ASB2

Summary

ASB2 (ankyrin repeat and SOCS box containing 2, HGNC:16012) is a protein-coding gene on chromosome 14q32.12, encoding Ankyrin repeat and SOCS box protein 2 (Q96Q27). Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

This gene encodes a member of the ankyrin repeat and SOCS box-containing (ASB) protein family. These proteins play a role in protein degradation by coupling suppressor of cytokine signalling (SOCS) proteins with the elongin BC complex. The encoded protein is a subunit of a multimeric E3 ubiquitin ligase complex that mediates the degradation of actin-binding proteins. This gene plays a role in retinoic acid-induced growth inhibition and differentiation of myeloid leukemia cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 51676 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 134 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001202429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16012
Approved symbol	ASB2
Name	ankyrin repeat and SOCS box containing 2
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	ASB-2
Ensembl gene	ENSG00000100628
Ensembl biotype	protein_coding
OMIM	605759
Entrez	51676

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 44 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000315988, ENST00000553883, ENST00000555019, ENST00000555287, ENST00000555374, ENST00000555507, ENST00000556062, ENST00000556337, ENST00000556793, ENST00000557613, ENST00000891200, ENST00000891201, ENST00000891202, ENST00000891203, ENST00000891204, ENST00000891205, ENST00000891206, ENST00000891207, ENST00000891208, ENST00000891209, ENST00000891210, ENST00000891211, ENST00000891212, ENST00000968939, ENST00000968940, ENST00000968941, ENST00000968942, ENST00000968943, ENST00000968944, ENST00000968945, ENST00000968946, ENST00000968947, ENST00000968948, ENST00000968949, ENST00000968950, ENST00000968951, ENST00000968952, ENST00000968953, ENST00000968954, ENST00000968955, ENST00000968956, ENST00000968957, ENST00000968958, ENST00000968959, ENST00000968960, ENST00000968961, ENST00000968962, ENST00000968963

RefSeq mRNA: 2 — MANE Select: NM_001202429 NM_001202429, NM_016150

CCDS: CCDS55940, CCDS9915

Canonical transcript exons

ENST00000555019 — 10 exons

Exon	Start	End
ENSE00000659968	93947349	93947520
ENSE00000659969	93950999	93951244
ENSE00000659970	93953352	93953507
ENSE00000659971	93954317	93954483
ENSE00000941237	93939108	93939672
ENSE00002459114	93934166	93934792
ENSE00002521354	93964334	93964612
ENSE00002534964	93976434	93976570
ENSE00003613753	93937698	93937851
ENSE00003689232	93956766	93956870

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 99.15.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6272 / max 341.0309, expressed in 455 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144665	1.2697	169
144667	0.8754	195
144653	0.7890	164
144659	0.3455	109
144656	0.0882	57
144654	0.0711	43
144668	0.0616	27
144658	0.0529	17
144655	0.0355	24
144666	0.0213	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue	UBERON:0001134	99.15	gold quality
gastrocnemius	UBERON:0001388	99.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.11	gold quality
apex of heart	UBERON:0002098	98.06	gold quality
skeletal muscle organ	UBERON:0014892	97.67	gold quality
muscle of leg	UBERON:0001383	97.61	gold quality
muscle tissue	UBERON:0002385	97.29	gold quality
smooth muscle tissue	UBERON:0001135	96.15	gold quality
heart left ventricle	UBERON:0002084	96.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.78	gold quality
right atrium auricular region	UBERON:0006631	95.22	gold quality
left uterine tube	UBERON:0001303	94.78	gold quality
heart	UBERON:0000948	94.68	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.90	gold quality
lower esophagus	UBERON:0013473	93.84	gold quality
right coronary artery	UBERON:0001625	93.34	gold quality
body of uterus	UBERON:0009853	92.74	gold quality
thoracic aorta	UBERON:0001515	91.82	gold quality
myometrium	UBERON:0001296	91.76	gold quality
ascending aorta	UBERON:0001496	91.74	gold quality
popliteal artery	UBERON:0002250	91.63	gold quality
tibial artery	UBERON:0007610	91.60	gold quality
urinary bladder	UBERON:0001255	91.32	gold quality
descending thoracic aorta	UBERON:0002345	91.28	gold quality
mucosa of stomach	UBERON:0001199	91.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.38	gold quality
colon	UBERON:0001155	89.25	gold quality
fundus of stomach	UBERON:0001160	88.09	gold quality
intestine	UBERON:0000160	87.80	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.25
E-MTAB-4850	no	787.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KMT2A, RARA

miRNA regulators (miRDB)

29 targeting ASB2, 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-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-3180-5P	99.82	69.12	2422
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6796-3P	98.68	65.49	689
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-549A-5P	96.35	68.08	587
HSA-MIR-6828-3P	96.06	67.61	1155

Literature-anchored findings (GeneRIF, showing 11)

• ASB2 may regulate hematopoietic cell differentiation by modulating cell spreading and actin remodeling through targeting of filamins A and B for degradation. (PMID:18799729)
• By shifting monomeric E3 ligase complexes to dimeric forms through activation of Asb2 transcription, Notch could effectively control the turnover of a variety of substrates and it exerts diverse effects on cell proliferation and differentiation. (PMID:21119685)
• ASB2alpha is a novel regulator of integrin-dependent adhesion of hematopoietic cells (PMID:21737450)
• A model whereby ASB2 contributes to hematopoietic differentiation, in part, through MLL degradation and HOX gene down-regulation. (PMID:22174154)
• These results suggest that ASB2beta but not ASB2alpha might be monoubiquitinated and that the ASB2beta UIM motif, but not its E3 Ub ligase activity, plays a pivotal role in this monoubiquitination. (PMID:22382022)
• Data show that neither endogenous nor exogenously expressed ASB2alpha induces degradation of JAK proteins in hematopoietic cells (PMID:22916308)
• Phosphorylation of serine 323 of ASB2 alpha by Erk kinases is critical for ASB2alpha-mediated degradation of FLNA. (PMID:24044920)
• data therefore reveal ubiquitin acceptor sites in FLNa and establish that ASB2alpha-mediated effects on cell spreading are due to loss of filamins. (PMID:24052262)
• Using ASB2 conditional knockout mice. (PMID:26537633)
• functionally relevant miRNA/mRNA interactions were identified in skeletal muscles of myotonic dystrophy type 1 patients, highlighting the dysfunction of miR-29c and ASB2. (PMID:29955039)
• Notch signaling can initiate Asb2 transcription and NF-kappa B activation in T cell acute lymphoblastic leukemia cells. (PMID:30116272)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb2a.1	ENSDARG00000003797
mus_musculus	Asb2	ENSMUSG00000021200
rattus_norvegicus	Asb2	ENSRNOG00000051619

Paralogs (2): ANKRD24 (ENSG00000089847), UACA (ENSG00000137831)

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 2 — Q96Q27 (reviewed: Q96Q27)

All UniProt accessions (5): Q96Q27, G3V2Z2, G3V3P8, G3V484, G3V4B2

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Mediates Notch-induced ubiquitination and degradation of substrates including TCF3/E2A and JAK2. Required during embryonic heart development for complete heart looping. Required for cardiomyocyte differentiation. Specifically promotes the ubiquitination of SMAD9 and targets it for proteasomal degradation, leading to avoid excessive accumulation of SMAD9. Plays a role in the regulation of NK-cell migration by modulating protein levels of filamin A/FLNA via regulation of its ubiquitination and proteasome degradation. Involved in myogenic differentiation and targets filamin FLNB for proteasomal degradation but not filamin FLNA. Also targets DES for proteasomal degradation. Acts as a negative regulator of skeletal muscle mass. Targets filamins FLNA and FLNB for proteasomal degradation. This leads to enhanced adhesion of hematopoietic cells to fibronectin. Required for FLNA degradation in immature cardiomyocytes which is necessary for actin cytoskeleton remodeling, leading to proper organization of myofibrils and function of mature cardiomyocytes. Required for degradation of FLNA and FLNB in immature dendritic cells (DC) which enhances immature DC migration by promoting DC podosome formation and DC-mediated degradation of the extracellular matrix. Does not promote proteasomal degradation of tyrosine-protein kinases JAK1 or JAK2 in hematopoietic cells.

Subunit / interactions. Component of a probable ECS E3 ubiquitin-protein ligase complex which contains CUL5, either RBX1 or RNF7/RBX2, Elongin BC complex (ELOB and ELOC) and ASB2. Interacts with SKP2. Through its interaction with SKP2, likely to bridge the formation of dimeric E3-ubiquitin-protein ligase complexes composed of an ECS complex and an SCF(SKP2) complex. Interacts with JAK2; the interaction targets JAK2 for Notch-mediated proteasomal degradation. Interacts with TCF3/E2A; the interaction is mediated by SKP2 and targets TCF3 for Notch-mediated proteasomal degradation. Interacts with DES.

Subcellular location. Cytoplasm. Cytoskeleton. Stress fiber Cytoplasm. Myofibril. Sarcomere. Z line.

Tissue specificity. Expressed in muscle cells. Expressed in hematopoietic cells.

Post-translational modifications. Monoubiquitinated. Not monoubiquitinated. Phosphorylation at Ser-371 is required for association with FLNA and subsequent FLNA degradation.

Domain organisation. The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. Both the N-terminus and ANK repeats 1 to 10 are necessary for interaction with filamins. The UIM domain is required for monoubiquitination.

Induction. Induced by all-trans retinoic acid (ATRA). Induced by Notch signaling. Repressed by microRNA miR-29c.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ankyrin SOCS box (ASB) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96Q27-2	1, ASB2beta, muscle-type	yes
Q96Q27-1	2, ASB2alpha, hematopoietic-type

RefSeq proteins (2): NP_001189358, NP_057234 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001496	SOCS_box	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR036036	SOCS_box-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037330	ASB2_SOCS	Domain

Pfam: PF07525, PF12796, PF13606, PF13637

UniProt features (29 total): repeat 12, mutagenesis site 8, domain 2, sequence conflict 2, chain 1, modified residue 1, splice variant 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q27-F1	83.96	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 371

Mutagenesis-validated functional residues (8):

Position	Phenotype
27–29	abolishes monoubiquitination.
38	abolishes monoubiquitination.
371	abolishes phosphorylation. abolishes degradation of flna. no effect on assembly into ubiquitin-protein ligase complex.
371	phosphomimetic mutant. no effect on isoform 2 flna degradation. no effect on assembly into ubiquitin-protein ligase comp
596	no interaction with elongin bc complex.
599–600	no interaction with cul5 or rnf7.
600	no interaction with elongin bc complex.
619–622	no interaction with cul5 or rnf7.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 268 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_DENDRITIC_CELL_MIGRATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_SKELETAL_MUSCLE_ADAPTATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION

GO Biological Process (14): heart looping (GO:0001947), ubiquitin-dependent protein catabolic process (GO:0006511), signal transduction (GO:0007165), skeletal muscle atrophy (GO:0014732), protein ubiquitination (GO:0016567), actin cytoskeleton organization (GO:0030036), intracellular signal transduction (GO:0035556), skeletal muscle cell differentiation (GO:0035914), dendritic cell migration (GO:0036336), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), cardiac muscle cell differentiation (GO:0055007), cardiac muscle cell development (GO:0055013), podosome assembly (GO:0071800), regulation of barbed-end actin filament capping (GO:2000812)

GO Molecular Function (3): cullin family protein binding (GO:0097602), protein binding (GO:0005515), ubiquitin protein ligase activity (GO:0061630)

GO Cellular Component (7): ubiquitin ligase complex (GO:0000151), stress fiber (GO:0001725), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), Z disc (GO:0030018), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
striated muscle atrophy	1
skeletal muscle adaptation	1
protein modification by small protein conjugation	1
cytoskeleton organization	1
actin filament-based process	1
signal transduction	1
skeletal muscle tissue development	1
cell differentiation	1
mononuclear cell migration	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cardiocyte differentiation	1
cardiac muscle tissue development	1
striated muscle cell differentiation	1
striated muscle cell development	1
cardiac cell development	1
cardiac muscle cell differentiation	1
protein-containing complex assembly	1
plasma membrane bounded cell projection assembly	1
regulation of actin filament polymerization	1
regulation of actin filament depolymerization	1
barbed-end actin filament capping	1
protein binding	1
binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
intracellular protein-containing complex	1
transferase complex	1
actomyosin	1

Protein interactions and networks

STRING

1700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB2	CUL5	Q93034	873
ASB2	ASB17	Q8WXJ9	864
ASB2	RNF7	Q9UBF6	813
ASB2	CISH	Q9NSE2	811
ASB2	FTO	Q9C0B1	657
ASB2	RARA	P10276	650
ASB2	ALKBH5	Q6P6C2	593
ASB2	METTL3	Q86U44	586
ASB2	METTL14	Q9HCE5	586
ASB2	JAK3	P52333	584
ASB2	TGM6	O95932	583
ASB2	YTHDF2	Q9Y5A9	571
ASB2	ADAM8	P78325	543
ASB2	ANK1	P16157	538
ASB2	ANK3	Q12955	537

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PRKN	ASB2	psi-mi:“MI:0915”(physical association)	0.490
ASB2	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
ESR2		psi-mi:“MI:0914”(association)	0.350
ASB2	NFKB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): UBC (Biochemical Activity), UBC (Biochemical Activity), FLNA (Biochemical Activity), ASB2 (Biochemical Activity), DCUN1D3 (Affinity Capture-MS), CUL5 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), ASB2 (PCA), NFKBIA (Affinity Capture-Western), ASB2 (Affinity Capture-RNA), ASB2 (Proximity Label-MS), CUL5 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), DCUN1D3 (Affinity Capture-MS), ASB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A2AGL3, A7MB89, B0LPN4, E9Q401, O60733, P30957, P42694, P49754, P97570, P97819, Q15413, Q29RM5, Q2KIX2, Q2T9K6, Q32PW3, Q3SX45, Q4V890, Q59H18, Q5F361, Q5GIG6, Q5KU39, Q5RF15, Q5U2S6, Q5ZKK2, Q66H07, Q66H63, Q6B858, Q6DFV5, Q6NYU2, Q7T3P8, Q7TQP6, Q8C0T1, Q8CEF1, Q8K0L0, Q8K114, Q8TC84, Q91W86, Q92736

Diamond homologs: A2RUV0, A6NK59, O35516, P0C927, Q04721, Q3SX45, Q58CT0, Q5U2S6, Q8C6Y6, Q8HXA6, Q8K0L0, Q8VHS6, Q8WXK1, Q96Q27, Q9QW30, A1Z6E0, A8QGZ7, A8XT88, B0X9V1, B3MDR0, B3NRP1, B4F739, B4GBN7, B4HQ29, B4J6Q0, B4KNC5, B4LMQ3, B4MR59, B4P4K8, B4QE02, O88838, P0C2W1, P0CH38, Q16XV7, Q18223, Q290L5, Q5E9X6, Q5M877, Q6NZ03, Q7QGL9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ASB2	“down-regulates quantity by destabilization”	FLNA	polyubiquitination
ASB2	“up-regulates activity”	“Elongin E3-Cul-5”	binding
ASB2	“down-regulates quantity by destabilization”	FLNB	binding
ERK1/2	“up-regulates activity”	ASB2	phosphorylation
MAPK1	“up-regulates activity”	ASB2	phosphorylation
MAPK3	“up-regulates activity”	ASB2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	120
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1527831	GRCh37/hg19 14q31.3-32.13(chr14:88345625-94773741)	Pathogenic
2570894	GRCh37/hg19 14q31.3-32.13(chr14:88401076-94725706)x1	Pathogenic
57811	GRCh38/hg38 14q32.11-32.13(chr14:90255156-95274696)x1	Pathogenic
1348382	NC_000014.8:g.(?93687728)(95560403_?)del	Likely pathogenic

SpliceAI

1573 predictions. Top by Δscore:

Variant	Effect	Δscore
14:93937692:CCCTA:C	donor_loss	1.0000
14:93937693:CCTA:C	donor_loss	1.0000
14:93937694:CTACC:C	donor_loss	1.0000
14:93937695:TA:T	donor_loss	1.0000
14:93937697:CCTG:C	donor_gain	1.0000
14:93937847:CAGAA:C	acceptor_gain	1.0000
14:93937849:GAA:G	acceptor_gain	1.0000
14:93937850:AA:A	acceptor_gain	1.0000
14:93937851:ACTGA:A	acceptor_loss	1.0000
14:93937852:C:CC	acceptor_gain	1.0000
14:93937852:CTGAA:C	acceptor_loss	1.0000
14:93947343:GCTGA:G	donor_loss	1.0000
14:93947344:CTGAC:C	donor_loss	1.0000
14:93947345:TGAC:T	donor_loss	1.0000
14:93947346:GAC:G	donor_loss	1.0000
14:93947347:A:C	donor_loss	1.0000
14:93947348:C:CG	donor_loss	1.0000
14:93947394:T:TA	donor_gain	1.0000
14:93947516:AGCAC:A	acceptor_gain	1.0000
14:93947517:GCAC:G	acceptor_gain	1.0000
14:93947518:CAC:C	acceptor_gain	1.0000
14:93947518:CACC:C	acceptor_gain	1.0000
14:93947519:AC:A	acceptor_gain	1.0000
14:93947520:CC:C	acceptor_gain	1.0000
14:93947521:C:CA	acceptor_loss	1.0000
14:93947521:C:CC	acceptor_gain	1.0000
14:93950998:CCGTA:C	donor_gain	1.0000
14:93951002:A:AC	donor_gain	1.0000
14:93951003:C:CC	donor_gain	1.0000
14:93951252:C:CT	acceptor_gain	1.0000

AlphaMissense

4147 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:93937759:G:C	C522W	0.999
14:93937761:A:G	C522R	0.999
14:93937760:C:T	C522Y	0.998
14:93939494:G:T	R363S	0.998
14:93947470:C:G	A263P	0.998
14:93951046:G:T	A230D	0.998
14:93951157:G:T	A193D	0.998
14:93937847:C:T	C493Y	0.997
14:93937848:A:G	C493R	0.997
14:93947382:G:C	P292R	0.997
14:93947433:A:G	L275P	0.997
14:93947465:G:C	C264W	0.997
14:93947478:A:T	L260H	0.997
14:93951043:G:T	A231D	0.997
14:93951075:G:C	N220K	0.997
14:93951075:G:T	N220K	0.997
14:93951240:G:C	C165W	0.997
14:93951241:C:T	C165Y	0.997
14:93937722:A:G	W535R	0.996
14:93937722:A:T	W535R	0.996
14:93937787:A:G	L513P	0.996
14:93937846:A:C	C493W	0.996
14:93939207:G:C	F458L	0.996
14:93939207:G:T	F458L	0.996
14:93939208:A:G	F458S	0.996
14:93939209:A:G	F458L	0.996
14:93939500:C:G	D361H	0.996
14:93939595:G:T	A329D	0.996
14:93939596:C:G	A329P	0.996
14:93939612:A:C	S323R	0.996

dbSNP variants (sampled 300 via entrez): RS1000018661 (14:93966398 G>C), RS1000030441 (14:93959910 C>A,T), RS1000159675 (14:93965190 A>G), RS1000218839 (14:93956244 T>A), RS1000250185 (14:93955668 G>A), RS1000334789 (14:93935274 A>G), RS1000551754 (14:93935207 A>G), RS1000618969 (14:93975688 C>T), RS1000677224 (14:93965478 C>A,G), RS1000741705 (14:93946435 G>T), RS1000853992 (14:93935497 G>A), RS1000887689 (14:93965424 A>G), RS1000899825 (14:93964010 C>T), RS1000937531 (14:93939609 C>A,T), RS1001023202 (14:93965083 C>G,T)

Disease associations

OMIM: gene MIM:605759 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): DICER1-related tumor predisposition (MONDO:0100216)

Orphanet (1): DICER1 tumor-predisposition syndrome (Orphanet:284343)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003030_7	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	5.000000e-06
GCST004600_22	Eosinophil percentage of white cells	5.000000e-19
GCST004606_81	Eosinophil count	1.000000e-20
GCST004617_154	Eosinophil percentage of granulocytes	9.000000e-17
GCST004623_69	Neutrophil percentage of granulocytes	1.000000e-15
GCST004624_157	Sum eosinophil basophil counts	4.000000e-20
GCST90002381_608	Eosinophil count	1.000000e-38
GCST90002381_609	Eosinophil count	8.000000e-26
GCST90002382_230	Eosinophil percentage of white cells	2.000000e-37
GCST90002382_231	Eosinophil percentage of white cells	4.000000e-27
GCST90011899_20	Aspartate aminotransferase levels	4.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007679	oppositional defiant disorder measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects reaction, increases expression, affects methylation, increases methylation	8
Tetrachlorodibenzodioxin	increases expression	4
Valproic Acid	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
tungsten carbide	affects binding, increases expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	increases expression	1
trimellitic anhydride	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Air Pollutants	affects expression, increases abundance	1
Aldehydes	increases expression	1
Azacitidine	increases expression	1
Bleomycin	decreases expression	1
Cisplatin	increases expression	1
Cobalt	affects binding, increases expression	1
Diuron	decreases expression	1
Doxorubicin	affects expression	1
Lead	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03382158	Not specified	RECRUITING	International PPB/DICER1 Registry
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients