TRIM23

Summary

TRIM23 (tripartite motif containing 23, HGNC:660) is a protein-coding gene on chromosome 5q12.3, encoding E3 ubiquitin-protein ligase TRIM23 (P36406). Acts as an E3 ubiquitin-protein ligase.

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein is also a member of the ADP ribosylation factor family of guanine nucleotide-binding family of proteins. Its carboxy terminus contains an ADP-ribosylation factor domain and a guanine nucleotide binding site, while the amino terminus contains a GTPase activating protein domain which acts on the guanine nucleotide binding site. The protein localizes to lysosomes and the Golgi apparatus. It plays a role in the formation of intracellular transport vesicles, their movement from one compartment to another, and phopholipase D activation. Three alternatively spliced transcript variants for this gene have been described.

Source: NCBI Gene 373 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_001656

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:660
Approved symbol	TRIM23
Name	tripartite motif containing 23
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	ARD1, RNF46
Ensembl gene	ENSG00000113595
Ensembl biotype	protein_coding
OMIM	601747
Entrez	373

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000231524, ENST00000274327, ENST00000381018, ENST00000505205, ENST00000506400, ENST00000508808, ENST00000513794

RefSeq mRNA: 3 — MANE Select: NM_001656 NM_001656, NM_033227, NM_033228

CCDS: CCDS3986, CCDS3987, CCDS43322

Canonical transcript exons

ENST00000231524 — 11 exons

Exon	Start	End
ENSE00000748872	65594521	65594645
ENSE00000748876	65596421	65596531
ENSE00000748924	65597051	65597180
ENSE00000748929	65604911	65605045
ENSE00000749080	65610861	65611043
ENSE00000749118	65611603	65611881
ENSE00000749236	65618093	65618255
ENSE00001407304	65589690	65591948
ENSE00001896330	65624194	65624333
ENSE00003592391	65609243	65609458
ENSE00003637881	65614098	65614219

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 93.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7112 / max 430.6084, expressed in 1770 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61952	14.7112	1770

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	93.47	gold quality
frontal pole	UBERON:0002795	92.85	gold quality
calcaneal tendon	UBERON:0003701	91.74	gold quality
cortical plate	UBERON:0005343	91.12	gold quality
corpus callosum	UBERON:0002336	90.83	gold quality
prefrontal cortex	UBERON:0000451	90.73	gold quality
Brodmann (1909) area 10	UBERON:0013541	89.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.88	gold quality
inferior vagus X ganglion	UBERON:0005363	88.88	gold quality
adrenal tissue	UBERON:0018303	88.79	gold quality
substantia nigra pars compacta	UBERON:0001965	88.75	gold quality
ventricular zone	UBERON:0003053	88.60	gold quality
paraflocculus	UBERON:0005351	88.48	gold quality
pons	UBERON:0000988	88.32	gold quality
occipital lobe	UBERON:0002021	88.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.55	gold quality
primary visual cortex	UBERON:0002436	87.38	gold quality
frontal cortex	UBERON:0001870	87.31	gold quality
middle frontal gyrus	UBERON:0002702	87.20	gold quality
neocortex	UBERON:0001950	87.14	gold quality
subthalamic nucleus	UBERON:0001906	87.07	gold quality
ventral tegmental area	UBERON:0002691	86.62	gold quality
lateral globus pallidus	UBERON:0002476	86.19	gold quality
ganglionic eminence	UBERON:0004023	86.18	gold quality
cerebral cortex	UBERON:0000956	86.11	gold quality
cingulate cortex	UBERON:0003027	86.05	gold quality
anterior cingulate cortex	UBERON:0009835	86.00	gold quality
tendon	UBERON:0000043	85.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

183 targeting TRIM23, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-340-5P	100.00	72.50	4437
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-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955

Literature-anchored findings (GeneRIF, showing 13)

