USP34

Summary

USP34 (ubiquitin specific peptidase 34, HGNC:20066) is a protein-coding gene on chromosome 2p15, encoding Ubiquitin carboxyl-terminal hydrolase 34 (Q70CQ2). Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway.

Enables cysteine-type deubiquitinase activity and cysteine-type endopeptidase activity. Involved in positive regulation of canonical Wnt signaling pathway and protein K48-linked deubiquitination. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 9736 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen)
• GWAS associations: 22
• Clinical variants (ClinVar): 567 total — 1 pathogenic
• MANE Select transcript: NM_014709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20066
Approved symbol	USP34
Name	ubiquitin specific peptidase 34
Location	2p15
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0570, KIAA0729
Ensembl gene	ENSG00000115464
Ensembl biotype	protein_coding
OMIM	615295
Entrez	9736

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 11 retained_intron, 6 protein_coding_CDS_not_defined, 4 protein_coding, 1 nonsense_mediated_decay

ENST00000398571, ENST00000411912, ENST00000436269, ENST00000453133, ENST00000453734, ENST00000460004, ENST00000463046, ENST00000467128, ENST00000468703, ENST00000472689, ENST00000472706, ENST00000476716, ENST00000482250, ENST00000483672, ENST00000484179, ENST00000487547, ENST00000490527, ENST00000490552, ENST00000492604, ENST00000492882, ENST00000494867, ENST00000498268

RefSeq mRNA: 1 — MANE Select: NM_014709 NM_014709

CCDS: CCDS42686

Canonical transcript exons

ENST00000398571 — 80 exons

Exon	Start	End
ENSE00000756987	61311784	61311910
ENSE00000756988	61314585	61314744
ENSE00000756989	61314875	61314974
ENSE00000756990	61317654	61317767
ENSE00000756992	61319173	61319327
ENSE00000756993	61325375	61325457
ENSE00000756996	61333882	61333971
ENSE00000756997	61339351	61339478
ENSE00000756998	61339566	61339681
ENSE00000757002	61347870	61348480
ENSE00000757018	61395183	61395233
ENSE00000810087	61214060	61214694
ENSE00000810107	61331276	61331371
ENSE00000962911	61311540	61311687
ENSE00000962912	61301354	61301454
ENSE00000962913	61300951	61301160
ENSE00001069995	61265984	61266167
ENSE00001069998	61257204	61257350
ENSE00001070000	61265397	61265557
ENSE00001070002	61257052	61257108
ENSE00001070010	61283409	61283449
ENSE00001070024	61281090	61281242
ENSE00001154622	61190271	61190414
ENSE00001190389	61236161	61236236
ENSE00001190397	61236325	61236389
ENSE00001190436	61256873	61256950
ENSE00001190449	61259711	61259776
ENSE00001190489	61284875	61284957
ENSE00001190496	61288677	61288877
ENSE00001190504	61293464	61293550
ENSE00001190513	61294949	61295032
ENSE00001190521	61295168	61295290
ENSE00001281245	61283145	61283269
ENSE00001281574	61236026	61236073
ENSE00001533945	61405708	61406128
ENSE00001533946	61420746	61420833
ENSE00001533950	61470650	61471087
ENSE00001744938	61187463	61188709
ENSE00003474716	61204497	61204601
ENSE00003475121	61370321	61370413
ENSE00003475547	61228827	61228995
ENSE00003478937	61246324	61246477
ENSE00003482844	61256384	61256478
ENSE00003490369	61221502	61221606
ENSE00003492266	61232452	61232532
ENSE00003497896	61206760	61206886
ENSE00003498575	61383269	61383336
ENSE00003502923	61296800	61296925
ENSE00003505096	61188910	61189069
ENSE00003511528	61235845	61235910
ENSE00003513989	61229548	61229633
ENSE00003521436	61222619	61222663
ENSE00003528703	61380169	61380361
ENSE00003528713	61203140	61203263
ENSE00003529050	61245210	61245288
ENSE00003532748	61349250	61349285
ENSE00003534682	61223248	61223296
ENSE00003548431	61211772	61211929
ENSE00003553242	61343815	61344029
ENSE00003561639	61394853	61395002
ENSE00003566041	61241560	61241655
ENSE00003568196	61280244	61280348
ENSE00003583499	61348756	61348886
ENSE00003584719	61190518	61190658
ENSE00003587300	61241766	61241819
ENSE00003597558	61278388	61278443
ENSE00003617472	61208899	61208977
ENSE00003625209	61227067	61227218
ENSE00003626688	61204256	61204380
ENSE00003627265	61378363	61378424
ENSE00003631607	61220310	61220457
ENSE00003645680	61370498	61370579
ENSE00003646578	61248511	61248683
ENSE00003657010	61228645	61228719
ENSE00003659157	61192901	61192980
ENSE00003667185	61206017	61206124
ENSE00003677232	61278165	61278285
ENSE00003682246	61223060	61223164
ENSE00003683318	61350568	61350693
ENSE00003691016	61350260	61350389

