NLRC3

Summary

NLRC3 (NLR family CARD domain containing 3, HGNC:29889) is a protein-coding gene on chromosome 16p13.3, encoding NLR family CARD domain-containing protein 3 (Q7RTR2). Negative regulator of the innate immune response.

This gene encodes a NOD-like receptor family member. The encoded protein is a cytosolic regulator of innate immunity. This protein directly interacts with stimulator of interferon genes (STING), to prevent its proper trafficking, resulting in disruption of STING-dependent activation of the innate immune response. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 197358 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 238 total — 1 pathogenic
• MANE Select transcript: NM_178844

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29889
Approved symbol	NLRC3
Name	NLR family CARD domain containing 3
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CLR16.2, FLJ00348, NOD3
Ensembl gene	ENSG00000167984
Ensembl biotype	protein_coding
OMIM	615648
Entrez	197358

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000324659, ENST00000359128, ENST00000603055, ENST00000615877, ENST00000618137, ENST00000872255

RefSeq mRNA: 1 — MANE Select: NM_178844 NM_178844

CCDS: CCDS73817

Canonical transcript exons

ENST00000359128 — 20 exons

Exon	Start	End
ENSE00001227619	3552196	3552279
ENSE00003472863	3549697	3549780
ENSE00003474806	3544246	3544329
ENSE00003485949	3564859	3565060
ENSE00003505524	3556911	3556994
ENSE00003517150	3565319	3565380
ENSE00003537254	3567243	3567324
ENSE00003541774	3542191	3542274
ENSE00003545773	3549142	3549225
ENSE00003558156	3561702	3561788
ENSE00003568771	3554242	3554325
ENSE00003582686	3577149	3577403
ENSE00003590462	3563009	3564758
ENSE00003604810	3548670	3548753
ENSE00003614329	3550414	3550497
ENSE00003623702	3543425	3543508
ENSE00003662281	3557593	3557676
ENSE00003666788	3542692	3542775
ENSE00003741955	3539033	3541915
ENSE00003789793	3548135	3548218

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 91.75.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7557 / max 119.1715, expressed in 268 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156036	2.3168	246
156035	0.2947	106
156034	0.1442	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	91.75	gold quality
granulocyte	CL:0000094	91.53	gold quality
ileal mucosa	UBERON:0000331	87.10	gold quality
blood	UBERON:0000178	84.18	gold quality
lymph node	UBERON:0000029	84.07	gold quality
endothelial cell	CL:0000115	83.85	gold quality
spleen	UBERON:0002106	80.00	gold quality
vermiform appendix	UBERON:0001154	79.48	gold quality
epithelium of nasopharynx	UBERON:0001951	77.53	gold quality
tonsil	UBERON:0002372	75.41	gold quality
amniotic fluid	UBERON:0000173	74.50	gold quality
epithelial cell of pancreas	CL:0000083	73.62	silver quality
superficial temporal artery	UBERON:0001614	73.56	gold quality
caecum	UBERON:0001153	72.60	gold quality
jejunal mucosa	UBERON:0000399	72.58	gold quality
bone marrow cell	CL:0002092	72.43	silver quality
oviduct epithelium	UBERON:0004804	71.99	gold quality
palpebral conjunctiva	UBERON:0001812	70.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.69	gold quality
bone marrow	UBERON:0002371	70.02	gold quality
small intestine	UBERON:0002108	69.75	gold quality
gall bladder	UBERON:0002110	69.08	gold quality
right uterine tube	UBERON:0001302	68.37	gold quality
colonic epithelium	UBERON:0000397	66.87	gold quality
duodenum	UBERON:0002114	65.86	gold quality
parietal pleura	UBERON:0002400	65.78	gold quality
cortical plate	UBERON:0005343	65.58	gold quality
visceral pleura	UBERON:0002401	65.55	gold quality
upper lobe of left lung	UBERON:0008952	65.18	gold quality
apex of heart	UBERON:0002098	64.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.39
E-MTAB-6379	no	654.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting NLRC3, 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-4533	100.00	69.48	2758
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6892-3P	99.68	66.40	1178

Literature-anchored findings (GeneRIF, showing 15)