• Data are consistent with a potential function for ADP-ribosylation factor domain protein 1 as an E3 ubiquitin ligase in cells. (PMID:15684077)
• The authors present a novel role for TRIM23 that is specific to UL144-mediated activation of NF-kappaB during the course of virus infection. (PMID:19176615)
• conclude that TRIM23-mediated ubiquitin conjugation to NEMO is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses (PMID:20724660)
• TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARgamma2. (PMID:25905670)
• Our results indicate that TRIM23 enzymatic activity requires RING dimerization, consistent with the general model of TRIM activation (PMID:28681414)
• work identifies the TRIM23-TBK1-p62 axis as a key component of selective autophagy and further reveals a role for K27-linked ubiquitination in GTPase-dependent TBK1 activation (PMID:28871090)
• TRIM23 may be associated with progression of gastric cancer (PMID:30477642)
• study identifies TRIM27 as a novel positive regulator of HCV replication (PMID:30847745)
• Data report that the Us11 protein targets TRIM23, which is a key regulator of autophagy-mediated antiviral defense mediated by TBK1. In virus-infected cells, the Us11 protein drastically reduces the formation of autophagosomes mediated by TRIM23 or TBK1. This autophagy-inhibitory effect is attributable to the binding of the Us11 protein to the ARF domain in TRIM23. (PMID:31189704)
• Study found that TRIM23 was upregulated in lung adenocarcinoma (LUAD), and elevated TRIM23 expression was correlated with high expression of NF-kappaB, poor cellular differentiation, and adverse overall survival and disease-free survival. Furthermore, TRIM23 acted as an oncogene in LUAD and promoted cisplatin-resistance by regulating glucose metabolism. (PMID:31677335)
• TRIM23 overexpression is a poor prognostic factor and contributes to carcinogenesis in colorectal cancer. (PMID:32227572)
• Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels. (PMID:33957127)
• Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23. (PMID:34903664)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim23	ENSDARG00000069420
mus_musculus	Trim23	ENSMUSG00000021712
rattus_norvegicus	Trim23	ENSRNOG00000012354
caenorhabditis_elegans		WBGENE00000180

Paralogs (30): ARF5 (ENSG00000004059), SAR1A (ENSG00000079332), ARFRP1 (ENSG00000101246), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARL8B (ENSG00000134108), ARF3 (ENSG00000134287), ARL3 (ENSG00000138175), ARL5C (ENSG00000141748), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), SAR1B (ENSG00000152700), ARL5A (ENSG00000162980), ARF6 (ENSG00000165527), ARL5B (ENSG00000165997), ARF4 (ENSG00000168374), ARL13B (ENSG00000169379), ARL13A (ENSG00000174225), ARL10 (ENSG00000175414), ARL4D (ENSG00000175906), ARL14 (ENSG00000179674), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL9 (ENSG00000196503), ARL2 (ENSG00000213465), ARL16 (ENSG00000214087), ARL17B (ENSG00000228696)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRIM23 — P36406 (reviewed: P36406)

Alternative names: ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, RING finger protein 46, RING-type E3 ubiquitin transferase TRIM23, Tripartite motif-containing protein 23

All UniProt accessions (4): P36406, D6R9E9, D6RBN4, D6RD22

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an E3 ubiquitin-protein ligase. Plays an essential role in autophagy activation during viral infection. Mechanistically, activates TANK-binding kinase 1/TBK1 by facilitating its dimerization and ability to phosphorylate the selective autophagy receptor SQSTM1. In order to achieve this function, TRIM23 mediates ‘Lys-27’-linked auto-ubiquitination of its ADP-ribosylation factor (ARF) domain to induce its GTPase activity and its recruitment to autophagosomes. (Microbial infection) Mediates TRAF6 auto-ubiquitination in the presence of human cytomegalovirus protein UL144, resulting in the virally controlled activation of NF-kappa-B stimulation at early times of HCMV infection.

Subunit / interactions. Homodimer. Interacts with PSCD1. Interacts with UBE2D2. Interacts with TBK1 (via N-terminal kinase domain) and p62/SQSTM1. (Microbial infection) Interacts with human cytomegalovirus protein UL144; this interaction might cause autoubiquitination of TRAF6, leading to NF-kappa-B activation.

Subcellular location. Cytoplasm. Endomembrane system. Golgi apparatus membrane. Lysosome membrane.

