USP37

Summary

USP37 (ubiquitin specific peptidase 37, HGNC:20063) is a protein-coding gene on chromosome 2q35, encoding Ubiquitin carboxyl-terminal hydrolase 37 (Q86T82). Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response. It is a selective cancer dependency (DepMap: 71.1% of cell lines).

Enables cysteine-type deubiquitinase activity; cysteine-type endopeptidase activity; and protein kinase binding activity. Involved in G1/S transition of mitotic cell cycle; protein deubiquitination; and regulation of DNA replication. Located in nucleus.

Source: NCBI Gene 57695 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 114 total
• Cancer dependency (DepMap): dependent in 71.1% of screened cell lines
• MANE Select transcript: NM_020935

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20063
Approved symbol	USP37
Name	ubiquitin specific peptidase 37
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1594
Ensembl gene	ENSG00000135913
Ensembl biotype	protein_coding
OMIM	620226
Entrez	57695

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000258399, ENST00000338465, ENST00000415516, ENST00000418019, ENST00000454775, ENST00000466523, ENST00000473554, ENST00000475553, ENST00000478329, ENST00000484018, ENST00000486242, ENST00000864209, ENST00000864210, ENST00000864211, ENST00000864212, ENST00000864213, ENST00000864214, ENST00000864215, ENST00000938009, ENST00000938010, ENST00000938011, ENST00000952647

RefSeq mRNA: 1 — MANE Select: NM_020935 NM_020935

CCDS: CCDS2418

Canonical transcript exons

ENST00000258399 — 26 exons

Exon	Start	End
ENSE00000785738	218463306	218463366
ENSE00000876091	218488304	218488421
ENSE00000876097	218466010	218466176
ENSE00000876098	218459790	218459905
ENSE00000876099	218457092	218457161
ENSE00000876100	218455580	218455718
ENSE00000876101	218450251	218455017
ENSE00000922270	218495760	218495950
ENSE00000922275	218534609	218534706
ENSE00001333703	218560820	218560883
ENSE00001333704	218562673	218562813
ENSE00001709886	218568178	218568351
ENSE00002235042	218558498	218558677
ENSE00002292067	218549809	218549909
ENSE00003467534	218546221	218546298
ENSE00003543461	218479650	218479715
ENSE00003546661	218482070	218482234
ENSE00003552329	218476840	218476981
ENSE00003552414	218553553	218553724
ENSE00003582588	218498026	218498157
ENSE00003620812	218509979	218510140
ENSE00003650993	218474630	218474885
ENSE00003655131	218497734	218497857
ENSE00003658861	218546919	218547091
ENSE00003664831	218529956	218530040
ENSE00003679775	218485664	218485743

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 88.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9928 / max 210.4689, expressed in 1785 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33971	18.5303	1785
33970	0.2537	114
202573	0.2018	98
33968	0.0070	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	88.99	silver quality
secondary oocyte	CL:0000655	88.63	gold quality
adrenal tissue	UBERON:0018303	88.59	gold quality
calcaneal tendon	UBERON:0003701	87.71	gold quality
sperm	CL:0000019	87.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.33	gold quality
colonic epithelium	UBERON:0000397	85.88	gold quality
corpus callosum	UBERON:0002336	85.71	gold quality
thymus	UBERON:0002370	85.66	gold quality
upper arm skin	UBERON:0004263	85.20	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.86	silver quality
ventricular zone	UBERON:0003053	83.52	gold quality
oviduct epithelium	UBERON:0004804	83.50	gold quality
cartilage tissue	UBERON:0002418	83.15	gold quality
palpebral conjunctiva	UBERON:0001812	83.08	gold quality
bone marrow cell	CL:0002092	82.86	gold quality
testis	UBERON:0000473	82.53	gold quality
tonsil	UBERON:0002372	82.23	gold quality
buccal mucosa cell	CL:0002336	82.01	gold quality
visceral pleura	UBERON:0002401	81.85	gold quality
right testis	UBERON:0004534	81.68	gold quality
pancreatic ductal cell	CL:0002079	81.62	silver quality
nasal cavity epithelium	UBERON:0005384	81.43	gold quality
tendon	UBERON:0000043	81.36	gold quality
left testis	UBERON:0004533	81.34	gold quality
cortical plate	UBERON:0005343	81.01	gold quality
ganglionic eminence	UBERON:0004023	80.82	gold quality
sural nerve	UBERON:0015488	80.77	gold quality
parietal pleura	UBERON:0002400	80.49	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	6.00
E-MTAB-6678	no	3.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

286 targeting USP37, 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-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-190A-3P	100.00	80.35	5520
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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 71.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• The deubiquitinase USP37 binds CDH1 and removes degradative polyubiquitin from cyclin A. USP37 was induced by E2F factors in G1, peaked at G1/S, and was degraded in late mitosis. Phosphorylation of USP37 by CDK2 stimulated its full activity. (PMID:21596315)
• USP37 links REST to the control of p27 stability and cell proliferation. (PMID:22665064)
• Skp1-Cul1-F-box ubiquitin ligase (SCF(betaTrCP))-mediated destruction of the ubiquitin-specific protease USP37 during G2-phase promotes mitotic entry (PMID:23027877)
• our findings of USP37-modulating PLZF/RARA stability and cell transformation suggest that USP37 is a potential therapeutic target for PLZF/RARA-associated APL (PMID:23208507)
• These results suggested that the UIMs in USP37 contribute to the full enzymatic activity, but not ubiquitin chain substrate specificity, of USP37 possibly by holding the ubiquitin chain substrate in the proximity of the catalytic core. (PMID:24324262)
• USP37 is significantly upregulated in human lung cancer tissues, where its expression is positively correlated with c-Myc protein expression. (PMID:25284584)
• USP37 associates with cohesin and contributes to sister chromatid resolution. Cohesion defects are rescued by expression of an RNAi-resistant USP37, but not the catalytically impaired USP37(C350A) mutant. (PMID:26299517)
• USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. (PMID:27296872)
• these findings reveal a role for REST-associated G9a and histone H3K9 methylation in the repression of USP37 expression in medulloblastoma. Reactivation of USP37 by G9a inhibition has the potential for therapeutic applications in REST-expressing medulloblastomas (PMID:28483947)
• Findings reveal that USP37 is highly expressed in BCSCs and is correlated with poor prognosis in breast cancer patients. USP37 can regulate the stemness, cell invasion and EMT via Hh pathway, and decreased USP37 confers sensitivity to cisplatin in breast cancer cells. (PMID:30482232)
• The ubiquitin interacting motifs of USP37 act on the proximal Ub of a di-Ub chain to enhance catalytic efficiency. (PMID:30858488)
• USP37 promotes deubiquitination of HIF2alpha in kidney cancer. (PMID:32461361)
• USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin. (PMID:33390801)
• USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM. (PMID:34606619)
• The deubiquitinating enzyme USP37 promotes keloid fibroblasts proliferation and collagen production by regulating the c-Myc expression. (PMID:36333840)
• Ubiquitin specific peptidase 37 and PCNA interaction promotes osteosarcoma pathogenesis by modulating replication fork progression. (PMID:37118828)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp37	ENSDARG00000040990
mus_musculus	Usp37	ENSMUSG00000033364
rattus_norvegicus	Usp37	ENSRNOG00000022720

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), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), 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 37 — Q86T82 (reviewed: Q86T82)

Alternative names: Deubiquitinating enzyme 37, Ubiquitin thioesterase 37, Ubiquitin-specific-processing protease 37

All UniProt accessions (2): Q86T82, Q86W68

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response. Antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of ‘Lys-11’-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1. Also plays an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability. Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM. Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM. Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI. Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination.

Subunit / interactions. Interacts with FZR1/CDH1. Interacts with CDT1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in brain and prostate.

Post-translational modifications. Polyubiquitinated via ‘Lys-11’-linked ubiquitin by the APC(CDH1) complex during late mitosis, leading to its degradation. Able to mediate auto-deubiquitination. Phosphorylated at Ser-628 by CDK2 during G1/S phase but not during mitosis; phosphorylation at Ser-628 is required for deubiquitinase activity. Also polyubiquitinated during early G1 phase, without leading to degradation. Phosphorylated at Ser-114 by ATM following DNA damage, which in turn increases its deubiquitination activity towards BLM.

Domain organisation. The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination.

Induction. Induced by E2F transcription factors in G1.

Similarity. Belongs to the peptidase C19 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86T82-1	1	yes
Q86T82-2	2

RefSeq proteins (1): NP_065986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR003903	UIM_dom	Conserved_site
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, PF02809, PF16674

UniProt features (62 total): mutagenesis site 10, sequence conflict 8, compositionally biased region 7, modified residue 7, strand 7, short sequence motif 6, domain 4, region of interest 4, active site 2, splice variant 2, turn 2, chain 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3U12	X-RAY DIFFRACTION	2.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86T82-F1	63.69	0.30

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): 350 (nucleophile); 906 (proton acceptor)

Post-translational modifications (7): 114, 170, 210, 628, 650, 652, 770

Mutagenesis-validated functional residues (10):

Position	Phenotype
32–34	no effect.
71–74	no effect.
96–99	no effect.
114	loss of phosphorylation following cisplatin treatment.
160–163	no effect.
221–223	no effect.
350	abolishes deubiquitinase activity.
628	abolishes phosphorylation by cdk2, leading to lower deubiquitinase activity.
782–784	impaired interaction with fzr1/cdh1 and subsequent ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 234 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, E2F_Q4, TGCGCANK_UNKNOWN, E2F4DP1_01, GAANYNYGACNY_UNKNOWN, FISCHER_G1_S_CELL_CYCLE, GCM_ZNF198, GOBP_CELL_CYCLE_PHASE_TRANSITION, GCM_PPM1D, TGACCTY_ERR1_Q2, AATGGAG_MIR136, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, COUP_01, CAGCAGG_MIR370

GO Biological Process (8): G1/S transition of mitotic cell cycle (GO:0000082), regulation of DNA replication (GO:0006275), proteolysis (GO:0006508), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), protein K11-linked deubiquitination (GO:0035871), cell division (GO:0051301), protein K48-linked deubiquitination (GO:0071108)

GO Molecular Function (8): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), protein kinase binding (GO:0019901), 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), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein deubiquitination	2
cysteine-type peptidase activity	2
cellular anatomical structure	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
DNA replication	1
regulation of DNA metabolic process	1
protein metabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
cellular process	1
endopeptidase activity	1
deubiquitinase activity	1
kinase binding	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
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP37	USP28	Q96RU2	630
USP37	ZUP1	Q96AP4	614
USP37	USP17L2	Q6R6M4	592
USP37	BTRC	Q9Y297	574
USP37	USP7	Q93009	551
USP37	USP1	O94782	549
USP37	USP14	P54578	540
USP37	OTUB1	Q96FW1	536
USP37	ADRM1	Q16186	523
USP37	GLI1	P08151	519
USP37	USP13	Q92995	519
USP37	UCHL5	Q9Y5K5	515
USP37	USP39	Q53GS9	514
USP37	TTC19	Q6DKK2	512
USP37	WDR73	Q6P4I2	510

IntAct

16 interactions, top by confidence:

A	B	Type	Score
FBXW11	EEF2K	psi-mi:“MI:0914”(association)	0.640
FBXW11	AHCYL1	psi-mi:“MI:0914”(association)	0.530
FZR1	TK1	psi-mi:“MI:0914”(association)	0.530
FZR1	TK1	psi-mi:“MI:0914”(association)	0.350
BTRC	ACOT7	psi-mi:“MI:0914”(association)	0.350
FBXW11	PTCD1	psi-mi:“MI:0914”(association)	0.350
USP37	ALB	psi-mi:“MI:0914”(association)	0.350
FBXW11	OGT	psi-mi:“MI:0914”(association)	0.350
FZR1	CDK1	psi-mi:“MI:0914”(association)	0.350
FBXW11	BHLHE40	psi-mi:“MI:0914”(association)	0.350
BTRC	BHLHE40	psi-mi:“MI:0914”(association)	0.350
FBXW11	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
FZR1	BUB1B	psi-mi:“MI:0914”(association)	0.350

BioGRID (185): USP37 (Affinity Capture-Western), MYC (Affinity Capture-Western), MYC (Reconstituted Complex), USP37 (Affinity Capture-Western), MYC (Biochemical Activity), USP37 (Affinity Capture-MS), USP37 (Affinity Capture-Western), USP37 (Affinity Capture-Western), USP37 (Biochemical Activity), USP37 (Affinity Capture-MS), USP37 (Affinity Capture-Western), YWHAG (Affinity Capture-Western), USP37 (Reconstituted Complex), SMC3 (Proximity Label-MS), SMC1A (Proximity Label-MS)

ESM2 similar proteins: A0JM59, A2BGT0, A4QNN3, A5PMR2, A5PN09, A6QNM7, A7Z056, A8HAL1, B1AY15, B1WBD7, D3ZPG5, E1C213, E2RK09, E7F6T8, E9QG68, F1N5V1, F1SRY5, P51944, P52479, P97573, Q0VA64, Q14155, Q15052, Q28CN3, Q2KJ09, Q3KR59, Q3UN04, Q5R5Z6, Q5RE63, Q5REG5, Q5XXR3, Q70CQ3, Q70CQ4, Q70EK9, Q86T82, Q8BW70, Q8C0R0, Q8C2S0, Q8C6M1, Q8K4I3

Diamond homologs: A1CIL1, A1CW53, A2Q9N1, A2XDG4, A3AF13, A4FUN7, A5D9H7, A5WWB0, A6QR55, B0Y4P5, B2GUZ1, B8NSV5, C0HB46, D0RB01, E1C213, E2RK09, E7F6T8, F1M625, F1N5V1, F1SRY5, F6Z5C0, M9PD06, O24454, O74442, O75317, O94782, O94966, P34547, P35123, P38187, P39967, P40818, P43593, P50102, P51784, P62068, P62069, Q01988, Q0CT11, Q0E2F9

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
CDK2	“up-regulates activity”	USP37	phosphorylation
CyclinA2/CDK2	“up-regulates activity”	USP37	phosphorylation
E2F1	“up-regulates quantity by expression”	USP37	“transcriptional regulation”
APC-c	“down-regulates quantity by destabilization”	USP37	ubiquitination
USP37	“up-regulates quantity by stabilization”	CCNA2	deubiquitination
CyclinE/CDK2	“up-regulates activity”	USP37	phosphorylation
USP37	“down-regulates activity”	FZR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4276 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218455574:TCTTA:T	donor_loss	1.0000
2:218455575:CTTAC:C	donor_loss	1.0000
2:218455576:TTA:T	donor_loss	1.0000
2:218455577:TAC:T	donor_loss	1.0000
2:218455578:A:AC	donor_gain	1.0000
2:218455578:ACTTG:A	donor_loss	1.0000
2:218455579:C:CA	donor_gain	1.0000
2:218455579:CT:C	donor_gain	1.0000
2:218455579:CTT:C	donor_gain	1.0000
2:218455715:TGAC:T	acceptor_gain	1.0000
2:218455717:ACC:A	acceptor_loss	1.0000
2:218455718:CCT:C	acceptor_loss	1.0000
2:218455719:C:CC	acceptor_gain	1.0000
2:218455719:CT:C	acceptor_loss	1.0000
2:218455720:T:G	acceptor_loss	1.0000
2:218457087:TTCA:T	donor_loss	1.0000
2:218457088:TCA:T	donor_loss	1.0000
2:218457089:CACCT:C	donor_loss	1.0000
2:218457091:C:A	donor_loss	1.0000
2:218457158:CTGT:C	acceptor_gain	1.0000
2:218459785:ATTAC:A	donor_loss	1.0000
2:218459787:TACC:T	donor_loss	1.0000
2:218459789:C:CT	donor_loss	1.0000
2:218459789:CCT:C	donor_gain	1.0000
2:218459901:AAACT:A	acceptor_gain	1.0000
2:218459902:AACT:A	acceptor_gain	1.0000
2:218459903:ACT:A	acceptor_gain	1.0000
2:218459903:ACTC:A	acceptor_loss	1.0000
2:218459904:CT:C	acceptor_gain	1.0000
2:218459904:CTC:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005302 (2:218546152 C>T), RS1000008154 (2:218525480 T>C), RS1000079946 (2:218569737 C>G), RS1000113053 (2:218565814 C>T), RS1000113412 (2:218554151 T>C), RS1000152940 (2:218487697 G>T), RS1000185515 (2:218467018 A>T), RS1000188781 (2:218518589 T>C), RS1000225484 (2:218487448 G>A,C), RS1000225938 (2:218507486 A>T), RS1000237803 (2:218467410 G>A), RS1000272831 (2:218488048 G>A), RS1000276428 (2:218525752 T>C), RS1000312796 (2:218467325 A>G), RS1000381199 (2:218520371 CAG>C)

Disease associations

OMIM: gene MIM:620226 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002783_137	Body mass index	4.000000e-07
GCST002783_324	Body mass index	5.000000e-07
GCST002783_602	Body mass index	7.000000e-09
GCST003264_1024	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST006661_114	Male-pattern baldness	2.000000e-16
GCST008163_192	Height	2.000000e-07
GCST90002385_461	High light scatter reticulocyte count	2.000000e-31
GCST90002386_275	High light scatter reticulocyte percentage of red cells	2.000000e-22
GCST90002405_1	Reticulocyte count	9.000000e-23
GCST90002406_69	Reticulocyte fraction of red cells	2.000000e-15
GCST90020028_763	Hip circumference adjusted for BMI	8.000000e-14
GCST90020029_983	Waist circumference adjusted for body mass index	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004713	FEV/FVC ratio
EFO:0007986	reticulocyte count
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression, increases expression	1
bleomycetin	decreases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vincristine	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Amosite	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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