DTX1

Summary

DTX1 (deltex E3 ubiquitin ligase 1, HGNC:3060) is a protein-coding gene on chromosome 12q24.13, encoding E3 ubiquitin-protein ligase DTX1 (Q86Y01). Functions as a ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity.

Studies in Drosophila have identified this gene as encoding a positive regulator of the Notch-signaling pathway. The human gene encodes a protein of unknown function; however, it may play a role in basic helix-loop-helix transcription factor activity.

Source: NCBI Gene 1840 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 96 total — 1 pathogenic
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_004416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3060
Approved symbol	DTX1
Name	deltex E3 ubiquitin ligase 1
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	hDx-1, RNF140
Ensembl gene	ENSG00000135144
Ensembl biotype	protein_coding
OMIM	602582
Entrez	1840

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000257600, ENST00000547730, ENST00000547974, ENST00000548759, ENST00000553140, ENST00000929430

RefSeq mRNA: 1 — MANE Select: NM_004416 NM_004416

CCDS: CCDS9164

Canonical transcript exons

ENST00000548759 — 10 exons

Exon	Start	End
ENSE00000917979	113077424	113078105
ENSE00002362374	113056730	113056944
ENSE00002419206	113057449	113058451
ENSE00003503332	113095325	113095414
ENSE00003519027	113093162	113093223
ENSE00003550664	113095042	113095203
ENSE00003583181	113093539	113093700
ENSE00003630210	113094038	113094099
ENSE00003689741	113094789	113094947
ENSE00003925214	113096715	113098025

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 92.75.

FANTOM5 (CAGE): breadth broad, TPM avg 3.9525 / max 472.0806, expressed in 553 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128130	2.8249	511
128132	0.4808	191
128131	0.2116	117
128129	0.1375	77
128134	0.0677	17
206902	0.0531	23
128138	0.0446	13
128135	0.0304	9
206901	0.0256	12
128139	0.0229	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.75	gold quality
spleen	UBERON:0002106	91.81	gold quality
right frontal lobe	UBERON:0002810	91.24	gold quality
anterior cingulate cortex	UBERON:0009835	90.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.23	gold quality
nucleus accumbens	UBERON:0001882	89.83	gold quality
cerebellar hemisphere	UBERON:0002245	89.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.56	gold quality
cerebellar cortex	UBERON:0002129	89.52	gold quality
amygdala	UBERON:0001876	89.50	gold quality
ganglionic eminence	UBERON:0004023	89.40	gold quality
prefrontal cortex	UBERON:0000451	89.34	gold quality
epithelial cell of pancreas	CL:0000083	88.76	silver quality
cerebellum	UBERON:0002037	88.63	gold quality
putamen	UBERON:0001874	88.40	gold quality
caudate nucleus	UBERON:0001873	88.39	gold quality
hypothalamus	UBERON:0001898	88.34	gold quality
right lobe of liver	UBERON:0001114	88.20	gold quality
neocortex	UBERON:0001950	88.19	gold quality
lymph node	UBERON:0000029	88.04	gold quality
frontal cortex	UBERON:0001870	87.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.84	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.90	gold quality
cerebral cortex	UBERON:0000956	86.77	gold quality
omental fat pad	UBERON:0010414	86.70	gold quality
peritoneum	UBERON:0002358	86.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.52	gold quality
forebrain	UBERON:0001890	86.38	gold quality
brain	UBERON:0000955	86.34	gold quality
temporal lobe	UBERON:0001871	86.16	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	18.06
E-ANND-3	yes	5.80
E-CURD-122	yes	5.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ERBB2	Activation

Upstream regulators (CollecTRI, top): GATA3, GFI1B, HES1, ID1, IKZF1, NOTCH1, RBPJ, RUNX1, TCF3

miRNA regulators (miRDB)

50 targeting DTX1, 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-4455	100.00	65.48	1587
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-6754-5P	98.60	65.54	1627

Literature-anchored findings (GeneRIF, showing 11)

• characterization of two genes expressed in centroblasts of human tonsils: deltex (Drosophila) homolog 1 (DTX1), which is related to the Notch pathway and a new Kelch-like protein, KLHL6 (PMID:12617994)
• It is reported that BBAP and the human family of DTX proteins (DTX1, DTX2, and DTX3) function as E3 ligases based on their capacity for self-ubiquitination. (PMID:12670957)
• this study reports the identification of two new hGIP-interacting partners, DTX1 and STAU1. (PMID:23395680)
• Two SNPs (rs2384077 and rs10744794) in an intron of DTX1 and the linkage disequilibrium (LD) block are significantly associated with the immune response to HBV vaccination. (PMID:26894927)
• Data indicate that decreased expression of deltex E3 ubiquitin ligase 1 (DTX1) in head and neck squamous cell carcinoma (HNSCC) tumors maybe associated with NOTCH pathway activation and increased migration potential. (PMID:28146432)
• Deltex-1 mutations predict poor survival in diffuse large B-cell lymphoma (PMID:28183850)
• DTX1 is an E3 ligase for c-FLIP in gastric cancer cells. (PMID:29374180)
• PI5P4Kgamma positively regulates the DTX1-mediated Notch pathway by promoting receptor recycling (PMID:29440432)
• frameshift mutations in DTX1 and NLRC5, two genes involved in immune regulation, were identified in a family with familial pityriasis rubra pilaris. (PMID:29704870)
• DTX1 rs1732786 single nucleotide polymorphism is associated with lung Cancer. (PMID:31313037)
• Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis. (PMID:32700476)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000102042
mus_musculus	Dtx1	ENSMUSG00000029603
rattus_norvegicus	Dtx1	ENSRNOG00000050848

Paralogs (4): DTX2 (ENSG00000091073), DTX4 (ENSG00000110042), DTX3L (ENSG00000163840), DTX3 (ENSG00000178498)

Protein

Protein identifiers

E3 ubiquitin-protein ligase DTX1 — Q86Y01 (reviewed: Q86Y01)

Alternative names: Protein deltex-1, RING-type E3 ubiquitin transferase DTX1

All UniProt accessions (1): Q86Y01

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity. Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Mainly acts as a positive regulator of Notch, but it also acts as a negative regulator, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Involved in neurogenesis, lymphogenesis and myogenesis, and may also be involved in MZB (Marginal zone B) cell differentiation. Promotes B-cell development at the expense of T-cell development, suggesting that it can antagonize NOTCH1.

Subunit / interactions. Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1 via its N-terminal region and EIF3F, the interaction is required for NOTCH1 deubiquitination. Interacts with EP300. Forms a heterodimer with BBAP; the heterodimerization leading to an increase of in vitro ubiquitin ligase activity. Interacts with ITCH.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed. Strongly expressed in blood vessel. Also expressed in embryonic nervous system, pancreas, lung, adrenal gland, digestive tube and muscles. Expressed in MZB cells and developing B- and T-cells.

Post-translational modifications. Ubiquitinated; undergoes ‘Lys-29’-linked polyubiquitination catalyzed by ITCH.

Domain organisation. The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases.

Induction. Regulated by NOTCH2.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the Deltex family.

RefSeq proteins (1): NP_004407* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR004170	WWE_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018123	WWE-dom_subgr	Domain
IPR037197	WWE_dom_sf	Homologous_superfamily
IPR039396	Deltex_C	Domain
IPR039398	Deltex_fam	Family
IPR039399	Deltex_C_sf	Homologous_superfamily

Pfam: PF02825, PF18102

UniProt features (63 total): strand 26, helix 11, turn 9, sequence conflict 5, compositionally biased region 4, region of interest 3, domain 2, chain 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6Y5P	X-RAY DIFFRACTION	1.74
8R5N	X-RAY DIFFRACTION	1.81
6Y5N	X-RAY DIFFRACTION	1.88
8R6A	X-RAY DIFFRACTION	2.4
8R6B	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86Y01-F1	76.10	0.46

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus

MSigDB gene sets: 235 (showing top): AHRARNT_01, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, PAX4_01, MODULE_169, GOBP_RESPONSE_TO_PEPTIDE, CMYB_01, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, MORI_IMMATURE_B_LYMPHOCYTE_UP, GOBP_NEUROGENESIS, CACCAGC_MIR138, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_ADHESION

GO Biological Process (12): DNA-templated transcription (GO:0006351), transcription by RNA polymerase II (GO:0006366), cell surface receptor signaling pathway (GO:0007166), Notch signaling pathway (GO:0007219), regulation of Notch signaling pathway (GO:0008593), glial cell differentiation (GO:0010001), protein ubiquitination (GO:0016567), T cell differentiation (GO:0030217), negative regulation of T cell differentiation (GO:0045581), negative regulation of neuron differentiation (GO:0045665), cellular response to leukemia inhibitory factor (GO:1990830), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (9): transcription coactivator activity (GO:0003713), Notch binding (GO:0005112), zinc ion binding (GO:0008270), SH3 domain binding (GO:0017124), ubiquitin protein ligase binding (GO:0031625), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by NOTCH1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
gene expression	1
RNA biosynthetic process	1
signal transduction	1
cell surface receptor signaling pathway	1
Notch signaling pathway	1
regulation of signal transduction	1
cell differentiation	1
gliogenesis	1
protein modification by small protein conjugation	1
lymphocyte differentiation	1
T cell activation	1
T cell differentiation	1
regulation of T cell differentiation	1
negative regulation of lymphocyte differentiation	1
negative regulation of T cell activation	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
signaling receptor binding	1
transition metal ion binding	1
protein domain specific binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1071 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DTX1	NOTCH1	P46531	850
DTX1	RBPJ	Q06330	793
DTX1	NRARP	Q7Z6K4	770
DTX1	ANK1	P16157	758
DTX1	ANK2	Q01484	757
DTX1	ANK3	Q12955	754
DTX1	NOTCH2	Q04721	752
DTX1	DTX3L	Q8TDB6	738
DTX1	DNER	Q8NFT8	727
DTX1	MAML1	Q92585	701
DTX1	NKAP	Q8N5F7	677
DTX1	PTCRA	Q6ISU1	653
DTX1	HEY1	Q9Y5J3	651
DTX1	NOTCH3	Q9UM47	588
DTX1	DLL1	O00548	575

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PRKAR1A	DTX1	psi-mi:“MI:0915”(physical association)	0.560
Eif3f	DTX1	psi-mi:“MI:0915”(physical association)	0.500
Eif3f	EIF3A	psi-mi:“MI:0914”(association)	0.500
DTX1	ITCH	psi-mi:“MI:0915”(physical association)	0.460
DTX1	ITCH	psi-mi:“MI:0403”(colocalization)	0.460
CRK	DTX1	psi-mi:“MI:0915”(physical association)	0.400
DTX1	UBC	psi-mi:“MI:0915”(physical association)	0.400
DTX1	Itch	psi-mi:“MI:0915”(physical association)	0.400
UBE2C	DTX1	psi-mi:“MI:0915”(physical association)	0.370
DTX1	UBE2D1	psi-mi:“MI:0915”(physical association)	0.370
DTX1	UBE2D2	psi-mi:“MI:0915”(physical association)	0.370
DTX1	UBE2D3	psi-mi:“MI:0915”(physical association)	0.370
UBE2D4	DTX1	psi-mi:“MI:0915”(physical association)	0.370
DTX1	UBE2E1	psi-mi:“MI:0915”(physical association)	0.370
UBE2N	DTX1	psi-mi:“MI:0915”(physical association)	0.370
DTX1	UBE2U	psi-mi:“MI:0915”(physical association)	0.370
DTX1	DEFA5	psi-mi:“MI:0915”(physical association)	0.370
G3BP1	DTX1	psi-mi:“MI:0915”(physical association)	0.370
Eif3f	Notch1	psi-mi:“MI:0914”(association)	0.350
DTX1	Lamp1	psi-mi:“MI:0403”(colocalization)	0.270
PRKAR1A	DTX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): DTX1 (PCA), CFLAR (Affinity Capture-Western), DTX1 (Reconstituted Complex), NOTCH1 (Co-localization), DTX1 (Biochemical Activity), DTX3L (Affinity Capture-Western), DTX1 (Affinity Capture-Western), DTX1 (Affinity Capture-Western), DTX1 (Affinity Capture-Western), EP300 (Two-hybrid), DTX1 (Two-hybrid), TMEM126A (Affinity Capture-MS), TOMM20 (Affinity Capture-MS), DTX1 (Affinity Capture-MS), DTX1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A4QP16, A6NP61, B2RVL6, C0SPG1, C3VD30, K7SGN7, O54880, P56163, Q1XFL1, Q29RJ0, Q2KI52, Q32L09, Q3V0J4, Q4R2Y2, Q4R739, Q58D79, Q5RAK6, Q5TKR9, Q5VWQ0, Q6PDK8, Q768S4, Q7T3T8, Q7T3T9, Q80T69, Q86US8, Q86Y01, Q8AW93, Q8BMD7, Q8BRB7, Q8BZ21, Q8CAK3, Q8CDN1, Q8HXK7, Q8K3Y6, Q8N2G6, Q8N9V6, Q8TE76

Diamond homologs: A1D3C5, A2A5Z6, A2QQ28, A9JRZ0, B0XQ72, B4F6W9, B8N7E5, C6KTB7, E1B7Q7, F1LP64, F1RCR6, G5E870, O00308, O13834, O14326, O15033, P33202, P40985, Q0CCL1, Q14669, Q15386, Q2TAS2, Q2UBP1, Q4WTF3, Q5BDP1, Q61010, Q6PDK8, Q757T0, Q80U95, Q86UW9, Q86Y01, Q8AW93, Q8BZZ3, Q8C863, Q8CHG5, Q8R3P2, Q96J02, Q9DBH0, Q9H0M0, Q9HAU4

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
DTX1	down-regulates	ASCL1	binding
DTX1	up-regulates	EP300	binding
DTX1	“up-regulates quantity by expression”	ERBB2	“transcriptional regulation”
ITCH	down-regulates	DTX1	ubiquitination
HES1	“down-regulates quantity by repression”	DTX1	“transcriptional regulation”
Ub:E2	“up-regulates activity”	DTX1	ubiquitination
DTX1	down-regulates	TCF3
DTX1	“up-regulates activity”	NOTCH1	ubiquitination
DTX1	“up-regulates activity”	NOTCH	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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
TICAM1, RIP1-mediated IKK complex recruitment	5	200.3×	3e-09
IKK complex recruitment mediated by RIP1	5	165.5×	5e-09
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	5	122.8×	2e-08
Negative regulators of DDX58/IFIH1 signaling	5	108.8×	3e-08
E3 ubiquitin ligases ubiquitinate target proteins	6	77.4×	5e-09
Antigen processing: Ubiquitination & Proteasome degradation	10	24.8×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	7	78.6×	2e-10
protein polyubiquitination	7	53.9×	2e-09
ubiquitin-dependent protein catabolic process	7	34.6×	2e-08
protein ubiquitination	8	22.1×	2e-08
proteasome-mediated ubiquitin-dependent protein catabolic process	6	20.9×	5e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — CLLSLL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	77
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1252006	NC_000012.11:g.113120652_115362584del	Pathogenic

SpliceAI

1204 predictions. Top by Δscore:

Variant	Effect	Δscore
12:113058449:CAGG:C	donor_loss	1.0000
12:113058452:GTGA:G	donor_loss	1.0000
12:113058453:T:G	donor_loss	1.0000
12:113093681:G:GT	donor_gain	1.0000
12:113093684:G:GT	donor_gain	1.0000
12:113093696:AAAGA:A	donor_gain	1.0000
12:113093697:AAGA:A	donor_gain	1.0000
12:113093698:AGA:A	donor_gain	1.0000
12:113093699:GA:G	donor_gain	1.0000
12:113093699:GAG:G	donor_gain	1.0000
12:113093701:G:GG	donor_gain	1.0000
12:113094033:TGCA:T	acceptor_loss	1.0000
12:113094034:GCAG:G	acceptor_loss	1.0000
12:113094035:CA:C	acceptor_loss	1.0000
12:113094097:GAGGT:G	donor_loss	1.0000
12:113094098:AG:A	donor_loss	1.0000
12:113094099:GG:G	donor_loss	1.0000
12:113094100:G:GC	donor_loss	1.0000
12:113094785:GCAGG:G	acceptor_loss	1.0000
12:113094786:CAGGA:C	acceptor_loss	1.0000
12:113094787:A:AG	acceptor_gain	1.0000
12:113094787:A:C	acceptor_loss	1.0000
12:113094787:AG:A	acceptor_gain	1.0000
12:113094788:G:GG	acceptor_gain	1.0000
12:113094788:GG:G	acceptor_gain	1.0000
12:113094788:GGACT:G	acceptor_gain	1.0000
12:113094946:AGGTG:A	donor_gain	1.0000
12:113094948:G:GA	donor_loss	1.0000
12:113095037:CCCA:C	acceptor_loss	1.0000
12:113095040:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000119064 (12:113069922 A>G), RS1000141086 (12:113065181 C>G), RS1000290457 (12:113071275 G>A), RS1000378221 (12:113087454 C>T), RS1000390669 (12:113059053 T>C), RS1000531396 (12:113057187 G>A,T), RS1000543671 (12:113089233 T>C), RS1000547129 (12:113074799 T>C), RS1000600180 (12:113070856 C>T), RS1000704977 (12:113093010 A>C), RS1000756131 (12:113096237 T>A,C,G), RS1000782187 (12:113088781 A>T), RS1000831857 (12:113060304 G>C,T), RS1000897386 (12:113062377 A>G), RS1001010484 (12:113083456 G>T)

Disease associations

OMIM: gene MIM:602582 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001523_11	Visceral adipose tissue adjusted for BMI	1.000000e-06
GCST005329_1	Coffee consumption	2.000000e-16
GCST005951_2	Body mass index	9.000000e-09
GCST90011894_11	Retinitis pigmentosa	8.000000e-06
GCST90020025_104	Waist-to-hip ratio adjusted for BMI	5.000000e-09
GCST90020027_1682	Waist-hip index	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006782	cups of coffee per day measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
pentanal	increases 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	affects cotreatment, decreases expression	1
MRK 003	decreases expression	1
bisphenol S	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Paraquat	affects expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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