Domain organisation. The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity. This domain is catalytically active as a dimer.

Pathway. Protein modification; protein ubiquitination.

Similarity. In the C-terminal section; belongs to the small GTPase superfamily. Arf family.

Isoforms (3)

UniProt ID	Names	Canonical?
P36406-1	Alpha	yes
P36406-2	Beta
P36406-3	Gamma

RefSeq proteins (3): NP_001647, NP_150230, NP_150231 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR003649	Bbox_C	Domain
IPR005225	Small_GTP-bd	Domain
IPR006689	Small_GTPase_ARF/SAR	Family
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR017907	Znf_RING_CS	Conserved_site
IPR024156	Small_GTPase_ARF	Family
IPR027370	Znf-RING_euk	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00025, PF00643, PF13445

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (25 total): strand 5, mutagenesis site 4, helix 3, binding site 3, zinc finger region 2, turn 2, splice variant 2, chain 1, sequence variant 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5VZV	X-RAY DIFFRACTION	1.81
5VZW	X-RAY DIFFRACTION	2.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36406-F1	82.49	0.32

Functional residue map

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

Ligand- & substrate-binding residues (3): 411–418; 454–458; 513–516

Mutagenesis-validated functional residues (4):

Position	Phenotype
34	loss of e3 ubiquitin-protein ligase activity.
53	loss of e3 ubiquitin-protein ligase activity.
418	maintains gtpase activity. increases interaction with pscd1.
458	suppresses gtpase activity. decreases interaction with pscd1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 204 (showing top): AHRARNT_01, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GCANCTGNY_MYOD_Q6, AAGCCAT_MIR135A_MIR135B, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_66, MODULE_331, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, DOANE_RESPONSE_TO_ANDROGEN_DN

GO Biological Process (6): intracellular protein transport (GO:0006886), positive regulation of autophagy (GO:0010508), vesicle-mediated transport (GO:0016192), protein ubiquitination (GO:0016567), innate immune response (GO:0045087), immune system process (GO:0002376)

GO Molecular Function (12): GTPase activity (GO:0003924), ubiquitin-protein transferase activity (GO:0004842), GTP binding (GO:0005525), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), GDP binding (GO:0019003), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (9): Golgi membrane (GO:0000139), nucleus (GO:0005634), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), lysosome (GO:0005764), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
guanyl ribonucleotide binding	2
catalytic activity	2
intracellular membrane-bounded organelle	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
transport	1
cellular process	1
protein modification by small protein conjugation	1
immune response	1
defense response to symbiont	1
biological_process	1
ribonucleoside triphosphate phosphatase activity	1
ubiquitin-like protein transferase activity	1
purine ribonucleoside triphosphate binding	1
enzyme regulator activity	1
molecular function activator activity	1
transition metal ion binding	1
anion binding	1
protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
lytic vacuole	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

3387 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM23	CYTH2	Q99418	797
TRIM23	CYTH1	Q15438	765
TRIM23	AP1AR	Q63HQ0	764
TRIM23	TRAF3	Q13114	739
TRIM23	CYTH4	Q9UIA0	686
TRIM23	TRIM56	Q9BRZ2	684
TRIM23	CYTH3	O43739	640
TRIM23	TRIM25	Q14258	622
TRIM23	TRAT1	Q6PIZ9	622
TRIM23	TRIM44	Q96DX7	582
TRIM23	TRIM8	Q9BZR9	544
TRIM23	TRIM54	Q9BYV2	542
TRIM23	TRIM41	Q8WV44	534
TRIM23	TRIM27	P14373	533
TRIM23	TRIM21	P19474	529
TRIM23	TRIM5	Q9C035	529

IntAct

753 interactions, top by confidence:

A	B	Type	Score
TBC1D22B	TRIM23	psi-mi:“MI:0915”(physical association)	0.830
TRIM23	ZNF581	psi-mi:“MI:0915”(physical association)	0.830
TRIM23	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.830
ZNF581	TRIM23	psi-mi:“MI:0915”(physical association)	0.830
TRIM23	TRIM23	psi-mi:“MI:0915”(physical association)	0.820
SNAI1	TRIM23	psi-mi:“MI:0915”(physical association)	0.780
GPANK1	TRIM23	psi-mi:“MI:0915”(physical association)	0.780
TRIM23	ATPAF2	psi-mi:“MI:0915”(physical association)	0.780
TRIM23	IQUB	psi-mi:“MI:0915”(physical association)	0.780
TRIM23	SNAI1	psi-mi:“MI:0915”(physical association)	0.780
TRIM23	GPANK1	psi-mi:“MI:0915”(physical association)	0.780
IQUB	TRIM23	psi-mi:“MI:0915”(physical association)	0.780
TRIM23	COX5B	psi-mi:“MI:0915”(physical association)	0.740
ARHGEF3	TRIM23	psi-mi:“MI:0915”(physical association)	0.740
TRIM23	ARHGEF3	psi-mi:“MI:0915”(physical association)	0.740
TRIM23	KRT6A	psi-mi:“MI:0915”(physical association)	0.720
TRIM23	HOXB5	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP3	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
TRIM23	AQP1	psi-mi:“MI:0915”(physical association)	0.720
TRIM23	SORBS3	psi-mi:“MI:0915”(physical association)	0.720
CDR2	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
TRIM23	FAM90A1	psi-mi:“MI:0915”(physical association)	0.720
FAM133A	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
MORN4	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
TRIM23	ZNF564	psi-mi:“MI:0915”(physical association)	0.720
FAM110A	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
RAMAC	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
TRIM23	SMG9	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (470): TRIM23 (Two-hybrid), TRIM23 (Two-hybrid), TRIM23 (Two-hybrid), BAG1 (Two-hybrid), CDR2 (Two-hybrid), COX5B (Two-hybrid), DCX (Two-hybrid), DOCK2 (Two-hybrid), GATA2 (Two-hybrid), HOXB5 (Two-hybrid), KIFC3 (Two-hybrid), KRT6A (Two-hybrid), LGALS8 (Two-hybrid), LMO2 (Two-hybrid), PHF1 (Two-hybrid)

ESM2 similar proteins: A1E2V0, A5D8Q0, A9JTP3, A9ULZ2, B1B1A0, O08863, O62640, P33279, P36406, P36407, P42573, P51784, P98170, Q13049, Q13075, Q13489, Q13490, Q1L8G6, Q24307, Q4R8E0, Q5BKL8, Q60989, Q62210, Q63185, Q6P5D3, Q6ZPS6, Q6ZUJ8, Q7Z2W4, Q80Z32, Q8C7M3, Q8CH72, Q8JHV9, Q8K337, Q8N1W1, Q8R151, Q90660, Q95M71, Q95M72, Q96P09, Q9BQI3

Diamond homologs: A6NH57, B5FYQ0, O00909, O23778, O48649, O48920, P0CM16, P0CM17, P0DH91, P11076, P18085, P19146, P22274, P25160, P26990, P26991, P34212, P34727, P36397, P36405, P36406, P36407, P36579, P37996, P38116, P40616, P40940, P40945, P40946, P40994, P49076, P49702, P51643, P51644, P51645, P51646, P51821, P51822, P51823, P51824

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TRIM23	“up-regulates activity”	TBK1	binding
TRIM23	“up-regulates activity”	TRAF6	ubiquitination
Ub:E2	“up-regulates activity”	TRIM23	ubiquitination
TRIM23	“up-regulates quantity by stabilization”	PPARG	ubiquitination
IKBKB	“down-regulates activity”	TRIM23	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2163 predictions. Top by Δscore:

Variant	Effect	Δscore
5:65594643:CAG:C	acceptor_gain	1.0000
5:65594646:C:CC	acceptor_gain	1.0000
5:65594651:C:CT	acceptor_gain	1.0000
5:65594651:C:T	acceptor_gain	1.0000
5:65597048:TACC:T	donor_loss	1.0000
5:65597049:A:AC	donor_gain	1.0000
5:65597049:AC:A	donor_gain	1.0000
5:65597050:C:CA	donor_gain	1.0000
5:65597050:CC:C	donor_gain	1.0000
5:65597050:CCA:C	donor_gain	1.0000
5:65597050:CCAA:C	donor_gain	1.0000
5:65597050:CCAAT:C	donor_gain	1.0000
5:65597176:TTATC:T	acceptor_gain	1.0000
5:65597180:CCTAC:C	acceptor_loss	1.0000
5:65604906:ATTAC:A	donor_loss	1.0000
5:65604907:TTAC:T	donor_loss	1.0000
5:65604908:TAC:T	donor_loss	1.0000
5:65604909:ACCTT:A	donor_loss	1.0000
5:65604910:C:CG	donor_loss	1.0000
5:65605041:TCATC:T	acceptor_gain	1.0000
5:65605042:CATC:C	acceptor_gain	1.0000
5:65605042:CATCC:C	acceptor_gain	1.0000
5:65605044:TC:T	acceptor_gain	1.0000
5:65605044:TCC:T	acceptor_loss	1.0000
5:65605045:CC:C	acceptor_gain	1.0000
5:65605046:C:CC	acceptor_gain	1.0000
5:65609238:CCTA:C	donor_loss	1.0000
5:65609239:CTAC:C	donor_loss	1.0000
5:65609240:TAC:T	donor_loss	1.0000
5:65609242:CCTG:C	donor_gain	1.0000

AlphaMissense

3745 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:65596446:C:A	W465C	1.000
5:65596446:C:G	W465C	1.000
5:65596448:A:G	W465R	1.000
5:65596448:A:T	W465R	1.000
5:65596480:T:C	D454G	1.000
5:65596480:T:G	D454A	1.000
5:65596482:C:A	W453C	1.000
5:65596482:C:G	W453C	1.000
5:65596484:A:G	W453R	1.000
5:65596484:A:T	W453R	1.000
5:65596527:A:C	F438L	1.000
5:65596527:A:T	F438L	1.000
5:65596528:A:G	F438S	1.000
5:65596529:A:G	F438L	1.000
5:65597110:T:A	K417I	1.000
5:65597128:C:T	G411E	1.000
5:65597129:C:G	G411R	1.000
5:65597129:C:T	G411R	1.000
5:65611635:A:G	C205R	1.000
5:65611642:G:C	C202W	1.000
5:65611644:A:G	C202R	1.000
5:65611678:G:C	C190W	1.000
5:65611680:A:G	C190R	1.000
5:65611716:A:G	C178R	1.000
5:65611759:G:C	H163Q	1.000
5:65611759:G:T	H163Q	1.000
5:65611761:G:C	H163D	1.000
5:65611783:A:C	H155Q	1.000
5:65611783:A:T	H155Q	1.000
5:65611800:A:G	C150R	1.000

dbSNP variants (sampled 300 via entrez): RS1000080053 (5:65594929 C>G,T), RS1000117029 (5:65593378 T>G), RS1000123254 (5:65593071 T>C), RS1000170190 (5:65599857 T>C), RS1000328476 (5:65621104 G>A,C,T), RS1000404994 (5:65606384 T>C), RS1000588590 (5:65614745 A>G), RS1000692680 (5:65621176 TC>T), RS1000723264 (5:65620985 G>A), RS1000820569 (5:65611939 T>C), RS1000933987 (5:65619723 T>C), RS1001144166 (5:65620459 A>C), RS1001181475 (5:65593030 T>C), RS1001220898 (5:65593793 A>G), RS1001337131 (5:65625804 C>T)

Disease associations

OMIM: gene MIM:601747 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010701_121	Cortical surface area (MOSTest)	6.000000e-11
GCST010702_62	Subcortical volume (MOSTest)	6.000000e-12
GCST010703_77	Brain morphology (MOSTest)	2.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	affects methylation, increases expression	2
Doxorubicin	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
1-nitropyrene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
seocalcitol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Decitabine	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Gold	decreases expression	1
Ketoconazole	affects expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TT91	HAP1 TRIM23 (-) 1	Cancer cell line	Male
CVCL_TT92	HAP1 TRIM23 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder