CRTC3

Summary

CRTC3 (CREB regulated transcription coactivator 3, HGNC:26148) is a protein-coding gene on chromosome 15q26.1, encoding CREB-regulated transcription coactivator 3 (Q6UUV7). Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites.

This gene is a member of the CREB regulated transcription coactivator gene family. This family regulates CREB-dependent gene transcription in a phosphorylation-independent manner and may be selective for cAMP-responsive genes. The protein encoded by this gene may induce mitochondrial biogenesis and attenuate catecholamine signaling in adipose tissue. A translocation event between this gene and Notch coactivator mastermind-like gene 2, which results in a fusion protein, has been reported in mucoepidermoid carcinomas. Alternative splicing results in multiple transcript variants that encode different protein isoforms.

Source: NCBI Gene 64784 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_022769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26148
Approved symbol	CRTC3
Name	CREB regulated transcription coactivator 3
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21868
Ensembl gene	ENSG00000140577
Ensembl biotype	protein_coding
OMIM	608986
Entrez	64784

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 9 protein_coding, 8 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000268184, ENST00000420329, ENST00000558005, ENST00000558167, ENST00000558496, ENST00000558619, ENST00000560047, ENST00000560098, ENST00000560320, ENST00000560927, ENST00000561119, ENST00000561218, ENST00000561255, ENST00000561290, ENST00000686240, ENST00000687075, ENST00000691029, ENST00000692149, ENST00000861172, ENST00000861173, ENST00000861174, ENST00000861175, ENST00000861176

RefSeq mRNA: 2 — MANE Select: NM_022769 NM_001042574, NM_022769

CCDS: CCDS32331, CCDS45348

Canonical transcript exons

ENST00000268184 — 15 exons

Exon	Start	End
ENSE00001228713	90641097	90641199
ENSE00001228723	90638735	90638815
ENSE00001228730	90638446	90638646
ENSE00001228739	90629234	90629532
ENSE00001228811	90641932	90645345
ENSE00002569425	90529923	90530203
ENSE00003514425	90614453	90614488
ENSE00003520185	90607378	90607478
ENSE00003527213	90593636	90593755
ENSE00003535045	90540039	90540137
ENSE00003592472	90604385	90604447
ENSE00003633003	90625776	90625993
ENSE00003644253	90619741	90619790
ENSE00003681456	90602324	90602385
ENSE00003692153	90617883	90617968

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.6432 / max 160.3186, expressed in 1807 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148465	18.1773	1807
148466	1.0822	735
148468	0.1369	36
148463	0.1049	37
148464	0.0774	28
148467	0.0645	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.10	gold quality
saphenous vein	UBERON:0007318	96.84	gold quality
parotid gland	UBERON:0001831	96.42	gold quality
blood vessel layer	UBERON:0004797	96.06	gold quality
visceral pleura	UBERON:0002401	95.27	gold quality
pleura	UBERON:0000977	95.02	gold quality
urethra	UBERON:0000057	94.98	gold quality
inferior olivary complex	UBERON:0002127	94.95	gold quality
parietal pleura	UBERON:0002400	94.91	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.77	gold quality
nipple	UBERON:0002030	94.74	gold quality
popliteal artery	UBERON:0002250	94.31	gold quality
tibial artery	UBERON:0007610	94.30	gold quality
cervix squamous epithelium	UBERON:0006922	94.06	gold quality
inferior vagus X ganglion	UBERON:0005363	93.92	gold quality
cranial nerve II	UBERON:0000941	93.75	gold quality
seminal vesicle	UBERON:0000998	93.67	gold quality
mucosa of stomach	UBERON:0001199	93.67	gold quality
pericardium	UBERON:0002407	93.58	gold quality
mucosa of urinary bladder	UBERON:0001259	93.55	gold quality
right coronary artery	UBERON:0001625	93.21	gold quality
vena cava	UBERON:0004087	93.18	gold quality
adult organism	UBERON:0007023	93.17	gold quality
trachea	UBERON:0003126	92.99	gold quality
germinal epithelium of ovary	UBERON:0001304	92.77	gold quality
synovial joint	UBERON:0002217	92.72	gold quality
aorta	UBERON:0000947	92.65	gold quality
superficial temporal artery	UBERON:0001614	92.64	gold quality
ovary	UBERON:0000992	92.48	gold quality
right ovary	UBERON:0002118	92.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.86
E-MTAB-6075	no	163.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL3, TP53

miRNA regulators (miRDB)

104 targeting CRTC3, 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-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-4481	100.00	66.42	1669
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-5582-3P	99.86	72.48	4221

Literature-anchored findings (GeneRIF, showing 18)

• transducer of regulated cyclic AMP-response element-binding protein 3 (TORC3), a co-activator of CREB, is involved in Tax-induced transcriptional activation from the HTLV-I LTR (PMID:15466468)
• These results strongly suggest that TORCs play a key role in linking these external signals to the transcriptional program of adaptive mitochondrial biogenesis by activating PGC-1alpha gene transcription. (PMID:16980408)
• BCL3 functions as a repressor of HTLV-1 LTR-mediated transcription through interactions with TORC3 (PMID:17644518)
• study reports for the first time a CRTC3-MAML2 fusion gene in a mucoepidermoid carcinoma, as determined by RT-PCR and sequencing. (PMID:18050304)
• Mucoepidermoid carcinomas possessing CRTC3-MAML2 fusion may be associated with favorable clinicopathological features and patients may be younger than those with CRTC1-MAML2 fusion or those with no detectable gene fusion. (PMID:19749740)
• As a common human CRTC3 variant with increased transcriptional activity is associated with adiposity in two distinct Mexican-American cohorts, results suggest that adipocyte CRTC3 may play a role in the development of obesity in humans (PMID:21164481)
• CRTC3 plays a selective role in mitochondrial biogenesis in response to rotenone (PMID:21536665)
• mucoepidermoid carcinoma of the salivary glands positive for CRTC1-MAML2 or CRTC3-MAML2 fusion formed a favourable tumour subset that was distinct from fusion-negative cases (PMID:21668476)
• Metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands did not harbor CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, or MAML2 gene rearrangement. (PMID:24121173)
• The CRTC3 polymorphism rs3862434 is associated with the plasma level of total cholesterol, and rs11635252 is associated with the risks of overweight and hypertriglyceridemia in a Chinese Han population. (PMID:24264430)
• revealing neither correlation between the cellular composition and CRTC1-MAML2 fusions nor presence of CRTC3-MAML2 fusions in cutaneous hidradenoma (PMID:27402217)
• findings suggest further characterization of MECs is needed before considering the CRTC1/3-MAML2 gene fusion as a prognostic biomarker (PMID:28438292)
• CRTC3-MAML2 gene fusion occurs in hidradenomas. (PMID:29079171)
• CRTC3 polymorphism was associated with the onset of acute coronary syndrome in Han Chinese patients, which may be related to the imbalance of the lipid metabolism (PMID:29979427)
• Pancreatic mucoepidermoid carcinoma does not have CRTC1/3-MAML2 fusion gene and MAML2 gene rearrangement. (PMID:30138216)
• Colorectal cancer risk variants rs10161980 and rs7495132 are associated with cancer survival outcome by a recessive mode of inheritance. (PMID:33411955)
• TORC2/3-mediated DUSP1 upregulation is essential for human decidualization. (PMID:33780908)
• Morphological and biological properties of silica nanoparticles for CRTC3-siRNA delivery and downregulation of the RGS2 expression in preadipocytes. (PMID:33947275)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	crtc3	ENSDARG00000052114
mus_musculus	Crtc3	ENSMUSG00000030527
rattus_norvegicus	Crtc3	ENSRNOG00000011975
drosophila_melanogaster	Crtc	FBGN0036746
caenorhabditis_elegans	crtc-1	WBGENE00021237

Paralogs (2): CRTC1 (ENSG00000105662), CRTC2 (ENSG00000160741)

Protein

Protein identifiers

CREB-regulated transcription coactivator 3 — Q6UUV7 (reviewed: Q6UUV7)

Alternative names: Transducer of regulated cAMP response element-binding protein 3

All UniProt accessions (5): A0A8I5KTH9, A0A8I5QJV4, Q6UUV7, H0YK33, H0YK64

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 ‘Ser-133’ phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR).

Subunit / interactions. Binding, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1 enhances recruitment of TAF4 to the promoter. ‘Arg-314’ in the bZIP domain of CREB1 is essential for this interaction. Interacts (when phosphorylated at Ser-162 and Se-273) with 14-3-3 proteins. Interacts with YWHAE. Interacts (when phosphorylated at Ser-391) with phosphatase PP2A catalytic subunit PPP2CA and regulatory subunits PPP2R1A and PPP2R2A. Interacts, via the N-terminal with the ankyrin repeats of BCL3, to form a complex with CREB1 on CRE and TxRE responsive elements and represses HTLV-1 LTR-mediated transcription. (Microbial infection) Interacts with HTLV-1 protein Tax; this interaction enhances tax transcriptional activity.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Predominantly expressed in B and T lymphocytes. Highest levels in lung. Also expressed in brain, colon, heart, kidney, ovary, and prostate. Weak expression in liver, pancreas, muscle, small intestine, spleen and stomach.

Post-translational modifications. Phosphorylation/dephosphorylation states of Ser-273 are required for regulating transduction of CREB activity. CRTCs/TORCs are inactive when phosphorylated, and active when dephosphorylated at this site. May be phosphorylated at Ser-391 by MAPK3/ERK1 and/or MAPK1/ERK2 or by some cyclin-dependent kinases such as CDK1,CDK2 or CDK5. Following adenylyl cyclase activation, dephosphorylated at Ser-162 and Ser-273 resulting in its dissociation from 14-3-3 proteins probably promoting CRTC3 translocation into the nucleus.

Similarity. Belongs to the TORC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UUV7-1	1	yes
Q6UUV7-3	3

RefSeq proteins (2): NP_001036039, NP_073606* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024783	TORC_N	Domain
IPR024784	TORC_M	Domain
IPR024785	TORC_C	Domain
IPR024786	TORC	Family

Pfam: PF12884, PF12885, PF12886

UniProt features (27 total): modified residue 12, region of interest 5, sequence variant 2, sequence conflict 2, compositionally biased region 2, chain 1, cross-link 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UUV7-F1	49.61	0.07

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 (13): 160, 162, 273, 329, 332, 370, 391, 396, 410, 443, 232, 4, 62

Mutagenesis-validated functional residues (1):

Position	Phenotype
282	translocates to the cytoplasm. represses basal torc3 activity towards creb.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-9707616	Heme signaling
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2

MSigDB gene sets: 195 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PROTEIN_HOMOTETRAMERIZATION, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, MARTINEZ_RB1_TARGETS_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, GOBP_RESPONSE_TO_CAMP, GOBP_ADRENERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_CAMP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP

GO Biological Process (9): lipid catabolic process (GO:0016042), macrophage activation (GO:0042116), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of lipid catabolic process (GO:0050995), protein homotetramerization (GO:0051289), cellular response to cAMP (GO:0071320), negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway (GO:0071878), energy homeostasis (GO:0097009), obsolete positive regulation of CREB transcription factor activity (GO:0032793)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), cAMP response element binding protein binding (GO:0008140), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial biogenesis	1
Cellular responses to stress	1
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
positive regulation of DNA-templated transcription	2
lipid metabolic process	1
catabolic process	1
myeloid leukocyte activation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of catabolic process	1
lipid catabolic process	1
negative regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
protein homooligomerization	1
protein tetramerization	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
adenylate cyclase-activating adrenergic receptor signaling pathway	1
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
multicellular organismal-level homeostasis	1
transcription coregulator activity	1
DNA-binding transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRTC3	SIK2	Q9H0K1	805
CRTC3	CREB1	P16220	803
CRTC3	SIK1	P57059	671
CRTC3	A0A0B4J2F2	A0A0B4J2F2	662
CRTC3	PPARGC1A	Q9UBK2	636
CRTC3	RGS2	P41220	608
CRTC3	SIK3	Q9Y2K2	588
CRTC3	PRKACA	P17612	552
CRTC3	PRKACB	P22694	552
CRTC3	PRKACG	P22612	551
CRTC3	CRTC2	Q53ET0	524
CRTC3	CALR	P27797	513
CRTC3	CRTC1	Q6UUV9	507
CRTC3	TCL1B	O95988	492
CRTC3	FOXO1	Q12778	459

IntAct

75 interactions, top by confidence:

A	B	Type	Score
POLD1	POLD2	psi-mi:“MI:0914”(association)	0.910
CRTC3	YWHAH	psi-mi:“MI:0914”(association)	0.710
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CRTC3	CA13	psi-mi:“MI:0915”(physical association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
rep	SBNO1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
MAGEA10	POTEF	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
DCAF7	CLASP2	psi-mi:“MI:0914”(association)	0.510
CRTC3	KLHL12	psi-mi:“MI:0915”(physical association)	0.490
KLHL12	CRTC3	psi-mi:“MI:0915”(physical association)	0.490
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YAP1	CRTC3	psi-mi:“MI:0407”(direct interaction)	0.440
	CRTC3	psi-mi:“MI:0407”(direct interaction)	0.410
	CRTC3	psi-mi:“MI:0915”(physical association)	0.400
CRTC3	PCNA	psi-mi:“MI:0915”(physical association)	0.370
HCCS	MROH1	psi-mi:“MI:0914”(association)	0.350
CPAP	CCP110	psi-mi:“MI:0914”(association)	0.350
Sec24c	SEC31A	psi-mi:“MI:0914”(association)	0.350
GTSE1	HIP1	psi-mi:“MI:0914”(association)	0.350
CLTC		psi-mi:“MI:0914”(association)	0.350
Chmp4b	BDP1	psi-mi:“MI:0914”(association)	0.350
LRP8	TYK2	psi-mi:“MI:0914”(association)	0.350
PCDHB15	HLA-A	psi-mi:“MI:0914”(association)	0.350

BioGRID (89): CRTC3 (Affinity Capture-MS), CRTC3 (Proximity Label-MS), CRTC3 (Proximity Label-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS), CRTC3 (Affinity Capture-MS)

ESM2 similar proteins: A8E4V2, B5DF41, E1BEQ5, O15079, O88479, P01101, P12841, P70365, Q02225, Q0VA20, Q13625, Q1LY51, Q3UHI0, Q3UIL6, Q4PJW2, Q4VCS5, Q56TN0, Q56TT7, Q5RDH2, Q5XG16, Q5ZKN5, Q5ZLN7, Q62415, Q68FF7, Q6AYT4, Q6IQ23, Q6NZE7, Q6UUV7, Q7SXC6, Q7Z309, Q80U23, Q8BHS8, Q8BM65, Q8CG79, Q8IY63, Q8ND83, Q8VHG2, Q91X84, Q96E09, Q99LJ0

Diamond homologs: Q08E26, Q0IHT3, Q157S1, Q3LRZ1, Q3U182, Q52KS4, Q53ET0, Q68ED7, Q6UUV7, Q6UUV9, Q91X84, Q95XA8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SIK1	down-regulates	CRTC3	phosphorylation
CRTC3	up-regulates	BCL3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
Activation of BAD and translocation to mitochondria	7	102.5×	3e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	90.4×	5e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	90.4×	5e-11
Activation of BH3-only proteins	8	76.4×	1e-11
Intrinsic Pathway for Apoptosis	8	45.0×	4e-10
RHO GTPases activate PKNs	7	42.7×	1e-08
FOXO-mediated transcription	5	32.3×	1e-05
Apoptosis	8	25.8×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	37.9×	6e-06
intracellular protein localization	8	14.4×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2501 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90530200:GCGG:G	donor_gain	1.0000
15:90530202:GG:G	donor_gain	1.0000
15:90530202:GGGT:G	donor_loss	1.0000
15:90530203:GG:G	donor_gain	1.0000
15:90530203:GGTGA:G	donor_loss	1.0000
15:90530204:G:C	donor_loss	1.0000
15:90530204:G:GG	donor_gain	1.0000
15:90530205:T:G	donor_loss	1.0000
15:90540148:A:G	donor_gain	1.0000
15:90593779:G:GT	donor_gain	1.0000
15:90604373:T:TA	acceptor_gain	1.0000
15:90617881:A:AG	acceptor_gain	1.0000
15:90617882:G:GG	acceptor_gain	1.0000
15:90619791:G:GG	donor_gain	1.0000
15:90625774:A:AG	acceptor_gain	1.0000
15:90625775:G:GG	acceptor_gain	1.0000
15:90625775:GT:G	acceptor_gain	1.0000
15:90638444:AGAT:A	acceptor_gain	1.0000
15:90638445:GATG:G	acceptor_gain	1.0000
15:90638643:CCAGG:C	donor_loss	1.0000
15:90638645:AGG:A	donor_loss	1.0000
15:90638647:G:A	donor_loss	1.0000
15:90638648:T:A	donor_loss	1.0000
15:90641092:TCCAG:T	acceptor_loss	1.0000
15:90641196:CCAGG:C	donor_loss	1.0000
15:90641197:CAGG:C	donor_loss	1.0000
15:90641200:G:GA	donor_loss	1.0000
15:90641201:T:A	donor_loss	1.0000
15:90641916:T:A	acceptor_gain	1.0000
15:90641917:G:A	acceptor_gain	1.0000

AlphaMissense

4003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90530114:T:C	F15L	1.000
15:90530115:T:C	F15S	1.000
15:90530115:T:G	F15C	1.000
15:90530116:C:A	F15L	1.000
15:90530116:C:G	F15L	1.000
15:90530121:A:T	E17V	1.000
15:90530127:T:A	I19N	1.000
15:90530127:T:C	I19T	1.000
15:90530127:T:G	I19S	1.000
15:90530133:T:C	L21P	1.000
15:90530150:G:C	A27P	1.000
15:90530168:T:C	F33L	1.000
15:90530169:T:C	F33S	1.000
15:90530169:T:G	F33C	1.000
15:90530170:C:A	F33L	1.000
15:90530170:C:G	F33L	1.000
15:90530178:T:C	L36P	1.000
15:90530117:A:C	S16R	0.999
15:90530119:T:A	S16R	0.999
15:90530119:T:G	S16R	0.999
15:90530120:G:A	E17K	0.999
15:90530122:G:C	E17D	0.999
15:90530122:G:T	E17D	0.999
15:90530125:G:C	K18N	0.999
15:90530125:G:T	K18N	0.999
15:90530129:G:C	A20P	0.999
15:90530142:A:C	Q24P	0.999
15:90530146:A:C	R25S	0.999
15:90530146:A:T	R25S	0.999
15:90530148:A:C	Q26P	0.999

dbSNP variants (sampled 300 via entrez): RS1000027365 (15:90600560 T>C), RS1000038445 (15:90535551 G>A,C), RS1000042469 (15:90573441 C>G), RS1000076197 (15:90595426 G>A), RS1000127387 (15:90534794 G>A), RS1000129376 (15:90539128 C>T), RS1000189506 (15:90642482 C>T), RS1000193411 (15:90567635 C>T), RS1000273475 (15:90609292 T>C), RS1000281343 (15:90570594 G>A,T), RS1000337130 (15:90621505 A>G), RS1000368075 (15:90621845 A>G), RS1000371445 (15:90567920 T>C), RS1000390263 (15:90544761 C>G), RS1000392581 (15:90538839 G>A)

Disease associations

OMIM: gene MIM:608986 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000905_13	Information processing speed	3.000000e-06
GCST001725_50	Inflammatory bowel disease	9.000000e-11
GCST002929_18	Chromium levels	6.000000e-06
GCST003207_2	Response to exercise (triglyceride level interaction)	7.000000e-06
GCST003518_37	Daytime sleep phenotypes	9.000000e-06
GCST003631_4	Gastroesophageal reflux disease	2.000000e-07
GCST004131_105	Inflammatory bowel disease	3.000000e-07
GCST004133_39	Ulcerative colitis	3.000000e-06
GCST005149_20	Colorectal cancer	2.000000e-06
GCST005150_28	Colorectal cancer	1.000000e-07
GCST006288_168	Heel bone mineral density	5.000000e-07
GCST006288_336	Heel bone mineral density	7.000000e-08
GCST006288_442	Heel bone mineral density	1.000000e-14
GCST006661_175	Male-pattern baldness	2.000000e-11
GCST008363_1	Offspring birth weight	5.000000e-09
GCST009839_1	Chronic postoperative pain	2.000000e-06
GCST010243_71	Apolipoprotein B levels	4.000000e-08
GCST90002381_633	Eosinophil count	8.000000e-16
GCST90002382_426	Eosinophil percentage of white cells	1.000000e-14

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004363	information processing speed
EFO:0007681	triglyceride change measurement
EFO:0007768	response to exercise
EFO:0007828	daytime rest measurement
EFO:0009270	heel bone mineral density
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010640	chronic post-operative pain measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	2
Hydrogen Peroxide	affects cotreatment, increases expression, decreases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Chelating Agents	affects binding, decreases expression	1
Copper	affects binding, decreases expression	1
Methapyrilene	decreases methylation	1
Nickel	increases 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_LB42	PathHunter U2OS TORC3 Nuclear Translocation	Cancer cell line	Female

Clinical trials (associated diseases)

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