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.2548 / max 604.2985, expressed in 1809 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28653	12.9929	1740
28655	5.6231	1600
28650	3.6100	1424
28649	3.3842	1314
28651	1.5614	814
28640	0.9088	416
28643	0.8700	432
28652	0.7497	436
28654	0.5305	282
28641	0.0195	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.50	gold quality
nipple	UBERON:0002030	99.50	gold quality
cardia of stomach	UBERON:0001162	99.48	gold quality
pylorus	UBERON:0001166	99.38	gold quality
ventral tegmental area	UBERON:0002691	99.07	gold quality
trigeminal ganglion	UBERON:0001675	99.02	gold quality
superior surface of tongue	UBERON:0007371	98.99	gold quality
lateral globus pallidus	UBERON:0002476	98.85	gold quality
inferior vagus X ganglion	UBERON:0005363	98.85	gold quality
sperm	CL:0000019	98.71	gold quality
pericardium	UBERON:0002407	98.70	gold quality
subthalamic nucleus	UBERON:0001906	98.67	gold quality
superior vestibular nucleus	UBERON:0007227	98.61	gold quality
urethra	UBERON:0000057	98.58	gold quality
saphenous vein	UBERON:0007318	98.51	gold quality
pharyngeal mucosa	UBERON:0000355	98.49	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.44	gold quality
male germ cell	CL:0000015	98.40	gold quality
medulla oblongata	UBERON:0001896	98.35	gold quality
substantia nigra pars compacta	UBERON:0001965	98.25	gold quality
body of tongue	UBERON:0011876	98.15	gold quality
penis	UBERON:0000989	98.14	gold quality
tongue	UBERON:0001723	98.09	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.95	gold quality
periodontal ligament	UBERON:0008266	97.93	gold quality
corpus callosum	UBERON:0002336	97.86	gold quality
vena cava	UBERON:0004087	97.83	gold quality
secondary oocyte	CL:0000655	97.81	gold quality
superficial temporal artery	UBERON:0001614	97.79	gold quality
synovial joint	UBERON:0002217	97.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	836.55
E-ANND-3	yes	10.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

106 targeting USP34, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754

Literature-anchored findings (GeneRIF, showing 10)

• axin associates with ubiquitin-specific protease 34 (USP34); results indicate USP34 controls the levels of axin and positively modulate Wnt signaling by acting downstream of beta-catenin stabilization through controlling the nuclear accumulation of axin (PMID:21383061)
• CONCLUSIONS: USP34 gene polymorphisms (rs17008097 and rs17008940) may not be associated with Polycystic ovary syndrome in the Han Chinese women. (PMID:25975428)
• the role of USP34 on epithelial-mesenchymal (EMT) induction and its effects on mammary epithelial stem cells, was investigated. (PMID:28499884)
• data indicate that USP34 is required for osteogenic differentiation and bone formation. (PMID:30181118)
• USP34 may be a valuable marker for the assessment of patients with diffuse large Bcell lymphoma and further studies are needed to clarify USP34 expression on diffuse large Bcell lymphoma (PMID:30221700)
• The study unveils a previously unknown function of USP34 in regulating the metabolic stability of gp78. (PMID:30585151)
• The deubiquitinase USP34 stabilizes SOX2 and induces cell survival and drug resistance in laryngeal squamous cell carcinoma. (PMID:32783291)
• Structural Insights into the Catalytic Mechanism and Ubiquitin Recognition of USP34. (PMID:35588869)
• An siRNA library screen identifies CYLD and USP34 as deubiquitinases that regulate GPCR-p38 MAPK signaling and distinct inflammatory responses. (PMID:37865315)
• Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells. (PMID:38167292)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	USP34	ENSDARG00000102252
mus_musculus	Usp34	ENSMUSG00000056342
rattus_norvegicus	Usp34	ENSRNOG00000051889

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), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), 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 34 — Q70CQ2 (reviewed: Q70CQ2)

Alternative names: Deubiquitinating enzyme 34, Ubiquitin thioesterase 34, Ubiquitin-specific-processing protease 34

All UniProt accessions (5): A0A0C4DG73, Q70CQ2, H7BZ73, H7C150, H7C183

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins.

Subunit / interactions. Interacts with AXIN1 and AXIN2.

Tissue specificity. Expressed in brain at low level.

Similarity. Belongs to the peptidase C19 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q70CQ2-1	1	yes
Q70CQ2-2	2
Q70CQ2-3	3

RefSeq proteins (1): NP_055524* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018200	USP_CS	Conserved_site
IPR021905	DUF3517	Domain
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family
IPR056850	ARM_UBP34_24_USP9X_Y	Domain

Pfam: PF00443, PF12030, PF25010

UniProt features (76 total): strand 18, helix 15, modified residue 13, compositionally biased region 11, region of interest 4, turn 4, splice variant 3, sequence variant 3, active site 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7W3R	X-RAY DIFFRACTION	1.92
7W3U	X-RAY DIFFRACTION	3.13

Predicted structure (AlphaFold)

No AlphaFold model available for Q70CQ2 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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): 1903 (nucleophile); 2164 (proton acceptor)

Post-translational modifications (13): 352, 486, 487, 490, 649, 1469, 2488, 3358, 3359, 3381, 3386, 3406, 3503

Mutagenesis-validated functional residues (1):

Position	Phenotype
1903	loss of function.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 234 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, MARTINEZ_RB1_TARGETS_UP, TCF4_Q5, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, MYCMAX_01, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, WTGAAAT_UNKNOWN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_PROTEIN_K48_LINKED_DEUBIQUITINATION

GO Biological Process (8): proteolysis (GO:0006508), Wnt signaling pathway (GO:0016055), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), protein K48-linked deubiquitination (GO:0071108), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of signal transduction (GO:0009966), post-translational protein modification (GO:0043687)

GO Molecular Function (6): 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)

GO Cellular Component (2): nucleus (GO:0005634), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	1
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cysteine-type peptidase activity	2
protein metabolic process	1
cell surface receptor signaling pathway	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
protein deubiquitination	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
protein modification process	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
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP34	TDRD3	Q9H7E2	426
USP34	HSPBP1	Q9NZL4	408
USP34	CUL2	Q13617	381
USP34	MRPL15	Q9P015	336
USP34	PEX13	Q92968	331
USP34	PFAS	O15067	324
USP34	RNF146	Q9NTX7	322
USP34	PPP1R42	Q7Z4L9	307
USP34	ZUP1	Q96AP4	306
USP34	HRCT1	Q6UXD1	301
USP34	UBE2D4	Q9Y2X8	297
USP34	UNKL	Q9H9P5	296
USP34	SDK1	Q7Z5N4	292
USP34	SLC25A11	Q02978	289
USP34	HPD	P32754	289
USP34	GAL3ST3	Q96A11	289

IntAct

109 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
EIF3M	EIF3CL	psi-mi:“MI:0914”(association)	0.640
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
ZNF707	ZNF316	psi-mi:“MI:0914”(association)	0.530
ERMAP	AP3B1	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
SUV39H1	MAGEC1	psi-mi:“MI:0914”(association)	0.530
ZNF669	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF214	LRP4	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
SPATA46	MDM4	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
RPP21	POP7	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
ZNF785	TRIO	psi-mi:“MI:0914”(association)	0.530
AXIN1	UBC	psi-mi:“MI:0914”(association)	0.350
TNFSF13B	HEATR1	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
H1-6	SRSF10	psi-mi:“MI:0914”(association)	0.350

