TRIM71

Summary

TRIM71 (tripartite motif containing 71, HGNC:32669) is a protein-coding gene on chromosome 3p22.3, encoding E3 ubiquitin-protein ligase TRIM71 (Q2Q1W2). E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance.

The protein encoded by this gene is an E3 ubiquitin-protein ligase that binds with miRNAs and maintains the growth and upkeep of embryonic stem cells. This gene also is involved in the G1-S phase transition of the cell cycle.

Source: NCBI Gene 131405 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hydrocephalus, congenital communicating, 1 (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 174 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_001039111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32669
Approved symbol	TRIM71
Name	tripartite motif containing 71
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Aliases	LIN41, LIN-41
Ensembl gene	ENSG00000206557
Ensembl biotype	protein_coding
OMIM	618570
Entrez	131405

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000383763, ENST00000918245, ENST00000918246

RefSeq mRNA: 1 — MANE Select: NM_001039111 NM_001039111

CCDS: CCDS43060

Canonical transcript exons

ENST00000383763 — 4 exons

Exon	Start	End
ENSE00001498538	32890360	32897824
ENSE00001498539	32885934	32886068
ENSE00001498540	32873818	32873985
ENSE00001538095	32817997	32818932

Expression profiles

Bgee: expression breadth broad, 69 present calls, max score 90.78.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9243 / max 36.0727, expressed in 184 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35908	0.3011	129
35907	0.2252	91
35909	0.1912	80
35910	0.1496	82
35906	0.0572	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	90.78	gold quality
oocyte	CL:0000023	87.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.38	gold quality
buccal mucosa cell	CL:0002336	77.92	gold quality
adult organism	UBERON:0007023	72.61	gold quality
kidney epithelium	UBERON:0004819	72.57	gold quality
germinal epithelium of ovary	UBERON:0001304	71.25	silver quality
testis	UBERON:0000473	66.54	gold quality
oviduct epithelium	UBERON:0004804	64.15	gold quality
cortical plate	UBERON:0005343	63.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	63.66	silver quality
right testis	UBERON:0004534	63.10	gold quality
left testis	UBERON:0004533	62.23	gold quality
ileal mucosa	UBERON:0000331	60.77	gold quality
placenta	UBERON:0001987	60.29	gold quality
tibialis anterior	UBERON:0001385	59.15	silver quality
kidney	UBERON:0002113	57.37	gold quality
adult mammalian kidney	UBERON:0000082	56.64	gold quality
vena cava	UBERON:0004087	55.53	gold quality
upper leg skin	UBERON:0004262	55.27	silver quality
ganglionic eminence	UBERON:0004023	55.07	silver quality
pancreatic ductal cell	CL:0002079	54.46	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	53.98	gold quality
postcentral gyrus	UBERON:0002581	53.74	gold quality
nucleus accumbens	UBERON:0001882	53.65	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
lung	UBERON:0002048	53.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	91.92
E-ANND-3	yes	5.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

285 targeting TRIM71, 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-4262	100.00	73.26	3931
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 13)

• Repression of human TRIM71 and the zebrafish lin-41 ortholog was abolished when predicted let-7 target sites were mutated. Regulation of TRIM71 expression by let-7 seems to have been evolutionarily conserved. (PMID:17890240)
• Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation (PMID:22735451)
• The stem cell E3-ligase Lin-41 promotes liver cancer progression through inhibition of microRNA-mediated gene silencing. (PMID:23097274)
• poiopi poiopi i90iy9oyu8 (PMID:23892092)
• Consistent with the let-7 microRNA stimulatory role of TRIM71 via Lin28B polyubiquitination. (PMID:24602972)
• Studies indicate most-studied TRIpartite Motif (TRIM)-NHL proteins TRIM2, TRIM3, TRIM32 and TRIM71, and their mutations have been linked to diseases. (PMID:26514622)
• TRIM71 acts through post-transcriptional repression of Lin28B and subsequent modulation of let-7-HMGA2 signaling during tumorigenesis to potentially function as a tumor suppressor. (PMID:27821801)
• TRIM71 mutations implicated in etiogenesis of human congenital hydrocephalus impair target silencing (PMID:31371437)
• Ubiquitin ligase TRIM71 suppresses ovarian tumorigenesis by degrading mutant p53. (PMID:31570706)
• TRIM71-mediated target recognition and repression mechanisms uncovers a role for this stem cell-specific factor and oncogene in non-canonical Nonsense-mediated Decay (NMD), revealing the existence of a novel mRNA surveillance mechanism which has been termed here the TRIM71/NMD axis. (PMID:31732746)
• TRIM71 binds to IMP1 and is capable of positive and negative regulation of target RNAs. (PMID:32816599)
• TRIM7 Restricts Coxsackievirus and Norovirus Infection by Detecting the C-Terminal Glutamine Generated by 3C Protease Processing. (PMID:35893676)
• HDLBP Promotes Hepatocellular Carcinoma Proliferation and Sorafenib Resistance by Suppressing Trim71-dependent RAF1 Degradation. (PMID:36244648)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim71	ENSDARG00000075593
mus_musculus	Trim71	ENSMUSG00000079259

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

E3 ubiquitin-protein ligase TRIM71 — Q2Q1W2 (reviewed: Q2Q1W2)

Alternative names: Protein lin-41 homolog, RING-type E3 ubiquitin transferase TRIM71, Tripartite motif-containing protein 71

All UniProt accessions (1): Q2Q1W2

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance. Binds to miRNAs and associates with AGO2, participating in post-transcriptional repression of transcripts such as CDKN1A. In addition, participates in post-transcriptional mRNA repression in a miRNA independent mechanism. Facilitates the G1-S transition to promote rapid embryonic stem cell self-renewal by repressing CDKN1A expression. Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development: positively regulates FGF signaling by controlling the stability of SHCBP1. Specific regulator of miRNA biogenesis. Binds to miRNA MIR29A hairpin and postranscriptionally modulates MIR29A levels, which indirectly regulates TET proteins expression.

Subunit / interactions. Interacts (via NHL repeats) with AGO2; the interaction increases in presence of RNA. Interacts with HSP90AA1. Interacts (via NHL repeats) with MOV10, PABPC1, PUM1, PUM2, STAU2, XRN1 and XRN2 in an RNA-dependent manner. Interacts with SHCBP1; leading to enhance its stability.

Subcellular location. Cytoplasm. P-body.

Tissue specificity. Specifically expressed in testis.

Post-translational modifications. Autoubiquitinated.

Disease relevance. Hydrocephalus, congenital, 4 (HYC4) [MIM:618667] An autosomal dominant form of congenital hydrocephalus, a disease characterized by in utero onset of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. HYC4 occurs in the absence of obstruction to cerebrospinal fluid flow between the ventricles (communicating hydrocephalus). Affected individuals have neurodevelopmental delay and epilepsy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The NHL domain, containing the 6 NHL repeats, is necessary and sufficient to target RNA but not to repress mRNA. The minimal region needed to execute repression consists of the coiled coil domain and the Filamin repeat. The RING-type domain is dispensable for mRNA repression.

Induction. Negatively regulated by the microRNA (miRNA) let-7 which causes degradation of the mRNA encoding this protein. This requires a let-7 complementary site (LCS) in the 3’-UTR of the mRNA encoding this protein. Down-regulated by retinoic acid in Tera-2 cells.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

RefSeq proteins (1): NP_001034200* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001258	NHL_repeat	Repeat
IPR001298	Filamin/ABP280_rpt	Repeat
IPR001841	Znf_RING	Domain
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR017868	Filamin/ABP280_rpt-like	Repeat
IPR017907	Znf_RING_CS	Conserved_site
IPR018957	Znf_C3HC4_RING-type	Domain
IPR050952	TRIM-NHL_E3_ligases	Family

Pfam: PF00097, PF00630, PF00643, PF01436

UniProt features (66 total): strand 29, repeat 7, helix 6, compositionally biased region 4, binding site 4, mutagenesis site 4, zinc finger region 3, region of interest 2, sequence variant 2, initiator methionine 1, chain 1, coiled-coil region 1, modified residue 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7QRX	X-RAY DIFFRACTION	2.2
9JUR	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2Q1W2-F1	80.50	0.46

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): 278; 281; 301; 306

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (4):

Position	Phenotype
647	strongly decreases repression on mrna.
675	abolishes repression on mrna. abolishes interaction with ago2, pabpc1 and pum2. increases interaction with hsp90aa1.
702	decreases repression on mrna. decreases interaction with hsp90aa1. abolishes interaction with pabpc1 and pum2. increases
751	decreases repression on mrna. abolishes interaction with ago2, hsp90aa1, pabpc1 and pum2.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 181 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_STEM_CELL_PROLIFERATION, GOBP_TRANSLATION

GO Biological Process (19): G1/S transition of mitotic cell cycle (GO:0000082), protein polyubiquitination (GO:0000209), neural tube closure (GO:0001843), fibroblast growth factor receptor signaling pathway (GO:0008543), post-transcriptional regulation of gene expression (GO:0010608), negative regulation of translation (GO:0017148), neural tube development (GO:0021915), miRNA processing (GO:0035196), miRNA-mediated gene silencing by inhibition of translation (GO:0035278), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein autoubiquitination (GO:0051865), 3’-UTR-mediated mRNA destabilization (GO:0061158), stem cell proliferation (GO:0072089), regulation of neural precursor cell proliferation (GO:2000177), positive regulation of miRNA-mediated gene silencing (GO:2000637), protein ubiquitination (GO:0016567), regulatory ncRNA-mediated gene silencing (GO:0031047), regulation of protein metabolic process (GO:0051246), regulation of miRNA-mediated gene silencing (GO:0060964)

GO Molecular Function (9): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), translation repressor activity (GO:0030371), miRNA binding (GO:0035198), ubiquitin protein ligase activity (GO:0061630), RNA binding (GO:0003723), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (2): P-body (GO:0000932), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
miRNA-mediated post-transcriptional gene silencing	3
protein ubiquitination	2
negative regulation of gene expression	2
negative regulation of translation	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
primary neural tube formation	1
tube closure	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
regulation of gene expression	1
translation	1
regulation of translation	1
negative regulation of protein metabolic process	1
nervous system development	1
tube development	1
chordate embryonic development	1
epithelium development	1
regulatory ncRNA processing	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
mRNA destabilization	1
cell population proliferation	1
stem cell division	1
regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of miRNA-mediated gene silencing	1
positive regulation of post-transcriptional gene silencing by RNA	1
protein modification by small protein conjugation	1
protein metabolic process	1
regulation of macromolecule metabolic process	1
regulation of primary metabolic process	1
regulation of post-transcriptional gene silencing by regulatory ncRNA	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
translation regulator activity	1
regulatory RNA binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1

Protein interactions and networks

STRING

914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM71	AGO2	Q9UKV8	874
TRIM71	CAPN3	P20807	844
TRIM71	BBOX1	O75936	820
TRIM71	ZNF362	Q5T0B9	724
TRIM71	LIN28A	Q9H9Z2	679
TRIM71	TRAT1	Q6PIZ9	604
TRIM71	MEX3D	Q86XN8	602
TRIM71	XRN1	Q8IZH2	496
TRIM71	DICER1	Q9UPY3	488
TRIM71	CPEB1	Q9BZB8	478
TRIM71	LIN28B	Q6ZN17	475
TRIM71	EGR1	P18146	465
TRIM71	HSP90AA1	P07900	463
TRIM71	UBE2N	P61088	459
TRIM71	HSP90AB1	P08238	459

IntAct

73 interactions, top by confidence:

A	B	Type	Score
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
THAP2	OGT	psi-mi:“MI:0914”(association)	0.530
E4F1	ZBTB24	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
THAP3	CASC3	psi-mi:“MI:0914”(association)	0.530
H1-4	RRP8	psi-mi:“MI:0914”(association)	0.530
SYCE3	RER1	psi-mi:“MI:0914”(association)	0.530
H1-1	SURF6	psi-mi:“MI:0914”(association)	0.530
CXCR2	PSMD11	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
CDX1	ZNF724	psi-mi:“MI:0914”(association)	0.350
FGF8	ANKHD1	psi-mi:“MI:0914”(association)	0.350
RRS1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
SYCE3	TRIM24	psi-mi:“MI:0914”(association)	0.350
C6orf11	RRP8	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
CEP63	CIT	psi-mi:“MI:0914”(association)	0.350

BioGRID (114): TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS), TRIM71 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A4IF63, A4II46, A6QQZ7, A8KBF6, D2GXS7, D3ZQG6, D3ZVM4, E1BJS7, E7FAM5, F6QEU4, F7H9X2, O60733, O70277, O75382, P23727, P26450, P27986, P42694, P49754, P79987, P97570, P97819, Q15139, Q1LY10, Q1PRL4, Q1PSW8, Q28C55, Q2Q1W2, Q2T9K6, Q59H18, Q5GIG6, Q5R685, Q5RF15, Q5T2T1, Q5U2Y3, Q63787, Q7TQP6, Q8AVG0, Q8BVD5

Diamond homologs: D3ZHA0, D3ZVM4, E1BJS7, E7FAM5, F6QEU4, M9PH32, O08629, O75369, P13466, Q13263, Q14315, Q1PRL4, Q1PSW8, Q2Q1W2, Q62318, Q80X90, Q8VHX6, Q9VEN1, P21333, Q8BTM8, P34611, A4IF63, A5D7D1, D2GXS7, D3ZHV2, D3ZQG6, F7H9X2, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O76329, O88990, O97592, P05094, P05095, P11277, P11530

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM71	ubiquitination
TRIM71	“down-regulates quantity by destabilization”	LIN28B	polyubiquitination
TRIM71	“down-regulates quantity”	TP53	ubiquitination
SOX2/POU5F1	“up-regulates quantity by expression”	TRIM71	“transcriptional regulation”
SOX17/POU5F1	“up-regulates quantity by expression”	TRIM71	“transcriptional regulation”
PRKACA	“up-regulates quantity by stabilization”	TRIM71	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
rRNA processing in the nucleus and cytosol	5	14.6×	4e-04
Peptide chain elongation	6	13.8×	2e-04
Viral mRNA Translation	6	13.8×	2e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	13.7×	2e-04
rRNA processing	5	13.3×	7e-04
Selenocysteine synthesis	6	13.1×	2e-04
Eukaryotic Translation Termination	6	13.1×	2e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	6	12.8×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	7	21.0×	2e-05
cytoplasmic translation	7	17.1×	4e-05
negative regulation of translation	6	15.5×	3e-04
rRNA processing	7	13.0×	2e-04
translation	6	8.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	135
Likely benign	24
Benign	2

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
4076516	NM_001039111.3(TRIM71):c.1963C>T (p.Arg655Ter)	Pathogenic
4076517	NM_001039111.3(TRIM71):c.236_242dup (p.Ala82fs)	Pathogenic
694594	NM_001039111.3(TRIM71):c.1823G>A (p.Arg608His)	Pathogenic
694595	NM_001039111.3(TRIM71):c.2387G>A (p.Arg796His)	Pathogenic
3030058	NM_001039111.3(TRIM71):c.707A>G (p.His236Arg)	Likely pathogenic
684689	NM_001039111.3(TRIM71):c.1886G>A (p.Arg629His)	Likely pathogenic
996339	NM_001039111.3(TRIM71):c.224_240dup (p.Gly81fs)	Likely pathogenic

SpliceAI

1528 predictions. Top by Δscore:

Variant	Effect	Δscore
3:32818933:GTG:G	donor_loss	1.0000
3:32873812:CCCCA:C	acceptor_loss	1.0000
3:32873813:CCCA:C	acceptor_loss	1.0000
3:32873814:CCA:C	acceptor_loss	1.0000
3:32873815:CA:C	acceptor_loss	1.0000
3:32873816:A:AG	acceptor_gain	1.0000
3:32873816:AG:A	acceptor_gain	1.0000
3:32873816:AGGTG:A	acceptor_loss	1.0000
3:32873817:G:GA	acceptor_gain	1.0000
3:32873817:GG:G	acceptor_gain	1.0000
3:32873817:GGT:G	acceptor_gain	1.0000
3:32873817:GGTGC:G	acceptor_gain	1.0000
3:32873984:AGG:A	donor_loss	1.0000
3:32873986:G:C	donor_loss	1.0000
3:32873986:G:GG	donor_gain	1.0000
3:32885923:T:A	acceptor_gain	1.0000
3:32885929:TCCA:T	acceptor_loss	1.0000
3:32885930:CCAG:C	acceptor_loss	1.0000
3:32885931:CAG:C	acceptor_loss	1.0000
3:32885932:A:AG	acceptor_gain	1.0000
3:32885932:AGCT:A	acceptor_gain	1.0000
3:32885933:G:GA	acceptor_gain	1.0000
3:32885933:GC:G	acceptor_gain	1.0000
3:32885933:GCT:G	acceptor_gain	1.0000
3:32885933:GCTG:G	acceptor_gain	1.0000
3:32885933:GCTGA:G	acceptor_gain	1.0000
3:32886023:GCA:G	donor_gain	1.0000
3:32886050:GT:G	donor_gain	1.0000
3:32818930:GAG:G	donor_gain	0.9900
3:32818933:G:GG	donor_gain	0.9900

AlphaMissense

5646 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:32818351:T:C	C91R	1.000
3:32818685:G:A	C202Y	1.000
3:32818714:T:A	C212S	1.000
3:32818714:T:C	C212R	1.000
3:32818715:G:C	C212S	1.000
3:32818716:C:G	C212W	1.000
3:32818723:T:A	C215S	1.000
3:32818723:T:C	C215R	1.000
3:32818724:G:A	C215Y	1.000
3:32818724:G:C	C215S	1.000
3:32818724:G:T	C215F	1.000
3:32818725:C:G	C215W	1.000
3:32818736:T:C	L219P	1.000
3:32818738:T:A	C220S	1.000
3:32818738:T:C	C220R	1.000
3:32818739:G:A	C220Y	1.000
3:32818739:G:C	C220S	1.000
3:32818739:G:T	C220F	1.000
3:32818740:C:G	C220W	1.000
3:32818747:T:A	C223S	1.000
3:32818747:T:C	C223R	1.000
3:32818748:G:A	C223Y	1.000
3:32818748:G:C	C223S	1.000
3:32818748:G:T	C223F	1.000
3:32818749:C:G	C223W	1.000
3:32818759:C:A	H227N	1.000
3:32818759:C:G	H227D	1.000
3:32818759:C:T	H227Y	1.000
3:32818761:C:A	H227Q	1.000
3:32818761:C:G	H227Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000037958 (3:32844147 A>G), RS1000041102 (3:32894545 C>G), RS1000058473 (3:32897459 A>C,G), RS1000085697 (3:32824715 G>T), RS1000164411 (3:32853408 C>A), RS1000171673 (3:32831920 C>T), RS1000172118 (3:32816860 C>T), RS1000203661 (3:32849679 CTTAA>C), RS1000206197 (3:32817521 C>T), RS1000213268 (3:32892331 C>G), RS1000217693 (3:32888563 G>A,T), RS1000244178 (3:32892644 C>A,T), RS1000268082 (3:32842201 T>C), RS1000268794 (3:32856138 C>G), RS1000370767 (3:32882339 A>C)

Disease associations

OMIM: gene MIM:618570 | disease phenotypes: MIM:618667, MIM:236600

GenCC curated gene-disease

Disease	Classification	Inheritance
hydrocephalus, congenital communicating, 1	Strong	Autosomal dominant

Mondo (2): hydrocephalus, congenital communicating, 1 (MONDO:0032862), congenital hydrocephalus (MONDO:0016349)

Orphanet (1): Congenital hydrocephalus (Orphanet:2185)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001250	Seizure
HP:0001334	Communicating hydrocephalus
HP:0002119	Ventriculomegaly
HP:0012758	Neurodevelopmental delay

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001251_14	Pulmonary function	4.000000e-06
GCST006979_58	Heel bone mineral density	5.000000e-19
GCST007995_15	Asthma (childhood onset)	3.000000e-10
GCST009391_1960	Metabolite levels	7.000000e-06
GCST009597_217	Multiple sclerosis	8.000000e-10
GCST009723_62	Vertical cup-disc ratio (adjusted for vertical disc diameter)	3.000000e-10
GCST009724_29	Vertical cup-disc ratio (multi-trait analysis)	6.000000e-14
GCST009798_68	Asthma	3.000000e-12
GCST90000025_730	Appendicular lean mass	9.000000e-17

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0009270	heel bone mineral density
EFO:0006939	cup-to-disc ratio measurement
EFO:0004980	appendicular lean mass

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
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Caffeine	decreases phosphorylation	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Urethane	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B5ND	PGPC14_26	Induced pluripotent stem cell	Female
CVCL_TU55	HAP1 TRIM71 (-) 1	Cancer cell line	Male
CVCL_TU56	HAP1 TRIM71 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06664372	Not specified	NOT_YET_RECRUITING	Insertion of Frontal Ventricular Catheter of VP Shunt in Congenital Hydrocephalus Guided by Trans Fontanelle Ultrasound