 (11:89787192 G>C)

Disease associations

OMIM: gene MIM:606124 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001692_8	Response to taxane treatment (docetaxel)	8.000000e-06
GCST007998_24	Intraocular pressure	3.000000e-07
GCST012020_222	Serum metabolite levels	6.000000e-20

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases methylation	2
TAK-243	increases sumoylation	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
EPZ004777	decreases expression	1
Cadmium	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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