BioGRID (202): USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP34 (Affinity Capture-MS)

ESM2 similar proteins: A1Z7L1, A1ZBE8, A8WTE8, G5EEV2, O08662, O14981, O17237, O60287, O75691, P42173, P42858, P42859, P49815, P49816, P51111, P51112, P78527, Q21106, Q291E4, Q292H2, Q2KHT3, Q3UGY8, Q571H0, Q5JWR5, Q5SPP5, Q5TH69, Q5WNI9, Q5XG71, Q5ZKU4, Q61037, Q61QK6, Q641A2, Q70CQ2, Q80U30, Q8BL99, Q8IGJ0, Q8MYL1, Q8QGX4, Q8T626, Q9H0H0

Diamond homologs: A0A0R4IB93, A0JM59, A1CIL1, A1CW53, A2XDG4, A3AF13, A5PN09, A6QNM7, A7Z056, B1WBD7, B2GUZ1, B8NSV5, D3ZJ96, F6Z5C0, O22207, O60079, O94966, Q0CT11, Q0E2F9, Q0VA64, Q13107, Q2HJE4, Q2UUG8, Q3UJD6, Q3V0C5, Q4VSI4, Q5I043, Q5R5Z6, Q5RCD3, Q5ZM45, Q60MK8, Q6A4J8, Q6J1Y9, Q6PAW2, Q6U7I1, Q6ZQ93, Q70CQ2, Q76LT8, Q7JKC3, Q84WU2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	448
Likely benign	17
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
984375	NM_014709.4(USP34):c.8048-1053_8840+1025del	Pathogenic

SpliceAI

12249 predictions. Top by Δscore:

Variant	Effect	Δscore
2:61188706:TCAT:T	acceptor_gain	1.0000
2:61188707:CAT:C	acceptor_gain	1.0000
2:61188707:CATC:C	acceptor_gain	1.0000
2:61188709:TCTGT:T	acceptor_loss	1.0000
2:61188710:C:CC	acceptor_gain	1.0000
2:61188711:T:C	acceptor_loss	1.0000
2:61190269:AC:A	donor_gain	1.0000
2:61190269:ACC:A	donor_gain	1.0000
2:61190270:CC:C	donor_gain	1.0000
2:61190270:CCC:C	donor_gain	1.0000
2:61190410:TGAAC:T	acceptor_gain	1.0000
2:61190414:CCTGA:C	acceptor_loss	1.0000
2:61190415:C:CC	acceptor_gain	1.0000
2:61190415:CTGAA:C	acceptor_loss	1.0000
2:61190513:CGTA:C	donor_loss	1.0000
2:61190514:GTAC:G	donor_loss	1.0000
2:61190515:TACC:T	donor_loss	1.0000
2:61190654:GCAGA:G	acceptor_gain	1.0000
2:61190655:CAGA:C	acceptor_gain	1.0000
2:61190655:CAGAC:C	acceptor_gain	1.0000
2:61190657:GA:G	acceptor_gain	1.0000
2:61190659:C:CC	acceptor_gain	1.0000
2:61192988:T:C	acceptor_gain	1.0000
2:61192988:T:TC	acceptor_gain	1.0000
2:61203138:A:AC	donor_gain	1.0000
2:61203139:C:CC	donor_gain	1.0000
2:61203139:CT:C	donor_gain	1.0000
2:61203139:CTCAG:C	donor_gain	1.0000
2:61203143:G:C	donor_gain	1.0000
2:61204495:A:AC	donor_gain	1.0000

AlphaMissense

23668 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:61189065:A:G	L3293P	1.000
2:61192924:A:G	W3189R	1.000
2:61192924:A:T	W3189R	1.000
2:61192979:A:C	S3170R	1.000
2:61192979:A:T	S3170R	1.000
2:61203140:T:G	S3170R	1.000
2:61204371:C:T	G3090E	1.000
2:61204372:C:G	G3090R	1.000
2:61204372:C:T	G3090R	1.000
2:61204538:A:G	L3073P	1.000
2:61204550:A:G	L3069P	1.000
2:61204586:A:G	L3057P	1.000
2:61204595:A:G	L3054P	1.000
2:61206021:A:C	C3050W	1.000
2:61206045:A:C	S3042R	1.000
2:61206045:A:T	S3042R	1.000
2:61206047:T:G	S3042R	1.000
2:61206054:A:C	N3039K	1.000
2:61206054:A:T	N3039K	1.000
2:61206058:A:G	L3038P	1.000
2:61206061:A:G	L3037P	1.000
2:61206070:A:G	L3034P	1.000
2:61206079:G:T	A3031D	1.000
2:61206101:A:G	W3024R	1.000
2:61206101:A:T	W3024R	1.000
2:61206795:A:T	V3004D	1.000
2:61206813:A:G	L2998P	1.000
2:61206816:A:G	L2997P	1.000
2:61206844:A:G	C2988R	1.000
2:61206846:G:T	A2987D	1.000

dbSNP variants (sampled 300 via entrez): RS1000004546 (2:61443881 A>C,G), RS1000006832 (2:61343264 C>G), RS1000034464 (2:61276134 T>C), RS1000037184 (2:61257824 G>A), RS1000042820 (2:61205543 T>C), RS1000044574 (2:61451316 A>G), RS1000044827 (2:61317420 C>A,T), RS1000086552 (2:61324389 G>A,T), RS1000091647 (2:61200056 T>C), RS1000096666 (2:61451069 A>C), RS1000098966 (2:61195669 C>T), RS1000101377 (2:61376556 A>G), RS1000102245 (2:61285658 G>A), RS1000110548 (2:61387469 AAAC>A), RS1000116404 (2:61338260 G>A)

Disease associations

OMIM: gene MIM:615295 | disease phenotypes: MIM:612513

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (2): chromosome 2p16.1-p15 deletion syndrome (MONDO:0012916), congenital heart disease (MONDO:0005453)

Orphanet (1): 2p15p16.1 microdeletion syndrome (Orphanet:261349)

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST001438_15	Crohn’s disease	5.000000e-09
GCST004628_146	Immature fraction of reticulocytes	2.000000e-20
GCST004863_56	Mosquito bite size	9.000000e-06
GCST005983_30	Serum uric acid levels	3.000000e-08
GCST006414_113	Atrial fibrillation	6.000000e-09
GCST006627_47	Diastolic blood pressure	3.000000e-11
GCST006956_8	Erectile dysfunction	8.000000e-06
GCST007565_49	Morning person	7.000000e-17
GCST007576_56	Chronotype	7.000000e-17
GCST007725_35	Serum uric acid levels	8.000000e-10
GCST008059_217	Estimated glomerular filtration rate	9.000000e-08
GCST008157_15	Body fat mass	7.000000e-06
GCST008839_92	Height	2.000000e-12
GCST008971_30	Urate levels	1.000000e-07
GCST008972_11	Urate levels	4.000000e-12
GCST008972_132	Urate levels	3.000000e-06
GCST90002387_258	Immature fraction of reticulocytes	2.000000e-09
GCST90002387_259	Immature fraction of reticulocytes	8.000000e-18
GCST90002390_358	Mean corpuscular hemoglobin	8.000000e-17
GCST90002392_199	Mean corpuscular volume	3.000000e-21
GCST90002397_801	Mean spheric corpuscular volume	7.000000e-42
GCST90011900_2	Serum alkaline phosphatase levels	2.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0008378	mosquito bite reaction size measurement
EFO:0004761	uric acid measurement
EFO:0006336	diastolic blood pressure
EFO:0008328	chronotype measurement
EFO:0004531	urate measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
C567289	Chromosome 2p16.1-P15 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression, affects cotreatment, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Formaldehyde	decreases expression, increases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
lead acetate	affects cotreatment, increases expression	1
decabromobiphenyl ether	decreases expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2KL	Abcam HeLa USP34 KO	Cancer cell line	Female
CVCL_TW92	HAP1 USP34 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE