TRIM26

Summary

TRIM26 (tripartite motif containing 26, HGNC:12962) is a protein-coding gene on chromosome 6p22.1, encoding Tripartite motif-containing protein 26 (Q12899). E3 ubiquitin-protein ligase which regulates the IFN-beta production and antiviral response downstream of various DNA-encoded pattern-recognition receptors (PRRs).

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. The protein localizes to cytoplasmic bodies. Although the function of the protein is unknown, the RING domain suggests that the protein may have DNA-binding activity. The gene localizes to the major histocompatibility complex (MHC) class I region on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 7726 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_003449

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12962
Approved symbol	TRIM26
Name	tripartite motif containing 26
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	RNF95
Ensembl gene	ENSG00000234127
Ensembl biotype	protein_coding
OMIM	600830
Entrez	7726

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 41 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000416596, ENST00000418026, ENST00000434785, ENST00000437089, ENST00000453195, ENST00000454678, ENST00000480999, ENST00000487829, ENST00000861717, ENST00000861718, ENST00000861719, ENST00000861720, ENST00000861721, ENST00000861722, ENST00000861723, ENST00000861724, ENST00000861725, ENST00000861726, ENST00000861727, ENST00000861728, ENST00000861729, ENST00000861730, ENST00000861731, ENST00000861732, ENST00000861733, ENST00000861734, ENST00000861735, ENST00000861736, ENST00000861737, ENST00000861738, ENST00000861739, ENST00000861740, ENST00000861741, ENST00000919560, ENST00000919561, ENST00000919562, ENST00000963434, ENST00000963435, ENST00000963436, ENST00000963437, ENST00000963438, ENST00000963439, ENST00000963440

RefSeq mRNA: 2 — MANE Select: NM_003449 NM_001242783, NM_003449

CCDS: CCDS4678

Canonical transcript exons

ENST00000327357 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7597 / max 296.9287, expressed in 1787 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72512	10.9467	1764
72511	7.2452	1734
72510	1.5679	690

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	92.35	gold quality
leukocyte	CL:0000738	91.56	gold quality
duodenum	UBERON:0002114	91.50	gold quality
monocyte	CL:0000576	91.47	gold quality
liver	UBERON:0002107	90.87	gold quality
lymph node	UBERON:0000029	90.49	gold quality
esophagus mucosa	UBERON:0002469	90.29	gold quality
vermiform appendix	UBERON:0001154	90.19	gold quality
right lobe of liver	UBERON:0001114	90.06	gold quality
tonsil	UBERON:0002372	90.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.46	gold quality
blood	UBERON:0000178	89.36	gold quality
bone marrow	UBERON:0002371	89.27	gold quality
adult mammalian kidney	UBERON:0000082	89.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.99	gold quality
esophagus	UBERON:0001043	88.77	gold quality
gall bladder	UBERON:0002110	88.74	gold quality
mucosa of transverse colon	UBERON:0004991	88.58	gold quality
sural nerve	UBERON:0015488	88.51	gold quality
small intestine	UBERON:0002108	88.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.18	gold quality
fallopian tube	UBERON:0003889	88.18	gold quality
saliva-secreting gland	UBERON:0001044	88.14	gold quality
islet of Langerhans	UBERON:0000006	88.10	gold quality
urinary bladder	UBERON:0001255	88.03	gold quality
mucosa of stomach	UBERON:0001199	87.99	gold quality
bone marrow cell	CL:0002092	87.94	gold quality
placenta	UBERON:0001987	87.87	gold quality
minor salivary gland	UBERON:0001830	87.79	gold quality
endometrium	UBERON:0001295	87.63	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-106540	no	233.48
E-CURD-10	no	49.64
E-ANND-3	no	1.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JUN	Activation

miRNA regulators (miRDB)

78 targeting TRIM26, 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-4692	100.00	67.32	2066
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-1827	99.63	68.57	3265

Literature-anchored findings (GeneRIF, showing 18)

• The study reports no associations between polymorphisms in TRIM26 and the risk of aspirin-exacerbated respiratory disease in both logistic and regression analyses. (PMID:22294275)
• In addition to confirming one of the top findings in the meta-analysis, TRIM26, RNF5 and HLA-DRB3 have been identified as potential candidate genes for schizophrenia. (PMID:22433715)
• Down-regulation of TRIM26 is associated with worse prognosis of hepatocellular carcinoma. (PMID:26043685)
• Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response (PMID:26611359)
• This paper demonstrates the importance of TRIM26 in regulating the cellular levels of NTH1, particularly under conditions of oxidative stress. (PMID:29610152)
• We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC. (PMID:29956500)
• TRIM26 overexpression inhibited cell proliferation, migration, and invasion in Papillary thyroid carcinoma cells. TRIM26 overexpression also suppressed the epithelial-to-mesenchymal transition process. (PMID:30927273)
• Overexpression of tripartite motif containing 26 inhibits non-small cell lung cancer cell growth by suppressing PI3K/AKT signaling. (PMID:32052576)
• Inhibition of tripartite motif containing 26 inhibits non-small cell lung cancer cell growth. (PMID:33305515)
• TRIM26 Facilitates HSV-2 Infection by Downregulating Antiviral Responses through the IRF3 Pathway. (PMID:33419081)
• Knockdown of TRIM26 inhibits the proliferation, migration and invasion of bladder cancer cells through the Akt/GSK3beta/beta-catenin pathway. (PMID:33549581)
• Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma. (PMID:34732716)
• Comprehensive analysis of expression profiles and prognosis of TRIM genes in human kidney clear cell carcinoma. (PMID:35617983)
• Tripartite Motif Containing 26 is a Positive Predictor for Endometrial Carcinoma Patients and Regulates Cell Survival in Endometrial Carcinoma. (PMID:36108622)
• TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling. (PMID:37591850)
• The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma. (PMID:37872147)
• TRIM26 restricts Epstein-Barr virus infection in nasopharyngeal epithelial cells through K48-linked ubiquitination of HSP-90beta. (PMID:38038978)
• TRIM26 inhibits clear cell renal cell carcinoma progression through destabilizing ETK and thus inactivation of AKT/mTOR signaling. (PMID:38773612)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim26	ENSMUSG00000024457
rattus_norvegicus	Trim26	ENSRNOG00000032930

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890)

Protein

Protein identifiers

Tripartite motif-containing protein 26 — Q12899 (reviewed: Q12899)

Alternative names: Acid finger protein, RING finger protein 95, Zinc finger protein 173

All UniProt accessions (5): Q12899, A0A024RCP3, A2AE48, A2AE50, Q5SPU2

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which regulates the IFN-beta production and antiviral response downstream of various DNA-encoded pattern-recognition receptors (PRRs). Also plays a central role in determining the response to different forms of oxidative stress by controlling levels of DNA glycosylases NEIL1, NEIL3 and NTH1 that are involved in repair of damaged DNA. Promotes nuclear IRF3 ubiquitination and proteasomal degradation. Bridges together TBK1 and NEMO during the innate response to viral infection leading to the activation of TBK1. Positively regulates LPS-mediated inflammatory innate immune response by catalyzing the ‘Lys-11’-linked polyubiquitination of TAB1 to enhance its activation and subsequent NF-kappa-B and MAPK signaling. In a manner independent of its catalytic activity, inhibits WWP2, a SOX2-directed E3 ubiquitin ligase, and thus protects SOX2 from polyubiquitination and proteasomal degradation. Ubiquitinates the histone acetyltransferase protein complex component PHF20 and thereby triggers its degradation in the nucleus after its recruitment by the histone demethylase KDM6B, serving as a scaffold protein. Upon induction by TGF-beta, ubiquitinates the TFIID component TAF7 for proteasomal degradation. Induces ferroptosis by ubiquitinating SLC7A11, a critical protein for lipid reactive oxygen species (ROS) scavenging. Inhibits directly hepatitis B virus replication by mediating HBX ubiquitination and subsequent degradation. (Microbial infection) Promotes herpes simplex virus type 2/HHV-2 infection in vaginal epithelial cells by decreasing the nuclear localization of IRF3, the primary mediator of type I interferon activation.

Subunit / interactions. Interacts with TBK1; this interaction bridges together TBK1 and NEMO in order to activate TBK1. Interacts with INCA1.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Autoubiquitinates upon viral infection. In turn, autoubiquitinated TRIM26 recruits NEMO and bridges TBK1-NEMO interaction.

Induction. By cytokine TGF-beta and binding of activated SMAD3 to the TRIM26 promoter. Upon herpes simplex virus type 2/HHV-2 infection. By type I interferon.

Similarity. Belongs to the TRIM/RBCC family.

RefSeq proteins (2): NP_001229712, NP_003440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13765, PF15227

UniProt features (13 total): binding site 4, zinc finger region 2, chain 1, domain 1, sequence variant 1, mutagenesis site 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12899-F1	83.49	0.55

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 (4): 130; 102; 105; 124

Mutagenesis-validated functional residues (1):

Position	Phenotype
16	strong loss of ubiquitination activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 176 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_PROTEIN_K11_LINKED_UBIQUITINATION, GOBP_POSITIVE_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, BLALOCK_ALZHEIMERS_DISEASE_UP, DER_IFN_BETA_RESPONSE_UP, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_DEFENSE_RESPONSE_TO_VIRUS

GO Biological Process (10): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), suppression of viral release by host (GO:0044790), innate immune response (GO:0045087), host-mediated suppression of symbiont invasion (GO:0046597), protein K11-linked ubiquitination (GO:0070979), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), immune system process (GO:0002376), canonical NF-kappaB signal transduction (GO:0007249), non-canonical NF-kappaB signal transduction (GO:0038061), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (5): 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 (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	2
cellular anatomical structure	2
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
defense response to virus	1
immune response	1
defense response to symbiont	1
innate immune response	1
host-mediated perturbation of symbiont process	1
protein polyubiquitination	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
biological_process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	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 membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM26	TRAT1	Q6PIZ9	772
TRIM26	TBK1	Q9UHD2	737
TRIM26	PPP1R11	O60927	692
TRIM26	IRF3	Q14653	633
TRIM26	PHF20	Q9BVI0	602
TRIM26	NT5C2	P49902	565
TRIM26	ITIH3	Q06033	493
TRIM26	METTL1	Q9UBP6	490
TRIM26	TRIM14	Q14142	490
TRIM26	VRK2	Q86Y07	490
TRIM26	PIN1	Q13526	487
TRIM26	TRIM17	Q9Y577	487
TRIM26	HLA-A	P01891	485
TRIM26	KDM6B	O15054	483
TRIM26	TAB1	Q15750	482

IntAct

144 interactions, top by confidence:

A	B	Type	Score
TRIM26	THAP1	psi-mi:“MI:0915”(physical association)	0.720
DDRGK1	UFL1	psi-mi:“MI:0914”(association)	0.710
MAGEA6	TRIM26	psi-mi:“MI:0915”(physical association)	0.670
TRIM26	MAGEA6	psi-mi:“MI:0915”(physical association)	0.670
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
RPS7	RPL5	psi-mi:“MI:0914”(association)	0.640
TLE5	TRIM26	psi-mi:“MI:0915”(physical association)	0.560
TRIM26	TLE5	psi-mi:“MI:0915”(physical association)	0.560
TRIM26	BIVM	psi-mi:“MI:0915”(physical association)	0.560
TRIM26	EPN3	psi-mi:“MI:0915”(physical association)	0.560
EPN2	TRIM26	psi-mi:“MI:0915”(physical association)	0.560
TRIM26	BEND7	psi-mi:“MI:0915”(physical association)	0.560
EPN3	TRIM26	psi-mi:“MI:0915”(physical association)	0.560
MACROH2A1	TRIM26	psi-mi:“MI:0915”(physical association)	0.560
TRIM26	RNF10	psi-mi:“MI:0915”(physical association)	0.550
ZNF169	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF707	ZNF316	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
ZNF223	PPM1G	psi-mi:“MI:0914”(association)	0.530

BioGRID (273): TRIM26 (Two-hybrid), THAP1 (Two-hybrid), TRIM26 (Affinity Capture-MS), TRIM26 (Reconstituted Complex), TRIM26 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), TRIM26 (Affinity Capture-MS), TRIM26 (Proximity Label-MS), TRIM26 (Proximity Label-MS), TRIM26 (Proximity Label-MS)

ESM2 similar proteins: A6NK02, A6NLU0, D4ABM4, F8VTS6, O00635, O19085, O77666, P14373, P15533, P62603, P86448, P86449, Q12899, Q2T9Z0, Q3UWZ0, Q495X7, Q58DK8, Q5BK82, Q5D7H7, Q5D7I6, Q5E9G4, Q5RBG2, Q5SZ99, Q5TM55, Q62158, Q62191, Q640S6, Q6AZZ1, Q6PGR9, Q7TPM3, Q7YR32, Q7YR33, Q7YR34, Q7YRV4, Q80X56, Q86WT6, Q8BVP1, Q8K243, Q8N7C3, Q8N9V2

Diamond homologs: A0JN74, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NK02, A6NLI5, B1H278, C9J1S8, K7N6K2, O00635, O15553, O19085, O77666, P0CI25, P0CI26, P14373, P15533, P18892, P19474, Q02084, Q0PF16, Q12899, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2T9Z0, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3UWZ0, Q3ZEE5, Q495X7, Q587N6, Q587N7, Q58DK8

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM26	ubiquitination
TRIM26	“down-regulates quantity by destabilization”	IRF3	polyubiquitination
TRIM26	“down-regulates quantity by destabilization”	IRF3	ubiquitination
TRIM26	“down-regulates quantity”	NEIL1	ubiquitination
TRIM26	“down-regulates quantity by destabilization”	NTHL1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	7	9.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1335 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30186554:GCTCA:G	acceptor_gain	1.0000
6:30186555:CTCA:C	acceptor_gain	1.0000
6:30186555:CTCAC:C	acceptor_gain	1.0000
6:30186556:TCA:T	acceptor_gain	1.0000
6:30186556:TCAC:T	acceptor_loss	1.0000
6:30186556:TCACT:T	acceptor_gain	1.0000
6:30186557:CA:C	acceptor_gain	1.0000
6:30186557:CAC:C	acceptor_gain	1.0000
6:30186558:AC:A	acceptor_loss	1.0000
6:30186559:C:CC	acceptor_gain	1.0000
6:30186559:CTGT:C	acceptor_loss	1.0000
6:30186560:T:A	acceptor_loss	1.0000
6:30186568:C:CT	acceptor_gain	1.0000
6:30186569:A:T	acceptor_gain	1.0000
6:30186844:T:TA	donor_gain	1.0000
6:30189200:C:CC	acceptor_gain	1.0000
6:30189416:AC:A	donor_gain	1.0000
6:30189417:CC:C	donor_gain	1.0000
6:30189427:C:A	donor_gain	1.0000
6:30189432:AGG:A	donor_gain	1.0000
6:30189459:T:C	donor_gain	1.0000
6:30189531:TAC:T	acceptor_gain	1.0000
6:30189531:TACC:T	acceptor_loss	1.0000
6:30189532:ACCT:A	acceptor_loss	1.0000
6:30189533:CCTA:C	acceptor_loss	1.0000
6:30189534:CTA:C	acceptor_loss	1.0000
6:30189535:T:G	acceptor_loss	1.0000
6:30196511:CTCA:C	donor_loss	1.0000
6:30196513:CA:C	donor_loss	1.0000
6:30196514:A:AG	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000036075 (6:30192149 G>A), RS1000275815 (6:30208045 G>A), RS1000407444 (6:30212013 G>C), RS1000429375 (6:30201363 A>T), RS1000608957 (6:30209910 CA>C), RS1000685797 (6:30203511 G>A,T), RS1000747081 (6:30210191 C>A,T), RS1001006752 (6:30184673 G>A), RS1001060561 (6:30185045 T>G), RS1001127814 (6:30213413 G>T), RS1001166510 (6:30186573 G>A), RS1001358972 (6:30206049 T>G), RS1001410386 (6:30213579 G>A), RS1001569922 (6:30214882 G>A), RS1001579895 (6:30214410 G>A)

Disease associations

OMIM: gene MIM:600830 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST001242_13	Schizophrenia	2.000000e-12
GCST001631_1	Schizophrenia	1.000000e-16
GCST002324_6	Anger	8.000000e-07
GCST004521_121	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_132	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_2	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_210	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_263	Autism spectrum disorder or schizophrenia	7.000000e-17
GCST004521_268	Autism spectrum disorder or schizophrenia	7.000000e-12
GCST004521_269	Autism spectrum disorder or schizophrenia	7.000000e-11
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_44	Autism spectrum disorder or schizophrenia	2.000000e-17
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST004748_100	Lung cancer	5.000000e-18
GCST004749_84	Lung cancer in ever smokers	2.000000e-12
GCST004750_50	Squamous cell lung carcinoma	8.000000e-13
GCST005232_23	Neuroticism	8.000000e-09
GCST005541_11	Sarcoidosis (Lofgren’s syndrome vs non-Lofgren’s syndrome)	8.000000e-20
GCST006269_701	General cognitive ability	1.000000e-09
GCST007201_366	Schizophrenia	1.000000e-21
GCST007934_5	Medication use (anti-inflammatory and antirheumatic products, non-steroids)	7.000000e-10
GCST007993_27	Asthma (adult onset)	7.000000e-07
GCST007995_23	Asthma (childhood onset)	3.000000e-08
GCST010244_256	Triglyceride levels	2.000000e-21
GCST010245_148	LDL cholesterol levels	2.000000e-19
GCST012228_97	Waist-hip index	2.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0003015	aggressive behavior
EFO:0007660	neuroticism measurement
EFO:0004337	intelligence
EFO:0009935	Non-steroidal anti-inflammatory and antirheumatic product use measurement
EFO:1002011	adult onset asthma
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004348	hematocrit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects cotreatment, increases expression, decreases expression	3
bisphenol A	affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation	2
Ethyl Methanesulfonate	decreases expression, increases expression	2
Methyl Methanesulfonate	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression, affects cotreatment	1
AKT activator SC79	decreases reaction, affects phosphorylation, affects expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
PCI 5002	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Adenine	decreases expression	1
Arsenic	affects methylation	1
Colchicine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Diethylstilbestrol	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases 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_TT98	HAP1 TRIM26 (-) 1	Cancer cell line	Male
CVCL_TT99	HAP1 TRIM26 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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