TTC3

Summary

TTC3 (tetratricopeptide repeat domain 3, HGNC:12393) is a protein-coding gene on chromosome 21q22.13, encoding E3 ubiquitin-protein ligase TTC3 (P53804). E3 ubiquitin-protein ligase which catalyzes the formation of ‘Lys-48’-polyubiquitin chains.

Enables ubiquitin-protein transferase activity. Involved in protein K48-linked ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleolus; and nucleoplasm.

Source: NCBI Gene 7267 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 357 total
• MANE Select transcript: NM_001330683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12393
Approved symbol	TTC3
Name	tetratricopeptide repeat domain 3
Location	21q22.13
Locus type	gene with protein product
Status	Approved
Aliases	TPRD, TPRDI, DCRR1, TPRDII, TPRDIII, RNF105
Ensembl gene	ENSG00000182670
Ensembl biotype	protein_coding
OMIM	602259
Entrez	7267

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 14 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000354749, ENST00000399010, ENST00000399017, ENST00000411496, ENST00000414818, ENST00000418766, ENST00000428693, ENST00000438055, ENST00000450533, ENST00000460328, ENST00000463216, ENST00000469939, ENST00000472398, ENST00000476784, ENST00000479930, ENST00000481605, ENST00000484047, ENST00000485402, ENST00000487711, ENST00000488522, ENST00000491952, ENST00000492275, ENST00000494243, ENST00000540756, ENST00000696811, ENST00000696812

RefSeq mRNA: 10 — MANE Select: NM_001330683 NM_001001894, NM_001320703, NM_001320704, NM_001330681, NM_001330682, NM_001330683, NM_001353936, NM_001353937, NM_001353938, NM_003316

CCDS: CCDS13651, CCDS93095, CCDS93096

Canonical transcript exons

ENST00000418766 — 46 exons

Exon	Start	End
ENSE00001635826	37073254	37073473
ENSE00001867322	37135380	37135514
ENSE00003465554	37121817	37121979
ENSE00003482158	37094005	37094090
ENSE00003489082	37122983	37123028
ENSE00003496994	37126080	37126143
ENSE00003506193	37124619	37124742
ENSE00003507071	37091293	37091413
ENSE00003552849	37132682	37132766
ENSE00003565200	37096581	37096643
ENSE00003608391	37129003	37129063
ENSE00003608941	37095350	37095444
ENSE00003612884	37088196	37088346
ENSE00003637056	37108392	37108446
ENSE00003656402	37087833	37087875
ENSE00003656477	37088799	37088886
ENSE00003656604	37087247	37087401
ENSE00003675922	37090233	37090286
ENSE00003968496	37192112	37192213
ENSE00003968497	37140561	37140673
ENSE00003968499	37152951	37153277
ENSE00003968500	37160802	37160858
ENSE00003968501	37151893	37152029
ENSE00003968504	37195675	37196036
ENSE00003968508	37150078	37150170
ENSE00003968512	37161990	37162063
ENSE00003968513	37172595	37172744
ENSE00003968515	37188495	37188595
ENSE00003968516	37165550	37166615
ENSE00003968518	37201440	37203107
ENSE00003968519	37197570	37197696
ENSE00003968520	37159699	37159745
ENSE00003968522	37167555	37167620
ENSE00003968523	37164051	37164215
ENSE00003968524	37147481	37147603
ENSE00003968526	37200232	37200324
ENSE00003968528	37185706	37185774
ENSE00003968529	37197882	37198025
ENSE00003968532	37156655	37156906
ENSE00003968533	37182774	37182913
ENSE00003968534	37187049	37187145
ENSE00003968535	37144525	37144645
ENSE00003968536	37138634	37138714
ENSE00003968537	37191334	37191424
ENSE00003968538	37148546	37148647
ENSE00003968539	37150820	37150884

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.3329 / max 760.7416, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189014	50.2849	1818
189013	5.5363	1600
189020	0.9022	308
209310	0.4077	214
189015	0.2019	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.44	gold quality
entorhinal cortex	UBERON:0002728	99.42	gold quality
middle temporal gyrus	UBERON:0002771	99.40	gold quality
tibia	UBERON:0000979	99.38	gold quality
postcentral gyrus	UBERON:0002581	99.34	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.34	gold quality
parietal lobe	UBERON:0001872	99.27	gold quality
lateral globus pallidus	UBERON:0002476	99.26	gold quality
substantia nigra pars compacta	UBERON:0001965	99.24	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.24	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.22	gold quality
corpus epididymis	UBERON:0004359	99.16	gold quality
ganglionic eminence	UBERON:0004023	99.14	gold quality
pylorus	UBERON:0001166	99.08	gold quality
pigmented layer of retina	UBERON:0001782	99.08	gold quality
endothelial cell	CL:0000115	99.07	gold quality
adrenal tissue	UBERON:0018303	99.05	gold quality
mammary duct	UBERON:0001765	99.03	gold quality
epithelium of mammary gland	UBERON:0003244	98.99	gold quality
superior frontal gyrus	UBERON:0002661	98.98	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.95	gold quality
CA1 field of hippocampus	UBERON:0003881	98.92	gold quality
orbitofrontal cortex	UBERON:0004167	98.88	gold quality
cardia of stomach	UBERON:0001162	98.77	gold quality
cranial nerve II	UBERON:0000941	98.76	gold quality
calcaneal tendon	UBERON:0003701	98.71	gold quality
ventricular zone	UBERON:0003053	98.66	gold quality
medial globus pallidus	UBERON:0002477	98.63	gold quality
globus pallidus	UBERON:0001875	98.62	gold quality
corpus callosum	UBERON:0002336	98.62	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	17.38
E-MTAB-5061	yes	14.51
E-CURD-114	yes	7.11
E-CURD-112	yes	6.48
E-HCAD-11	yes	6.35
E-MTAB-10042	yes	5.51
E-MTAB-10485	no	1921.49
E-MTAB-6108	no	686.05
E-MTAB-7606	no	218.95
E-CURD-88	no	216.92
E-HCAD-5	no	16.04
E-GEOD-83139	no	3.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting TTC3, 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-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3941	99.86	70.54	2735

Literature-anchored findings (GeneRIF, showing 8)

• These results suggest that the TTC3-RhoA-CIT-K pathway could be a crucial determinant of in vivo neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program. (PMID:17488780)
• Interaction between TTC3 and Akt may contribute to the clinical symptoms of Down syndrome. (PMID:20059950)
• USP16 and TTC3 were dysregulated in all affected human cells and two mouse models of Down syndrome. (PMID:27586445)
• Overexpressed TTC3 Protein Tends to be Cleaved into Fragments and Form Aggregates in the Nucleus. (PMID:30203323)
• Data suggest that TTC3 may contribute to TGF-beta1-induced EMT and myofibroblast differentiation, potentially through SMURF2 ubiquitylation/proteasomal degradation and subsequent inhibition of SMURF2-mediated suppression of SMAD2 and SMAD3, which in turn induces TTC3 expression. (PMID:30696809)
• Derivation of stem cell line UMi028-A-2 containing a CRISPR/Cas9 induced Alzheimer’s disease risk variant p.S1038C in the TTC3 gene. (PMID:33626494)
• TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment. (PMID:33638766)
• An Alzheimer’s disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons. (PMID:37677864)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc3	ENSDARG00000086075
mus_musculus	Ttc3	ENSMUSG00000040785
rattus_norvegicus	Ttc3	ENSRNOG00000001682

Protein

Protein identifiers

E3 ubiquitin-protein ligase TTC3 — P53804 (reviewed: P53804)

Alternative names: Protein DCRR1, RING finger protein 105, RING-type E3 ubiquitin transferase TTC3, TPR repeat protein D, Tetratricopeptide repeat protein 3

All UniProt accessions (14): P53804, A0A8Q3SJJ4, A0A8Q3WLK8, A0A8Q3WLL9, A0A8Q3WLN3, A0A8Q3WMF6, A8MT23, B4DSZ9, E9PCE7, E9PMP8, E9PMS7, H7BZ57, H7C097, H7C3Z1

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which catalyzes the formation of ‘Lys-48’-polyubiquitin chains. Mediates the ubiquitination and subsequent degradation of phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus. Acts as a terminal regulator of Akt signaling after activation; its phosphorylation by Akt, which is a prerequisite for ubiquitin ligase activity, suggests the existence of a regulation mechanism required to control Akt levels after activation. Positively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation by mediating the ubiquitination and subsequent degradation of SMURF2. Regulates neuronal differentiation by regulating actin remodeling and Golgi organization via a signaling cascade involving RHOA, CIT and ROCK. Inhibits cell proliferation.

Subunit / interactions. Interacts (when phosphorylated on Ser-378) with AKT1, AKT2 and AKT3 (when phosphorylated). Interacts with CIT. Interacts with POLG. Interacts with HSP70. Interacts with SMURF2.

Subcellular location. Nucleus. Cytoplasm. Golgi apparatus.

Tissue specificity. Found in all tissues examined.

Post-translational modifications. Phosphorylation on Ser-378 by Akt is required for ubiquitin ligase activity. Proteolytically cleaved into differently sized N- and C-terminal fragments.

Induction. Up-regulated by TGFB1 signaling.

Pathway. Protein modification; protein ubiquitination.

Isoforms (3)

UniProt ID	Names	Canonical?
P53804-1	TPRDI	yes
P53804-2	TPRDII
P53804-3	TPRDIII

RefSeq proteins (10): NP_001001894, NP_001307632, NP_001307633, NP_001317610, NP_001317611, NP_001317612, NP_001340865, NP_001340866, NP_001340867, NP_003307 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR043866	TTC3/DZIP3_dom	Domain
IPR056870	TTC3/DZIP3/RBM44-like_helical	Domain
IPR056871	WH_TTC3	Domain
IPR056872	TTC3/DZIP3-like_helical	Domain

Pfam: PF13639, PF19179, PF24525, PF24812, PF24905

UniProt features (40 total): sequence conflict 9, region of interest 8, compositionally biased region 6, sequence variant 5, repeat 4, modified residue 3, splice variant 2, chain 1, mutagenesis site 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53804-F1	62.94	0.13

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 (3): 378, 1009, 1061

Mutagenesis-validated functional residues (1):

Position	Phenotype
378	abolishes phosphorylation by akt and impairs ubiquitin ligase activity on akt.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 279 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, ONKEN_UVEAL_MELANOMA_UP, COATES_MACROPHAGE_M1_VS_M2_UP, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, PARK_HSC_AND_MULTIPOTENT_PROGENITORS, MAF_Q6, BASAKI_YBX1_TARGETS_DN, MATTIOLI_MULTIPLE_MYELOMA_SUBGROUPS

GO Biological Process (3): ubiquitin-dependent protein catabolic process (GO:0006511), protein K48-linked ubiquitination (GO:0070936), protein ubiquitination (GO:0016567)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	2
nuclear lumen	2
cytoplasm	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein polyubiquitination	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membraneless organelle	1
endomembrane system	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

59 interactions, top by confidence:

A	B	Type	Score
NPHP1	NPHP4	psi-mi:“MI:0914”(association)	0.930
AKT1	TTC3	psi-mi:“MI:0915”(physical association)	0.640
AKT1	TTC3	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
TTC3	AKT2	psi-mi:“MI:0915”(physical association)	0.580
AKT2	TTC3	psi-mi:“MI:0915”(physical association)	0.580
TTC3	AKT3	psi-mi:“MI:0915”(physical association)	0.520
AKT3	TTC3	psi-mi:“MI:0915”(physical association)	0.520
TTC3	SMURF2	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	TTC3	psi-mi:“MI:0915”(physical association)	0.370
TTC3	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
TTC3	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
Tuba3a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
CEP43	CCHCR1	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	WDR46	psi-mi:“MI:0914”(association)	0.350
Rassf1	TTC31	psi-mi:“MI:0914”(association)	0.350
SMC6	IFT88	psi-mi:“MI:0914”(association)	0.350
WAPL	RPL10	psi-mi:“MI:0914”(association)	0.350
Bach1	SYNM	psi-mi:“MI:0914”(association)	0.350
PARD6A		psi-mi:“MI:0914”(association)	0.350
Cul1	GPS1	psi-mi:“MI:0914”(association)	0.350
Mad2l1bp	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
KRBOX4	ASXL2	psi-mi:“MI:0914”(association)	0.350

BioGRID (150): TTC3 (Two-hybrid), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), TTC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YXX9, A0A7H0DNF0, A6QR20, D3ZSP7, O15050, O61766, O76720, O88196, P0DUE1, P53804, P79161, P79340, Q0V9U8, Q13075, Q18008, Q1LVQ2, Q28579, Q3UPF5, Q5Q0E6, Q5RA75, Q5RBY8, Q5TEA3, Q5U228, Q5XJY6, Q67E01, Q6AX58, Q6NU22, Q6NU51, Q6SJ93, Q6ZN28, Q7KLI1, Q7TPV2, Q86Y13, Q8AXQ3, Q8BGT8, Q8BMD7, Q8N157, Q8QMP8, Q8R3P9, Q8TDB6

Diamond homologs: A2ZLU6, A4K2V0, A5PKG6, A6HD62, D3ZSP7, D7REX8, E4NKF8, E9Q735, F1RBN2, F8RP11, O13754, O13797, O14217, O16259, O35814, O54981, O80742, O81902, O88196, P0C6E7, P0CT30, P15705, P25638, P31948, P53041, P53042, P53804, Q07617, Q0IMG9, Q0JL44, Q14139, Q15785, Q32PZ3, Q388N2, Q3KRD5, Q3ZBR5, Q3ZBZ8, Q43468, Q496Y0, Q4R8N7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
AKT	up-regulates	TTC3	phosphorylation
AKT1	up-regulates	TTC3	phosphorylation
Ub:E2	“up-regulates activity”	TTC3	ubiquitination
TTC3	“down-regulates quantity”	SMURF2	ubiquitination
TTC3	“down-regulates quantity by destabilization”	AKT1	ubiquitination
TTC3	“down-regulates quantity by destabilization”	AKT	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Resolution of Sister Chromatid Cohesion	5	10.3×	2e-03
Mitotic Prometaphase	5	8.2×	4e-03
Separation of Sister Chromatids	5	7.2×	5e-03
Cell Cycle, Mitotic	6	6.9×	3e-03
Diseases of signal transduction by growth factor receptors and second messengers	5	6.8×	6e-03
Cell Cycle	6	5.2×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of blood vessel endothelial cell migration	5	36.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	248
Likely benign	23
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

7025 predictions. Top by Δscore:

Variant	Effect	Δscore
21:37087242:CTTAG:C	acceptor_loss	1.0000
21:37087245:A:AG	acceptor_gain	1.0000
21:37087246:G:GA	acceptor_gain	1.0000
21:37087246:GA:G	acceptor_gain	1.0000
21:37087246:GAC:G	acceptor_gain	1.0000
21:37087246:GACT:G	acceptor_gain	1.0000
21:37087246:GACTT:G	acceptor_gain	1.0000
21:37087397:GGGTG:G	donor_gain	1.0000
21:37087398:GGTGG:G	donor_gain	1.0000
21:37087399:GTG:G	donor_gain	1.0000
21:37087402:G:GG	donor_gain	1.0000
21:37087403:T:A	donor_loss	1.0000
21:37087406:G:GG	donor_gain	1.0000
21:37087832:GGGT:G	acceptor_gain	1.0000
21:37087874:GG:G	donor_gain	1.0000
21:37087875:GG:G	donor_gain	1.0000
21:37088189:A:AG	acceptor_gain	1.0000
21:37088194:A:G	acceptor_gain	1.0000
21:37088245:A:G	acceptor_gain	1.0000
21:37088797:A:G	acceptor_gain	1.0000
21:37088800:A:AG	acceptor_gain	1.0000
21:37088884:GCT:G	donor_gain	1.0000
21:37088887:G:GG	donor_gain	1.0000
21:37091285:T:TA	acceptor_gain	1.0000
21:37091392:T:G	donor_gain	1.0000
21:37091392:T:TG	donor_gain	1.0000
21:37091410:GAAT:G	donor_gain	1.0000
21:37091414:G:GG	donor_gain	1.0000
21:37093991:A:G	acceptor_gain	1.0000
21:37096578:A:AG	acceptor_gain	1.0000

AlphaMissense

7899 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:37144595:T:A	W615R	1.000
21:37144595:T:C	W615R	1.000
21:37148603:T:A	W692R	1.000
21:37148603:T:C	W692R	1.000
21:37148617:A:C	K696N	1.000
21:37148617:A:T	K696N	1.000
21:37150096:T:C	C713R	1.000
21:37096610:G:C	R271P	0.999
21:37140573:G:C	A558P	0.999
21:37140649:G:A	G583E	0.999
21:37144597:G:C	W615C	0.999
21:37144597:G:T	W615C	0.999
21:37147538:T:C	C651R	0.999
21:37147540:T:G	C651W	0.999
21:37148564:T:C	C679R	0.999
21:37148565:G:A	C679Y	0.999
21:37148566:T:G	C679W	0.999
21:37148600:T:C	C691R	0.999
21:37148602:C:G	C691W	0.999
21:37148605:G:C	W692C	0.999
21:37148605:G:T	W692C	0.999
21:37148615:A:G	K696E	0.999
21:37150096:T:A	C713S	0.999
21:37150097:G:A	C713Y	0.999
21:37150097:G:C	C713S	0.999
21:37150098:T:G	C713W	0.999
21:37150111:T:C	C718R	0.999
21:37150112:G:A	C718Y	0.999
21:37150113:T:G	C718W	0.999
21:37156834:T:A	W974R	0.999

dbSNP variants (sampled 300 via entrez): RS1000011480 (21:37178052 T>C), RS1000076582 (21:37132251 T>C), RS1000098498 (21:37170683 T>G), RS1000108163 (21:37185019 A>G), RS1000150330 (21:37102445 A>G), RS1000156416 (21:37091179 G>A), RS1000208393 (21:37123537 G>A,C), RS1000246317 (21:37164347 T>C), RS1000281059 (21:37090619 A>G), RS1000357185 (21:37097127 T>C), RS1000389746 (21:37073965 G>C), RS1000403075 (21:37111906 C>T), RS1000405077 (21:37151618 G>A), RS1000426451 (21:37151782 G>A), RS1000431450 (21:37129639 T>C)

Disease associations

OMIM: gene MIM:602259 | disease phenotypes: MIM:614104

GenCC curated gene-disease

Mondo (1): DYRK1A-related intellectual disability syndrome (MONDO:0013578)

Orphanet (1): DYRK1A-related intellectual disability syndrome (Orphanet:464306)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000685_1	Eye color traits	2.000000e-10
GCST003434_8	Obsessive-compulsive symptoms	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003949	eye color
EFO:0007802	obsessive-compulsive symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	6
trichostatin A	affects cotreatment, increases expression	3
Tretinoin	decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	increases methylation	1
tamibarotene	decreases 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, increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Decitabine	affects expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5QS	UMi028-A-2	Induced pluripotent stem cell	Male
CVCL_B2JX	Abcam HeLa TTC3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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