DIDO1

Summary

DIDO1 (death inducer-obliterator 1, HGNC:2680) is a protein-coding gene on chromosome 20q13.33, encoding Death-inducer obliterator 1 (Q9BTC0). Putative transcription factor, weakly pro-apoptotic when overexpressed. It is a selective cancer dependency (DepMap: 28.6% of cell lines).

Apoptosis, a major form of cell death, is an efficient mechanism for eliminating unwanted cells and is of central importance for development and homeostasis in metazoan animals. In mice, the death inducer-obliterator-1 gene is upregulated by apoptotic signals and encodes a cytoplasmic protein that translocates to the nucleus upon apoptotic signal activation. When overexpressed, the mouse protein induced apoptosis in cell lines growing in vitro. This gene is similar to the mouse gene and therefore is thought to be involved in apoptosis. Alternatively spliced transcripts have been found for this gene, encoding multiple isoforms.

Source: NCBI Gene 11083 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thyroid hormone metabolism, abnormal, 2 (Moderate, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 262 total — 2 pathogenic
• Cancer dependency (DepMap): dependent in 28.6% of screened cell lines
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_001193369

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2680
Approved symbol	DIDO1
Name	death inducer-obliterator 1
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	DIO1, dJ885L7.8, FLJ11265, KIAA0333, DIO-1, BYE1
Ensembl gene	ENSG00000101191
Ensembl biotype	protein_coding
OMIM	604140
Entrez	11083

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000266070, ENST00000354665, ENST00000370366, ENST00000370368, ENST00000370371, ENST00000395340, ENST00000395343, ENST00000933083, ENST00000933084, ENST00000933085, ENST00000933086

RefSeq mRNA: 6 — MANE Select: NM_001193369 NM_001193369, NM_001193370, NM_022105, NM_033081, NM_080796, NM_080797

CCDS: CCDS13508, CCDS13509, CCDS33506

Canonical transcript exons

ENST00000395343 — 16 exons

Exon	Start	End
ENSE00000663338	62893666	62894194
ENSE00000663339	62894413	62894548
ENSE00000663342	62907147	62907359
ENSE00000856524	62891987	62892076
ENSE00000856527	62895049	62895165
ENSE00000856528	62896233	62896392
ENSE00000856529	62896531	62896996
ENSE00000856530	62905887	62906100
ENSE00000856534	62909699	62910020
ENSE00001109189	62892809	62892962
ENSE00001174744	62890960	62891155
ENSE00001177957	62914210	62914406
ENSE00001337044	62910774	62911614
ENSE00001521414	62877743	62882414
ENSE00002988125	62894810	62894914
ENSE00003897598	62926439	62926505

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 94.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.5269 / max 279.7789, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188310	20.9572	1810
188311	13.3914	1768
188312	1.6285	858
188308	0.5498	301

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.76	silver quality
sural nerve	UBERON:0015488	93.91	gold quality
right uterine tube	UBERON:0001302	93.40	gold quality
tendon of biceps brachii	UBERON:0008188	93.15	gold quality
tendon	UBERON:0000043	93.00	gold quality
body of uterus	UBERON:0009853	92.32	gold quality
calcaneal tendon	UBERON:0003701	92.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.22	gold quality
left ovary	UBERON:0002119	92.09	gold quality
popliteal artery	UBERON:0002250	91.99	gold quality
tibial artery	UBERON:0007610	91.99	gold quality
medial globus pallidus	UBERON:0002477	91.90	gold quality
right coronary artery	UBERON:0001625	91.86	gold quality
descending thoracic aorta	UBERON:0002345	91.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.66	gold quality
aorta	UBERON:0000947	91.64	gold quality
skin of leg	UBERON:0001511	91.64	gold quality
apex of heart	UBERON:0002098	91.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.34	gold quality
lower esophagus	UBERON:0013473	91.33	gold quality
left uterine tube	UBERON:0001303	91.28	gold quality
right ovary	UBERON:0002118	91.27	gold quality
thoracic aorta	UBERON:0001515	91.26	gold quality
ascending aorta	UBERON:0001496	91.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.19	gold quality
mucosa of stomach	UBERON:0001199	91.16	gold quality
skin of abdomen	UBERON:0001416	91.16	gold quality
tibial nerve	UBERON:0001323	91.09	gold quality
ovary	UBERON:0000992	90.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94
E-MTAB-10290	no	90.77

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
ACHE
CAT
CCND3
CREBBP
DIDO1
FTMT
ITGA5	Activation
ITGAV
MITF
PDC
RB1
RBL2
SGCA
TNF

Upstream regulators (CollecTRI, top): AP1, DIDO1, JUN, TP53

miRNA regulators (miRDB)

51 targeting DIDO1, 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-188-3P	100.00	68.76	1240
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-1273H-3P	99.29	67.55	980

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• Novel transcription factors identified in human CD34 antigen-positive hematopoietic stem cells. (PMID:12070015)
• Data suggest that Dido might be one of the tumor suppressor genes at chromosome 20q and that the Dido-targeted mouse may be a suitable model for studying myeloproliferative diseases and myelodysplastic syndromes. (PMID:16127461)
• Dido3, the largest splice variant of the Dido gene, is a centrosome-associated protein whose disruption leads to supernumerary centrosomes, failure to maintain cellular mitotic arrest, and early degradation of the mitotic checkpoint protein BubR1. (PMID:17299043)
• Gambogic acid induces DIDO1-mediated apoptosis in Jurkat T cells. (PMID:18298900)
• Gambogic acid induces the apoptosis of Raji cells through DIO-1 upregulation, nuclear translocation, Bcl-xL downregulation and caspase 3 activation. (PMID:19236754)
• Dido1 induces the expression of Integrin alphaV, thereby promoting the attachment, migration, invasion and apoptosis resistance of melanoma cells. (PMID:22469980)
• Data show that CSE1L, DIDO1 and RBM39 mRNA expression levels correlated with chromosome 20q DNA copy number status. (PMID:22711543)
• evaluated the Death Inducer-Obliterator (DIDO) (variants DIDO 1, 2 and 3) levels in CML, PV, ET and PMF patients. Our data reported the DIDO 1, 2 and 3 differential expressions in Myeloproliferative Neoplasms. (PMID:27282563)
• Results identified a novel pH-dependent mechanism by which epigenetic reader, the PHD fingers of DIDO, recognize the histone mark H3K4me3. The pH-sensing ability might be necessary for normal biological processes and those characterized by altered cellular pH. (PMID:28919441)
• Role of DIDO1 in Progression of Esophageal Squamous Cell Carcinoma. (PMID:30761474)
• Dido3 is an adaptor that controls SFPQ utilization in RNA splicing (PMID:30931476)
• CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability. (PMID:34384442)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-181d5.4	ENSDARG00000057907
mus_musculus	Dido1	ENSMUSG00000038914
rattus_norvegicus	Dido1	ENSRNOG00000009936

Paralogs (2): PHF3 (ENSG00000118482), SPOCD1 (ENSG00000134668)

Protein

Protein identifiers

Death-inducer obliterator 1 — Q9BTC0 (reviewed: Q9BTC0)

Alternative names: Death-associated transcription factor 1

All UniProt accessions (1): Q9BTC0

UniProt curated annotations — full annotation on UniProt →

Function. Putative transcription factor, weakly pro-apoptotic when overexpressed. Tumor suppressor. Required for early embryonic stem cell development. Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes.

Subunit / interactions. Interacts specifically (via PHD-type zinc finger) with histone H3 that is trimethylated at ‘Lys-4’ (H3K4me3), histone phosphorylation at ‘Thr-3’ or ‘Thr-6’ disrupts this binding and promotes translocation of DIDO1 from chromatin to the mitotic spindle during mitosis.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Spindle.

Tissue specificity. Ubiquitous.

Domain organisation. The PHD-type zinc finger forms an aromatic cage around H3K4me3.

Miscellaneous. Defects in DIDO1 may be a cause of myeloid neoplasms.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BTC0-4	4, DIDO3	yes
Q9BTC0-1	1, DIDO2
Q9BTC0-2	2, DIDO1
Q9BTC0-3	3, a

RefSeq proteins (6): NP_001180298, NP_001180299, NP_071388, NP_149072, NP_542986, NP_542987 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR003618	TFIIS_cen_dom	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR012921	SPOC_C	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR033082	DIDO1_PHD	Domain
IPR036575	TFIIS_cen_dom_sf	Homologous_superfamily

Pfam: PF00628, PF07500, PF07744

UniProt features (96 total): modified residue 30, compositionally biased region 25, region of interest 10, sequence variant 7, splice variant 6, turn 3, strand 3, short sequence motif 2, cross-link 2, sequence conflict 2, helix 2, chain 1, domain 1, zinc finger region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4L7X	X-RAY DIFFRACTION	1.35
2M3H	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTC0-F1	46.89	0.08

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 (32): 1, 60, 114, 151, 152, 154, 523, 805, 809, 889, 898, 1019, 1030, 1040, 1244, 1256, 1260, 1312, 1456, 1469 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
291	abolishes binding to h3k4me3.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis

MSigDB gene sets: 338 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_93, MODULE_516, WANG_CLIM2_TARGETS_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_MEIOTIC_SYNAPSIS, CMYB_01, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, MODULE_445, MENSE_HYPOXIA_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, AAAYRNCTG_UNKNOWN

GO Biological Process (4): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), apoptotic signaling pathway (GO:0097190), apoptotic process (GO:0006915)

GO Molecular Function (4): RNA binding (GO:0003723), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856), Set1C/COMPASS complex (GO:0048188)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Meiosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
gene expression	1
RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
apoptotic process	1
signal transduction	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule cytoskeleton	1
histone methyltransferase complex	1

Protein interactions and networks

STRING

2797 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIDO1	BUB1B	O60566	594
DIDO1	ING3	Q9NXR8	589
DIDO1	BTBD7	Q9P203	581
DIDO1	H3C1	P02295	523
DIDO1	H3-3A	P06351	522
DIDO1	H3-4	Q16695	514
DIDO1	H3-7	Q5TEC6	514
DIDO1	H3-5	Q6NXT2	514
DIDO1	H3C14	Q71DI3	514
DIDO1	TAF3	Q5VWG9	513
DIDO1	TCEA2	Q15560	479
DIDO1	KDM7A	Q6ZMT4	469
DIDO1	GTF3C2	Q8WUA4	450
DIDO1	TCEA1	P23193	447
DIDO1	SEC31A	O94979	440

IntAct

129 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
KHDRBS2	KHDRBS3	psi-mi:“MI:0914”(association)	0.800
DIDO1	OGT	psi-mi:“MI:0914”(association)	0.670
OGT	DIDO1	psi-mi:“MI:0915”(physical association)	0.670
PIN1	POLR2D	psi-mi:“MI:0914”(association)	0.640
DIDO1	HCFC1	psi-mi:“MI:0915”(physical association)	0.560
HCFC2	SETD1A	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
KLHDC3	CLUH	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
SRSF1	DIDO1	psi-mi:“MI:0915”(physical association)	0.520
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
DIDO1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
	DIDO1	psi-mi:“MI:0407”(direct interaction)	0.440
TNKS2	DIDO1	psi-mi:“MI:0407”(direct interaction)	0.440
PARP2	DIDO1	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
Dlg4	DIDO1	psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
CDKN2A	DIDO1	psi-mi:“MI:0915”(physical association)	0.400
DIDO1		psi-mi:“MI:0915”(physical association)	0.370
ARAF	DIDO1	psi-mi:“MI:0915”(physical association)	0.370
DIDO1	KCNK4	psi-mi:“MI:0915”(physical association)	0.370
DVL3	DIDO1	psi-mi:“MI:0915”(physical association)	0.370
HNRNPK	DIDO1	psi-mi:“MI:0915”(physical association)	0.370
WWP2	DIDO1	psi-mi:“MI:0915”(physical association)	0.370
WWP1	DIDO1	psi-mi:“MI:0915”(physical association)	0.370
Srp72		psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (229): DIDO1 (Protein-peptide), DIDO1 (Affinity Capture-MS), DIDO1 (Affinity Capture-MS), DIDO1 (Affinity Capture-MS), RBM15 (Co-fractionation), DIDO1 (Synthetic Lethality), DIDO1 (Biochemical Activity), DIDO1 (Affinity Capture-MS), DIDO1 (Synthetic Lethality), DIDO1 (Affinity Capture-MS), DIDO1 (Two-hybrid), DIDO1 (Two-hybrid), DIDO1 (Two-hybrid), DIDO1 (Two-hybrid), DIDO1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTU1, A2AUY4, B7ZS37, D3Z8Y2, D4A4L4, D4A666, E1B7L7, O46385, O60293, O75152, O95425, P0DQW0, Q08AZ1, Q3KQW7, Q3U1C4, Q3UH68, Q3ZC82, Q4G0F8, Q4V9H5, Q5F3Z9, Q5NBX1, Q5REG6, Q5ZJJ1, Q5ZM88, Q61464, Q62394, Q68FE9, Q6NZF1, Q6PJT7, Q6ZQ03, Q6ZU65, Q76L83, Q7TMD5, Q8BHZ4, Q8BJ05, Q8BLG0, Q8BZ32, Q8C9B9, Q8CCJ9, Q8K298

Diamond homologs: A2WXR5, A2XTW9, A2Y0Q2, A2Y4R8, B8ADZ3, B8AMA8, B8B8C5, B8B8I3, B8BJV8, O74508, O81488, Q12830, Q2R837, Q40359, Q5EA28, Q5XEM9, Q60DW3, Q6BER5, Q6YTY3, Q6Z7F4, Q75IR6, Q7F2Z1, Q7XUW3, Q80TJ7, Q84TV4, Q8C9B9, Q8H383, Q8LA16, Q8S8M9, Q9BTC0, Q9CWW7, Q9FFF5, Q9M2B4, Q9P0U4, Q9SRM4, Q9UPP1, Q9W0T1, Q9W352, P0CF52, P0CH95

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DIDO1	“up-regulates quantity by expression”	ITGA5	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
mRNA Splicing	16	14.5×	2e-12
Processing of Capped Intron-Containing Pre-mRNA	19	12.9×	1e-13
mRNA Polyadenylation	17	12.3×	3e-12
mRNA 3’-end processing	7	11.4×	2e-04
mRNA Splicing - Minor Pathway	6	11.1×	1e-03
RNA Polymerase II Transcription Termination	6	10.9×	1e-03
mRNA Splicing - Major Pathway	22	9.9×	1e-13
Dengue Virus-Host Interactions	23	8.7×	3e-13

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mRNA splicing, via spliceosome	5	28.8×	1e-04
regulation of alternative mRNA splicing, via spliceosome	8	12.7×	6e-05
mRNA splicing, via spliceosome	18	10.7×	9e-11
RNA processing	7	9.9×	9e-04
RNA splicing	17	9.7×	1e-09
negative regulation of translation	7	8.9×	2e-03
mRNA processing	17	8.7×	4e-09
chromatin remodeling	12	5.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	185
Likely benign	28
Benign	11

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1686838	NM_000792.7(DIO1):c.282C>A (p.Asn94Lys)	Pathogenic
1686839	NM_000792.7(DIO1):c.603G>A (p.Met201Ile)	Pathogenic

SpliceAI

3697 predictions. Top by Δscore:

Variant	Effect	Δscore
1:53906274:G:GT	donor_gain	1.0000
1:53906275:A:T	donor_gain	1.0000
20:62890954:GCTTA:G	donor_loss	1.0000
20:62890958:A:AG	donor_loss	1.0000
20:62892884:AAAT:A	donor_gain	1.0000
20:62892887:T:TA	donor_gain	1.0000
20:62892892:T:A	donor_gain	1.0000
20:62894190:CTGGC:C	acceptor_gain	1.0000
20:62894544:TGTTC:T	acceptor_gain	1.0000
20:62894545:GTTC:G	acceptor_gain	1.0000
20:62894546:TTC:T	acceptor_gain	1.0000
20:62894547:TC:T	acceptor_gain	1.0000
20:62894548:CC:C	acceptor_gain	1.0000
20:62894549:C:CC	acceptor_gain	1.0000
20:62894549:C:T	acceptor_gain	1.0000
20:62894805:CTTA:C	donor_loss	1.0000
20:62894806:TTACC:T	donor_loss	1.0000
20:62894807:TACC:T	donor_loss	1.0000
20:62894808:A:AC	donor_gain	1.0000
20:62894808:AC:A	donor_gain	1.0000
20:62894808:ACCT:A	donor_gain	1.0000
20:62894809:C:CC	donor_gain	1.0000
20:62894809:CC:C	donor_gain	1.0000
20:62894809:CCT:C	donor_gain	1.0000
20:62894809:CCTC:C	donor_gain	1.0000
20:62894809:CCTCT:C	donor_gain	1.0000
20:62894910:ATCAC:A	acceptor_gain	1.0000
20:62894911:TCAC:T	acceptor_gain	1.0000
20:62894912:CAC:C	acceptor_gain	1.0000
20:62894912:CACC:C	acceptor_gain	1.0000

AlphaMissense

14552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62882381:C:T	G1192E	1.000
20:62882382:C:A	G1192W	1.000
20:62882382:C:G	G1192R	1.000
20:62882382:C:T	G1192R	1.000
20:62891019:A:G	L1161P	1.000
20:62891023:A:C	Y1160D	1.000
20:62891025:A:G	L1159P	1.000
20:62891028:T:A	D1158V	1.000
20:62891028:T:C	D1158G	1.000
20:62891028:T:G	D1158A	1.000
20:62891029:C:G	D1158H	1.000
20:62891058:A:T	V1148D	1.000
20:62891061:C:T	G1147D	1.000
20:62891062:C:G	G1147R	1.000
20:62891094:A:G	L1136P	1.000
20:62891136:A:G	F1122S	1.000
20:62891139:C:G	R1121P	1.000
20:62891987:C:A	K1115N	1.000
20:62891987:C:G	K1115N	1.000
20:62892019:A:G	Y1105H	1.000
20:62892025:A:G	W1103R	1.000
20:62892025:A:T	W1103R	1.000
20:62892027:A:T	V1102D	1.000
20:62892048:C:T	G1095E	1.000
20:62892060:A:T	I1091N	1.000
20:62892837:A:T	V1076D	1.000
20:62892858:A:G	F1069S	1.000
20:62892888:C:T	G1059E	1.000
20:62892889:C:G	G1059R	1.000
20:62892889:C:T	G1059R	1.000

dbSNP variants (sampled 300 via entrez): RS1000017755 (20:62916444 T>C), RS1000026508 (20:62897815 G>A), RS1000082404 (20:62902186 C>A,T), RS1000085881 (20:62937224 G>A,C), RS1000096163 (20:62898883 C>T), RS1000150377 (20:62938526 G>A), RS1000178590 (20:62901929 A>G), RS1000244659 (20:62906805 C>T), RS1000361695 (20:62911976 G>A), RS1000379138 (20:62898017 G>A), RS1000389526 (20:62908822 G>A,C), RS1000392531 (20:62932199 G>A), RS1000532222 (20:62900944 G>C), RS1000612406 (20:62883183 CA>C), RS1000685866 (20:62930214 C>A)

Disease associations

OMIM: gene MIM:604140 | disease phenotypes: MIM:619855

GenCC curated gene-disease

Disease	Classification	Inheritance
thyroid hormone metabolism, abnormal, 2	Moderate	Autosomal dominant

Mondo (1): thyroid hormone metabolism, abnormal, 2 (MONDO:0030839)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001856_10	Thyroid hormone levels	3.000000e-18
GCST001856_11	Thyroid hormone levels	5.000000e-15
GCST001856_22	Thyroid hormone levels	8.000000e-32
GCST005312_19	Menopause (age at onset)	2.000000e-10
GCST005312_46	Menopause (age at onset)	6.000000e-10
GCST008164_1	Free thyroxine concentration	5.000000e-34
GCST012353_10	Serum metabolite concentrations in chronic kidney disease	1.000000e-10
GCST90002392_117	Mean corpuscular volume	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0004704	age at menopause

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
methylmercuric chloride	increases expression	2
trichostatin A	affects expression, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Indomethacin	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
titanium dioxide	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	increases phosphorylation	1
pentanal	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW18	K562 eGFP-DIDO1	Cancer cell line	Female

Clinical trials (associated diseases)

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