• This report describes the first cloning and characterization of a novel CATERPILLER gene, CLR16.2 that is located on human chromosome 16. The protein encoded by this gene has a typical NBD-LRR configuration. (PMID:15705585)
• Post-transcriptional inhibition of luciferase reporter assays by the Nod-like receptor proteins NLRX1 and NLRC3. (PMID:22718770)
• NLRC3 inhibited Toll-like receptor (TLR)-dependent activation of the transcription factor NF-kappaB by interacting with the TLR signaling adaptor TRAF6 (PMID:22863753)
• overexpression of NLRC3 with NLRP3/cryopyrin inflammasome components suppresses pro-caspase-1 cleavage and IL-1beta processing. (PMID:25277106)
• The extent of NLRC3 and AIM2 gene reduction was correlated with cancer progression. (PMID:26378020)
• NLRX1, NLRP12 and NLRC3 negatively modulate the host immune response following virus exposure. (Review) (PMID:26763980)
• The NLRC3 interferes with the assembly and activity of the NALP3 inflammasome complex by competing with ASC for pro-caspase-1 binding. (PMID:28584053)
• NLRC3 promoted K48-linked polyubiquitination and degradation of interleukin-1 receptor-associated kinase 1 (IRAK1). (PMID:28731142)
• Down-regulated expression of NLRC3 may play an important role in cancer progression and prognosis of HCC by acting as a tumor suppressor. (PMID:30081150)
• expression of NLRC3 was significantly associated with CD8+ T cells infiltration (PMID:31303617)
• NLRC3 silencing accelerates the invasion of hepatocellular carcinoma cell via IL-6/JAK2/STAT3 pathway activation. (PMID:32584509)
• [Knockdown of NLRC3 promotes proliferation and invasion of human colon cancer cells]. (PMID:34533122)
• NLRC3 is a potential prognostic biomarker that is correlated with immune cell infiltration in lung adenocarcinoma. (PMID:36808166)
• NLRC3 deficiency promotes hypoxia-induced pulmonary hypertension development via IKK/NF-kappaB p65/HIF-1alpha pathway. (PMID:37586455)
• Decoding the IBD paradox: A triadic interplay between REG3, enterococci, and NOD2. (PMID:37708849)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nlrc3	ENSDARG00000103146
mus_musculus	Nlrc3	ENSMUSG00000049871
rattus_norvegicus	Nlrc3	ENSRNOG00000024210

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

NLR family CARD domain-containing protein 3 — Q7RTR2 (reviewed: Q7RTR2)

Alternative names: CARD15-like protein, Caterpiller protein 16.2, NACHT, LRR and CARD domains-containing protein 3, Nucleotide-binding oligomerization domain protein 3

All UniProt accessions (4): A0A087WZ24, C3VPR7, Q7RTR2, H3BLT9

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of the innate immune response. Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating ‘Lys-63’-linked ubiquitination and leaving unchanged the degradative ‘Lys-48’-linked ubiquitination. Inhibits the PI3K-AKT-mTOR pathway possibly by directly interacting with the posphatidylinositol 3-kinase regulatory subunit p85 (PIK3R1/PIK3R2) and disrupting the association between PIK3R1/PIK3R2 and the catalytic subunit p110 (PIK3CA/PIK3CB/PIK3CD) and reducing PIK3R1/PIK3R2 activation. Via its regulation of the PI3K-AKT-mTOR pathway, controls cell proliferation, predominantly in intestinal epithelial cells. May also affect NOD1- or NOD2-mediated NF-kappa-B activation. Might also affect the inflammatory response by preventing NLRP3 inflammasome formation, CASP1 cleavage and IL1B maturation.

Subunit / interactions. Directly interacts (via CARD) with TMEM173/STING; this interaction reduces TMEM173 trafficking to the perinuclear region in response to interferon stimulatory DNA. Also interacts, but to a lesser extent, with TBK1. Interacts with TRAF6; this interaction results in decreased TRAF6 ‘Lys-63’-linked polyubiquitination, but leaves ‘Lys-48’-linked chains unchanged, promoting TRAF6 protein degradation. Interacts with PIK3R1/PIK3R2; this interaction disrupts the association between PIK3R1/PIK3R2 and the p110 catalytic subunit PIK3CA/PIK3CB/PIK3CD and reduces PIK3R1/PIK3R2 activation. Weakly interacts with PYCARD/ASC. Interacts with CASP1 and CASP5.

Subcellular location. Cytoplasm.

Domain organisation. The leucine-rich repeat domain may reduce the interaction with TMEM173/STING.

Induction. In primary T-cells, down-regulated upon T-cell receptor activation. Down-regulated in peritoneal macrophages soon after the beginning of LPS stimulation. Levels start increasing again after 3 days of LPS treatment.

Similarity. Belongs to the NLRP family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q7RTR2-1	1	yes
Q7RTR2-2	2
Q7RTR2-3	3
Q7RTR2-4	4

RefSeq proteins (1): NP_849172* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR007111	NACHT_NTPase	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041075	NOD1/2_WH	Domain
IPR041267	NLRP_HD2	Domain
IPR051261	NLR	Family

Pfam: PF05729, PF13516, PF17776, PF17779

UniProt features (30 total): repeat 16, splice variant 4, mutagenesis site 2, chain 1, domain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, binding site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTR2-F1	86.91	0.66

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 (1): 145–152

Mutagenesis-validated functional residues (2):

Position	Phenotype
457–460	strong decrease of traf6-binding.
582–585	almost no effect on traf6-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3270619	IRF3-mediated induction of type I IFN

MSigDB gene sets: 183 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_6_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (19): canonical NF-kappaB signal transduction (GO:0007249), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), negative regulation of interferon-alpha production (GO:0032687), negative regulation of interferon-beta production (GO:0032688), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), T cell activation (GO:0042110), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), negative regulation of innate immune response (GO:0045824), negative regulation of fibroblast proliferation (GO:0048147), negative regulation of epithelial cell proliferation (GO:0050680), negative regulation of inflammatory response (GO:0050728), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), negative regulation of cytokine production involved in inflammatory response (GO:1900016), negative regulation of NLRP3 inflammasome complex assembly (GO:1900226), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), negative regulation of immune system process (GO:0002683), regulation of innate immune response (GO:0045088), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (4): ATP binding (GO:0005524), phosphatidylinositol 3-kinase regulatory subunit binding (GO:0036312), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), centriolar satellite (GO:0034451), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
STING mediated induction of host immune responses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of intracellular signal transduction	3
negative regulation of type I interferon production	2
negative regulation of cytokine production	2
negative regulation of defense response	2
negative regulation of response to external stimulus	2
innate immune response	2
negative regulation of cell population proliferation	2
cytoplasm	2
intracellular signaling cassette	1
interferon-alpha production	1
regulation of interferon-alpha production	1
interferon-beta production	1
regulation of interferon-beta production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
lymphocyte activation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of response to biotic stimulus	1
regulation of innate immune response	1
negative regulation of immune response	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
inflammatory response	1
regulation of inflammatory response	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
negative regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
negative regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
non-canonical NF-kappaB signal transduction	1

Protein interactions and networks

STRING

1195 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRC3	TRAF6	Q9Y4K3	732
NLRC3	CASP1	P29466	682
NLRC3	NLRC4	Q9NPP4	660
NLRC3	NAIP	Q13075	617
NLRC3	TRAF3	Q13114	606
NLRC3	MEFV	O15553	571
NLRC3	NLRC5	Q86WI3	544
NLRC3	RNF26	Q9BY78	539
NLRC3	IKBKB	O14920	505
NLRC3	ZDHHC1	Q8WTX9	499
NLRC3	AIM2	O14862	494
NLRC3	AMFR	P26442	462
NLRC3	IL18	Q14116	460
NLRC3	RIGI	O95786	439
NLRC3	MAVS	Q7Z434	439

IntAct

7 interactions, top by confidence:

A	B	Type	Score
NLRC3	PYCARD	psi-mi:“MI:0915”(physical association)	0.560
NLRC3	PYCARD	psi-mi:“MI:0403”(colocalization)	0.560
NLRC3	ACTC1	psi-mi:“MI:0915”(physical association)	0.400
NLRC3	Traf6	psi-mi:“MI:0915”(physical association)	0.400
ELF3	NLRC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): NLRC3 (Affinity Capture-MS), NLRC3 (Proximity Label-MS), NLRC3 (Affinity Capture-MS), NLRC3 (Affinity Capture-MS), HSP90B1 (Cross-Linking-MS (XL-MS)), HSP90AB1 (Cross-Linking-MS (XL-MS)), HSP90AA1 (Cross-Linking-MS (XL-MS)), NLRC3 (Cross-Linking-MS (XL-MS)), STX12 (Cross-Linking-MS (XL-MS)), NLRC3 (Affinity Capture-Western)

ESM2 similar proteins: A2ASA8, A5PJJ5, A6NE52, A6NHZ5, B6CZ46, E9QAM5, G7PWZ3, P08571, P10810, P33076, P52824, P79621, P86243, Q15048, Q15345, Q1L8H0, Q28680, Q32PG9, Q3U1Y4, Q3UJB3, Q3UWY1, Q3V1N1, Q3V3V9, Q3ZBI5, Q569B5, Q5BK65, Q5DU56, Q5M936, Q63035, Q63691, Q640Z9, Q66H52, Q68EF8, Q6F5E8, Q6GPH6, Q6P5E8, Q6QNU9, Q6R5P0, Q7RTR2, Q80VA5

Diamond homologs: Q5DU56, Q7RTR2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	159
Likely benign	20
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1455963	NC_000016.9:g.(?3293141)(3929917_?)del	Pathogenic

SpliceAI

3098 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3542189:A:AC	donor_gain	1.0000
16:3542190:C:CC	donor_gain	1.0000
16:3542275:C:CC	acceptor_gain	1.0000
16:3542279:G:C	acceptor_gain	1.0000
16:3542279:G:GC	acceptor_gain	1.0000
16:3542690:A:AC	donor_gain	1.0000
16:3542691:C:CC	donor_gain	1.0000
16:3543420:CTT:C	donor_loss	1.0000
16:3543421:TTA:T	donor_loss	1.0000
16:3543422:TAC:T	donor_loss	1.0000
16:3543423:A:AC	donor_gain	1.0000
16:3543423:A:C	donor_loss	1.0000
16:3543423:ACT:A	donor_gain	1.0000
16:3543424:C:CA	donor_gain	1.0000
16:3543424:CT:C	donor_gain	1.0000
16:3543424:CTC:C	donor_gain	1.0000
16:3543424:CTCGA:C	donor_gain	1.0000
16:3543507:GA:G	acceptor_gain	1.0000
16:3543509:C:CC	acceptor_gain	1.0000
16:3544244:A:AC	donor_gain	1.0000
16:3544245:C:CC	donor_gain	1.0000
16:3548133:A:AC	donor_gain	1.0000
16:3548134:C:CC	donor_gain	1.0000
16:3548134:CT:C	donor_gain	1.0000
16:3548668:A:AC	donor_gain	1.0000
16:3548669:C:CC	donor_gain	1.0000
16:3549140:A:AC	donor_gain	1.0000
16:3549140:ACT:A	donor_gain	1.0000
16:3549141:C:CC	donor_gain	1.0000
16:3549141:CT:C	donor_gain	1.0000

AlphaMissense

6909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3544317:G:C	N928K	0.991
16:3544317:G:T	N928K	0.991
16:3548206:G:C	N900K	0.991
16:3548206:G:T	N900K	0.991
16:3564092:C:G	R282P	0.991
16:3564147:A:G	W264R	0.991
16:3564147:A:T	W264R	0.991
16:3564184:G:C	N251K	0.991
16:3564184:G:T	N251K	0.991
16:3557664:G:C	N676K	0.989
16:3557664:G:T	N676K	0.989
16:3556982:G:C	N704K	0.988
16:3556982:G:T	N704K	0.988
16:3563735:C:T	G401D	0.987
16:3563554:A:C	F461L	0.986
16:3563554:A:T	F461L	0.986
16:3563556:A:G	F461L	0.986
16:3563726:G:T	A404D	0.986
16:3549213:G:C	N844K	0.985
16:3549213:G:T	N844K	0.985
16:3563546:G:T	A464D	0.984
16:3563389:G:C	F516L	0.983
16:3563389:G:T	F516L	0.983
16:3563391:A:G	F516L	0.983
16:3563549:G:T	A463E	0.983
16:3563578:G:C	F453L	0.983
16:3563578:G:T	F453L	0.983
16:3563580:A:G	F453L	0.983
16:3563692:A:C	F415L	0.983
16:3563692:A:T	F415L	0.983

dbSNP variants (sampled 300 via entrez): RS1000015304 (16:3543863 T>C), RS1000024548 (16:3542852 G>A), RS1000078264 (16:3555028 G>T), RS1000088153 (16:3577154 G>A,C), RS1000127911 (16:3557857 G>A), RS1000183230 (16:3573765 C>G), RS1000222887 (16:3558112 C>T), RS1000235721 (16:3574088 T>C), RS1000251215 (16:3567822 C>T), RS1000286178 (16:3548781 A>G), RS1000441585 (16:3578278 C>A,T), RS1000486251 (16:3547606 G>T), RS1000520807 (16:3574852 C>T), RS1000743661 (16:3552709 A>G,T), RS1000855976 (16:3548866 G>A)

Disease associations

OMIM: gene MIM:615648 | disease phenotypes: MIM:180849

GenCC curated gene-disease

Mondo (1): Rubinstein-Taybi syndrome (MONDO:0019188)

Orphanet (1): Rubinstein-Taybi syndrome (Orphanet:783)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002783_169	Body mass index	7.000000e-10
GCST002783_223	Body mass index	2.000000e-10
GCST002783_569	Body mass index	8.000000e-08
GCST004519_8	Body mass index (adult)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012415	Rubinstein-Taybi Syndrome	C05.116.099.370.797; C05.660.207.850; C10.597.606.360.700; C16.131.077.804; C16.131.260.790; C16.131.621.207.850; C16.320.180.790

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — NOD-like receptor family

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
licochalcone B	decreases expression	1
Arsenic	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01619644	PHASE2	COMPLETED	Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
NCT04122742	Not specified	UNKNOWN	Diagnosis of RSTS: Identification of the Acetylation Profiles as Epigenetic Markers for Assessing Causality of CREBBP and EP300 Variants.
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.
NCT06740162	Not specified	RECRUITING	Physical Activity and Community EmPOWERment Project