USP29

Summary

USP29 (ubiquitin specific peptidase 29, HGNC:18563) is a protein-coding gene on chromosome 19q13.43, encoding Ubiquitin carboxyl-terminal hydrolase 29 (Q9HBJ7). Deubiquitinase involved in innate antiviral immunity by mediating ‘Lys-48’-linked deubiquitination of CGAS, thereby promoting its stabilization.

Predicted to enable cysteine-type deubiquitinase activity and cysteine-type endopeptidase activity. Predicted to be involved in several processes, including G1/S transition of mitotic cell cycle; positive regulation of type I interferon-mediated signaling pathway; and protein K48-linked deubiquitination. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 57663 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 141 total
• MANE Select transcript: NM_020903

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18563
Approved symbol	USP29
Name	ubiquitin specific peptidase 29
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131864
Ensembl biotype	protein_coding
OMIM	609546
Entrez	57663

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000254181, ENST00000598197, ENST00000600020, ENST00000600940

RefSeq mRNA: 4 — MANE Select: NM_020903 NM_001389643, NM_001426405, NM_001426406, NM_020903

CCDS: CCDS33124

Canonical transcript exons

ENST00000254181 — 4 exons

Exon	Start	End
ENSE00001469930	57124039	57124139
ENSE00001469931	57122325	57122474
ENSE00002256070	57119985	57120229
ENSE00002982498	57128660	57131926

Expression profiles

Bgee: expression breadth broad, 63 present calls, max score 81.73.

Top tissues by expression

220 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	81.73	silver quality
diaphragm	UBERON:0001103	66.83	gold quality
sperm	CL:0000019	66.17	gold quality
male germ cell	CL:0000015	65.45	gold quality
right testis	UBERON:0004534	63.85	gold quality
left testis	UBERON:0004533	63.83	gold quality
testis	UBERON:0000473	63.11	gold quality
cervix squamous epithelium	UBERON:0006922	62.31	gold quality
upper arm skin	UBERON:0004263	58.68	gold quality
tibialis anterior	UBERON:0001385	55.00	silver quality
pancreatic ductal cell	CL:0002079	52.73	silver quality
cervix epithelium	UBERON:0004801	52.25	gold quality
deltoid	UBERON:0001476	52.22	gold quality
mucosa of urinary bladder	UBERON:0001259	50.73	gold quality
oviduct epithelium	UBERON:0004804	50.26	gold quality
nasal cavity epithelium	UBERON:0005384	50.02	gold quality
hair follicle	UBERON:0002073	50.00	gold quality
epithelial cell of pancreas	CL:0000083	49.94	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.90	gold quality
quadriceps femoris	UBERON:0001377	49.81	gold quality
nephron tubule	UBERON:0001231	49.04	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
thymus	UBERON:0002370	48.53	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	48.46	silver quality
adult organism	UBERON:0007023	48.46	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FUBP1, TP53

Literature-anchored findings (GeneRIF, showing 8)

• USP29 interacts with Claspin and is able to deubiquitinate it both in vivo and in vitro. (PMID:24632611)
• USP29 maintains the stability of cGAS and promotes cellular antiviral responses and autoimmunity. (PMID:32457395)
• Deubiquitinase USP29 promotes gastric cancer cell migration by cooperating with phosphatase SCP1 to stabilize Snail protein. (PMID:32973332)
• Self-stabilizing regulation of deubiquitinating enzymes in an enzymatic activity-dependent manner. (PMID:33864866)
• Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis. (PMID:34071237)
• USP29 coordinates MYC and HIF1alpha stabilization to promote tumor metabolism and progression. (PMID:34601505)
• The Deubiquitinase USP29 Promotes SARS-CoV-2 Virulence by Preventing Proteasome Degradation of ORF9b. (PMID:35638730)
• Phosphorylation of USP29 by CDK1 Governs TWIST1 Stability and Oncogenic Functions. (PMID:36782089)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Usp29	ENSMUSG00000051527
rattus_norvegicus	Usp29	ENSRNOG00000015956

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242), USP32 (ENSG00000170832)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 29 — Q9HBJ7 (reviewed: Q9HBJ7)

Alternative names: Deubiquitinating enzyme 29, Ubiquitin thioesterase 29, Ubiquitin-specific-processing protease 29

All UniProt accessions (3): Q9HBJ7, M0QZL0, M0R2Y1

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase involved in innate antiviral immunity by mediating ‘Lys-48’-linked deubiquitination of CGAS, thereby promoting its stabilization.

Subcellular location. Cytoplasm. Perinuclear region.

Similarity. Belongs to the peptidase C19 family.

RefSeq proteins (4): NP_001376572, NP_001413334, NP_001413335, NP_065954* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR032069	USP37-like_PH	Domain
IPR038093	USP37-like_PH_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443, PF16674

UniProt features (8 total): active site 2, sequence variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBJ7-F1	59.25	0.27

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 (2): 294 (nucleophile); 840 (proton acceptor)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY

GO Biological Process (10): G1/S transition of mitotic cell cycle (GO:0000082), proteolysis (GO:0006508), regulation of protein stability (GO:0031647), innate immune response (GO:0045087), protein stabilization (GO:0050821), defense response to virus (GO:0051607), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), protein K48-linked deubiquitination (GO:0071108), immune system process (GO:0002376), protein deubiquitination (GO:0016579)

GO Molecular Function (7): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), deubiquitinase activity (GO:0101005)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cysteine-type peptidase activity	2
cytoplasm	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
protein metabolic process	1
regulation of biological quality	1
immune response	1
defense response to symbiont	1
regulation of protein stability	1
defense response	1
response to virus	1
positive regulation of cytokine-mediated signaling pathway	1
positive regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
protein deubiquitination	1
biological_process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
endopeptidase activity	1
deubiquitinase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
ubiquitin-like protein peptidase activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1001 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP29	ZIM3	Q96PE6	713
USP29	ZIM2	Q9NZV7	666
USP29	USP7	Q93009	583
USP29	USP28	Q96RU2	562
USP29	USP49	Q70CQ1	545
USP29	ZUP1	Q96AP4	545
USP29	USP5	P45974	543
USP29	USP20	Q9Y2K6	531
USP29	OTUB1	Q96FW1	521
USP29	USP1	O94782	520
USP29	USP13	Q92995	519
USP29	AIMP2	Q13155	507
USP29	PEG3	P78418	507
USP29	USP44	Q9H0E7	507
USP29	CLSPN	Q9HAW4	503

IntAct

7 interactions, top by confidence:

A	B	Type	Score
AURKB	USP29	psi-mi:“MI:0915”(physical association)	0.500
CTSB	USP29	psi-mi:“MI:0915”(physical association)	0.400
USP29	RFWD3	psi-mi:“MI:0915”(physical association)	0.400
TP53	USP29	psi-mi:“MI:0915”(physical association)	0.400
USP29	HSPA1B	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): ZEB1 (Affinity Capture-Western), USP29 (Affinity Capture-Western), USP29 (PCA), USP29 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), USP29 (Reconstituted Complex), MAVS (Affinity Capture-Western), USP29 (Affinity Capture-Western), SNAI1 (Affinity Capture-Western), EPAS1 (Affinity Capture-Western), USP29 (Affinity Capture-Western), MB21D1 (Affinity Capture-Western), USP29 (Affinity Capture-Western), SNAI1 (Affinity Capture-Western), SNAI1 (Biochemical Activity)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A2AGB2, A2AKX3, A2ALV5, A6QNQ6, A8MT70, B0S6S9, B1WC58, D3Z987, F6SNN2, P56716, P70347, Q0P5X5, Q28FY7, Q2M2Z5, Q3U0P1, Q3V089, Q5CZC0, Q5DTT3, Q5RCM2, Q5T1N1, Q5T4T6, Q5VWN6, Q5VXU9, Q5W0Q7, Q69ZR9, Q6ZP01, Q7Z333, Q7Z4H7, Q7ZZH7, Q80WQ8, Q86V20, Q86YC2, Q8CCC3, Q8R3P9, Q8WP21, Q92844, Q96QP1

Diamond homologs: A0JM59, A5PMR2, A5PN09, A6H8I0, A6NNY8, A6QNM7, A7Z056, A8MUK1, B1AY13, B1WBD7, C9J2P7, C9JJH3, C9JLJ4, C9JPN9, C9JVI0, D3ZJ96, D6R901, D6R9N7, D6RA61, D6RBM5, D6RBQ6, D6RCP7, D6RJB6, E1C213, E2RK09, E7F6T8, F1N5V1, F1SRY5, F6Z5C0, F8VPZ3, M9PD06, O00507, O60079, O74442, O94966, O96612, P0C7I0, P0C8Z3, P35125, P39538

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	129
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

421 predictions. Top by Δscore:

Variant	Effect	Δscore
19:57124037:A:AG	acceptor_gain	1.0000
19:57124038:G:GA	acceptor_gain	1.0000
19:57124135:GAACT:G	donor_gain	1.0000
19:57124140:G:GG	donor_gain	1.0000
19:57120107:T:G	donor_gain	0.9900
19:57120230:G:GG	donor_gain	0.9900
19:57122471:AACT:A	donor_gain	0.9900
19:57122472:ACT:A	donor_gain	0.9900
19:57122472:ACTG:A	donor_loss	0.9900
19:57122473:CT:C	donor_gain	0.9900
19:57122473:CTG:C	donor_loss	0.9900
19:57122474:TGTA:T	donor_loss	0.9900
19:57122475:G:GG	donor_gain	0.9900
19:57122475:G:T	donor_loss	0.9900
19:57122476:T:A	donor_loss	0.9900
19:57124034:CCTA:C	acceptor_loss	0.9900
19:57124035:CTA:C	acceptor_loss	0.9900
19:57124036:TA:T	acceptor_loss	0.9900
19:57124038:G:A	acceptor_loss	0.9900
19:57124038:GTA:G	acceptor_gain	0.9900
19:57124038:GTAAC:G	acceptor_gain	0.9900
19:57124136:AACT:A	donor_gain	0.9900
19:57124137:ACTGT:A	donor_loss	0.9900
19:57124138:CT:C	donor_gain	0.9900
19:57124138:CTGTG:C	donor_loss	0.9900
19:57124139:TGTGA:T	donor_loss	0.9900
19:57124140:G:A	donor_loss	0.9900
19:57124141:T:G	donor_loss	0.9900
19:57124142:G:GG	donor_loss	0.9900
19:57124143:A:AC	donor_loss	0.9900

AlphaMissense

6177 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:57131232:T:A	W853R	0.993
19:57131232:T:C	W853R	0.993
19:57131154:A:C	S827R	0.992
19:57131156:T:A	S827R	0.992
19:57131156:T:G	S827R	0.992
19:57131248:A:T	D858V	0.991
19:57131319:T:G	Y882D	0.991
19:57131202:A:C	S843R	0.990
19:57131204:C:A	S843R	0.990
19:57131204:C:G	S843R	0.990
19:57129566:T:A	N297K	0.989
19:57129566:T:G	N297K	0.989
19:57129768:T:C	F365L	0.989
19:57129770:T:A	F365L	0.989
19:57129770:T:G	F365L	0.989
19:57129801:T:C	F376L	0.989
19:57129803:T:A	F376L	0.989
19:57129803:T:G	F376L	0.989
19:57131163:A:C	S830R	0.989
19:57131165:C:A	S830R	0.989
19:57131165:C:G	S830R	0.989
19:57131248:A:C	D858A	0.989
19:57129802:T:C	F376S	0.988
19:57129542:T:A	N289K	0.986
19:57129542:T:G	N289K	0.986
19:57129557:T:G	C294W	0.985
19:57129956:T:A	N427K	0.985
19:57129956:T:G	N427K	0.985
19:57129826:T:C	L384P	0.983
19:57131304:G:T	G877W	0.983

dbSNP variants (sampled 300 via entrez): RS1000838162 (19:57126027 A>C), RS1000842628 (19:57127069 G>T), RS1000849117 (19:57131217 T>A), RS1001220970 (19:57130703 G>A,C,T), RS1001421708 (19:57119025 A>G,T), RS1001636705 (19:57121103 T>C), RS1001741167 (19:57124257 T>C), RS1001863368 (19:57120086 C>T), RS1002008518 (19:57119693 G>C), RS1002115047 (19:57125787 G>A), RS1002254522 (19:57132307 C>G,T), RS1002593583 (19:57125456 G>T), RS1002823062 (19:57125393 G>A,C), RS1002852961 (19:57128729 G>A), RS1002884426 (19:57122449 A>G,T)

Disease associations

OMIM: gene MIM:609546 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002830_31	Urate levels in lean individuals	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate 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, affects methylation	2
bisphenol F	decreases methylation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2-palmitoylglycerol	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Valproic Acid	increases methylation	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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