NUMBL

Summary

NUMBL (NUMB like endocytic adaptor protein, HGNC:8061) is a protein-coding gene on chromosome 19q13.2, encoding Numb-like protein (Q9Y6R0). Plays a role in the process of neurogenesis.

Involved in cytokine-mediated signaling pathway. Predicted to be active in cytoplasm and glutamatergic synapse.

Source: NCBI Gene 9253 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_004756

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8061
Approved symbol	NUMBL
Name	NUMB like endocytic adaptor protein
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	NUMB-R, CTG3a, CAG3A, TNRC23, NUMBR, NUMBLIKE
Ensembl gene	ENSG00000105245
Ensembl biotype	protein_coding
OMIM	604018
Entrez	9253

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000252891, ENST00000540131, ENST00000593367, ENST00000595741, ENST00000598759, ENST00000598773, ENST00000598779, ENST00000599594, ENST00000599786, ENST00000600636, ENST00000600967, ENST00000917690

RefSeq mRNA: 3 — MANE Select: NM_004756 NM_001289979, NM_001289980, NM_004756

CCDS: CCDS12561, CCDS77298

Canonical transcript exons

ENST00000252891 — 10 exons

Exon	Start	End
ENSE00000707432	40669898	40670020
ENSE00000707435	40673344	40673649
ENSE00000842316	40665905	40668138
ENSE00001288231	40690460	40690651
ENSE00003464088	40677232	40677421
ENSE00003482506	40686911	40686995
ENSE00003536340	40680917	40681057
ENSE00003555435	40682894	40682968
ENSE00003560497	40684417	40684556
ENSE00003633140	40682728	40682802

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4813 / max 97.3307, expressed in 1680 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181000	7.6259	1644
180999	2.0980	1112
180998	1.7573	834

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.52	gold quality
buccal mucosa cell	CL:0002336	99.51	gold quality
cardia of stomach	UBERON:0001162	99.45	gold quality
trigeminal ganglion	UBERON:0001675	99.44	gold quality
nipple	UBERON:0002030	99.37	gold quality
trachea	UBERON:0003126	99.34	gold quality
endothelial cell	CL:0000115	99.33	gold quality
pylorus	UBERON:0001166	99.30	gold quality
ventral tegmental area	UBERON:0002691	99.28	silver quality
dorsal root ganglion	UBERON:0000044	99.27	gold quality
medulla oblongata	UBERON:0001896	99.25	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.22	silver quality
subthalamic nucleus	UBERON:0001906	99.22	silver quality
superior vestibular nucleus	UBERON:0007227	99.20	gold quality
inferior vagus X ganglion	UBERON:0005363	99.18	silver quality
superior surface of tongue	UBERON:0007371	99.17	gold quality
lateral globus pallidus	UBERON:0002476	99.15	silver quality
substantia nigra pars reticulata	UBERON:0001966	99.09	silver quality
vena cava	UBERON:0004087	99.06	gold quality
pericardium	UBERON:0002407	99.05	gold quality
urethra	UBERON:0000057	99.03	gold quality
pons	UBERON:0000988	99.01	silver quality
pharyngeal mucosa	UBERON:0000355	99.00	gold quality
substantia nigra pars compacta	UBERON:0001965	99.00	silver quality
thymus	UBERON:0002370	98.97	silver quality
penis	UBERON:0000989	98.95	gold quality
tongue	UBERON:0001723	98.87	gold quality
synovial joint	UBERON:0002217	98.87	gold quality
saphenous vein	UBERON:0007318	98.77	gold quality
body of tongue	UBERON:0011876	98.74	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.12
E-ENAD-17	no	109.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, HNF4A, NEUROD1

miRNA regulators (miRDB)

79 targeting NUMBL, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4687-3P	99.48	66.41	968

Literature-anchored findings (GeneRIF, showing 10)

• Both gene sequence alterations and amplifications of LNX1 and Numbl are present in a subset of human gliomas. (PMID:18940473)
• NUMBL interacts with TRAF6 and promotes the degradation of TRAF6 in vivo, leading to the inhibition of NF-kappaB signaling pathway. (PMID:20079715)
• data suggest that Numbl regulates glioma cell migration and invasion by abrogating TRAF5-induced activation of NF-KappaB (PMID:22593207)
• Numbl-Klf4 signaling is critical to maintain multiple nodes of metastatic progression, including persistence of cancer-initiating cells. (PMID:23440423)
• Numbl might be involved in the inhibition of growth, proliferation, and invasion of 95-D lung cancer cells. (PMID:23681800)
• Numb/Numbl control VEGF receptor endocytosis, signaling, and recycling in endothelial cells, which promotes the angiogenic growth of blood vessels. (PMID:26069237)
• These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis (PMID:27383182)
• NumbL can act as an independent tumor suppressor inhibiting the Notch pathway and regulating the cancer stem cell pool (PMID:27613838)
• investigations revealed that NUMB and NUMBL interacted with small GTPase Rab7 to transition ERBB2 from early to late endosome for degradation. (PMID:28067668)
• SLC8A1 antisense RNA 1 suppresses papillary thyroid cancer malignant progression via the FUS RNA binding protein (FUS)/NUMB like endocytic adaptor protein (Numbl) axis. (PMID:35599603)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	numbl	ENSDARG00000101949
mus_musculus	Numbl	ENSMUSG00000063160
rattus_norvegicus	Numbl	ENSRNOG00000020867
drosophila_melanogaster	Dab	FBGN0000414
drosophila_melanogaster	numb	FBGN0002973
drosophila_melanogaster	CG8312	FBGN0037720
drosophila_melanogaster	Aplip1	FBGN0040281
drosophila_melanogaster	CG42673	FBGN0261555
caenorhabditis_elegans		WBGENE00000894
caenorhabditis_elegans		WBGENE00001116
caenorhabditis_elegans		WBGENE00002176
caenorhabditis_elegans		WBGENE00003830
caenorhabditis_elegans		WBGENE00009930

Paralogs (11): MAPK8IP2 (ENSG00000008735), MAPK8IP1 (ENSG00000121653), NUMB (ENSG00000133961), GULP1 (ENSG00000144366), DAB2 (ENSG00000153071), LDLRAP1 (ENSG00000157978), DAB1 (ENSG00000173406), FAM43B (ENSG00000183114), FAM43A (ENSG00000185112), NOS1AP (ENSG00000198929), C1orf226 (ENSG00000239887)

Protein

Protein identifiers

Numb-like protein — Q9Y6R0 (reviewed: Q9Y6R0)

Alternative names: Numb-related protein

All UniProt accessions (6): Q9Y6R0, A0A0C4DGH3, M0QXQ4, M0QYC2, M0QZV7, M0R0Q4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of embryonic neurogenesis. Also required postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. Negative regulator of NF-kappa-B signaling pathway. The inhibition of NF-kappa-B activation is mediated at least in part, by preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and RIPK1 and by stimulating the ‘Lys-48’-linked polyubiquitination and degradation of TRAF6 in cortical neurons.

Subunit / interactions. Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal). Interacts (via C-terminal) with TRAF6 (via TRAF domains). Associates with EPS15 and NOTCH1.

Subcellular location. Cytoplasm.

Domain organisation. The PTB domain is necessary for the inhibition of MAP3K7IP2-mediated activation of NF-kappa-B.

RefSeq proteins (3): NP_001276908, NP_001276909, NP_004747* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006020	PTB/PI_dom	Domain
IPR010449	Numb_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016698	Numb/numb-like	Family

Pfam: PF00640, PF06311

UniProt features (33 total): compositionally biased region 7, strand 7, modified residue 5, region of interest 5, helix 4, turn 3, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3F0W	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6R0-F1	62.50	0.21

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 (5): 224, 228, 263, 279, 411

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_SYNAPSE_ASSEMBLY, GOBP_RESPONSE_TO_PEPTIDE, GCANCTGNY_MYOD_Q6, AREB6_03, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, TATTATA_MIR374, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, TAL1ALPHAE47_01, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_VENTRICULAR_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03

GO Biological Process (12): nervous system development (GO:0007399), axonogenesis (GO:0007409), cytokine-mediated signaling pathway (GO:0019221), protein metabolic process (GO:0019538), lateral ventricle development (GO:0021670), neuroblast division in subventricular zone (GO:0021849), adherens junction organization (GO:0034332), positive regulation of neurogenesis (GO:0050769), positive regulation of dendrite morphogenesis (GO:0050775), regulation of postsynapse assembly (GO:0150052), neuroblast proliferation (GO:0007405), forebrain development (GO:0030900)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	2
system development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
macromolecule metabolic process	1
primary metabolic process	1
telencephalon development	1
ventricular system development	1
cell proliferation in forebrain	1
neuroblast division	1
cell-cell junction organization	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
positive regulation of cell morphogenesis	1
positive regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
generation of neurons	1
neural precursor cell proliferation	1
brain development	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
synapse	1

Protein interactions and networks

STRING

2168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUMBL	MDM2	Q00987	992
NUMBL	LNX1	Q8TBB1	989
NUMBL	EPS15	P42566	986
NUMBL	DPYSL2	Q16555	946
NUMBL	MSI2	Q96DH6	945
NUMBL	EPS15L1	Q9UBC2	921
NUMBL	NOTCH1	P46531	891
NUMBL	LNX2	Q8N448	873
NUMBL	CDH1	P12830	860
NUMBL	ITCH	Q96J02	815
NUMBL	MSI1	O43347	799
NUMBL	JAG1	P78504	757
NUMBL	NOTCH2	Q04721	745
NUMBL	CDH17	Q12864	736
NUMBL	SH3BP4	Q9P0V3	725

IntAct

102 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
NUMB	SLC1A1	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
SNX9	WASL	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
NUMBL	EGFR	psi-mi:“MI:0407”(direct interaction)	0.570
SPSB3	NUMBL	psi-mi:“MI:0915”(physical association)	0.560
NUMBL	CDK5	psi-mi:“MI:0915”(physical association)	0.560
PIK3R1	NUMBL	psi-mi:“MI:0915”(physical association)	0.560
NUMBL	CLSTN1	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RBFOX1	NUMBL	psi-mi:“MI:0915”(physical association)	0.510
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PSMA3	NUMBL	psi-mi:“MI:0915”(physical association)	0.440

BioGRID (168): SPSB3 (Two-hybrid), NUMBL (Affinity Capture-MS), NUMBL (Affinity Capture-MS), NUMBL (Affinity Capture-MS), NUMBL (Affinity Capture-MS), NUMBL (Proximity Label-MS), NUMBL (Proximity Label-MS), NUMBL (Affinity Capture-MS), NUMBL (Affinity Capture-MS), NUMBL (Affinity Capture-MS), CBY1 (Affinity Capture-MS), NUMBL (Affinity Capture-MS), NUMBL (Affinity Capture-RNA), NUMBL (Affinity Capture-MS), NUMBL (Affinity Capture-Western)

ESM2 similar proteins: A0A0U1RR37, A1L170, A1L1I3, A1L260, A2AMM0, A4IFJ0, B5G1P1, D3ZQL6, E7F5E1, G5BQH4, O08919, O54724, O60237, O75420, P06759, P33622, P53814, P85125, Q2KI85, Q2TAL5, Q3T044, Q3UMT1, Q4RTJ5, Q4V882, Q5I1X5, Q5U2R6, Q63312, Q6NZI2, Q75AS0, Q80VC9, Q8BG95, Q8BGT6, Q8C0J6, Q8CI12, Q8IV56, Q8K382, Q8N3F8, Q8TEH3, Q8WUF5, Q91VJ2

Diamond homologs: A1L1I3, O08919, O88797, P16554, P49757, P98078, P98081, P98082, Q2LC84, Q5PQS4, Q5SW96, Q801G1, Q8C142, Q8K2A1, Q9QZS3, Q9UBP9, Q9XTY6, Q9Y6R0, D3ZAR1, P0C6S7, Q32PV0, Q67FQ3, Q7Z6G8, Q8BIZ1, O75553, P97318, Q8CJH2, Q9BGX5, A5PMU4, O35431, O76337, P59672, P98084, Q5RD33, Q7JUY7, Q92625, Q99767, Q9R237, Q9UQF2, Q9WVI9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	72.6×	3e-11
Activation of BAD and translocation to mitochondria	7	72.0×	5e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	63.5×	1e-09
Activation of BH3-only proteins	7	47.0×	9e-09
RHO GTPases activate PKNs	7	30.0×	2e-07
Intrinsic Pathway for Apoptosis	7	27.7×	3e-07
FOXO-mediated transcription	5	22.7×	7e-05
Apoptosis	9	20.4×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	21.3×	6e-04
obsolete positive regulation of NF-kappaB transcription factor activity	6	14.3×	6e-04
protein autophosphorylation	8	13.5×	1e-04
insulin receptor signaling pathway	5	12.9×	5e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	12.2×	5e-03
intracellular protein localization	8	9.7×	5e-04
regulation of apoptotic process	9	8.7×	4e-04
positive regulation of canonical NF-kappaB signal transduction	8	6.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1154 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40669892:CTTTA:C	donor_loss	1.0000
19:40669893:TTTAC:T	donor_loss	1.0000
19:40669894:TTAC:T	donor_loss	1.0000
19:40669895:TACC:T	donor_loss	1.0000
19:40669896:A:T	donor_loss	1.0000
19:40670016:AGGCA:A	acceptor_gain	1.0000
19:40670017:GGCA:G	acceptor_gain	1.0000
19:40670018:GCA:G	acceptor_gain	1.0000
19:40670019:CA:C	acceptor_gain	1.0000
19:40670019:CAC:C	acceptor_gain	1.0000
19:40670020:AC:A	acceptor_loss	1.0000
19:40670021:C:CC	acceptor_gain	1.0000
19:40670021:C:CG	acceptor_loss	1.0000
19:40673339:CTCA:C	donor_loss	1.0000
19:40673340:TCAC:T	donor_loss	1.0000
19:40673341:CACCT:C	donor_loss	1.0000
19:40673342:AC:A	donor_loss	1.0000
19:40677230:ACCT:A	donor_loss	1.0000
19:40677231:C:CA	donor_loss	1.0000
19:40677231:CCTTT:C	donor_gain	1.0000
19:40677418:CGCC:C	acceptor_gain	1.0000
19:40677420:CC:C	acceptor_gain	1.0000
19:40677421:CCTA:C	acceptor_gain	1.0000
19:40677423:T:A	acceptor_loss	1.0000
19:40680909:ATACT:A	donor_loss	1.0000
19:40680911:A:AC	donor_gain	1.0000
19:40680912:C:CC	donor_gain	1.0000
19:40680913:TCACG:T	donor_loss	1.0000
19:40680914:CAC:C	donor_loss	1.0000
19:40680915:A:AC	donor_gain	1.0000

AlphaMissense

3896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40668050:C:A	W416C	1.000
19:40668050:C:G	W416C	1.000
19:40668052:A:G	W416R	1.000
19:40668052:A:T	W416R	1.000
19:40673408:G:C	S324R	1.000
19:40673408:G:T	S324R	1.000
19:40673410:T:G	S324R	1.000
19:40673423:G:C	F319L	1.000
19:40673423:G:T	F319L	1.000
19:40673424:A:C	F319C	1.000
19:40673424:A:G	F319S	1.000
19:40673425:A:G	F319L	1.000
19:40673454:A:C	F309C	1.000
19:40673463:A:G	F306S	1.000
19:40677305:G:C	F219L	1.000
19:40677305:G:T	F219L	1.000
19:40677306:A:C	F219C	1.000
19:40677306:A:G	F219S	1.000
19:40677307:A:G	F219L	1.000
19:40677365:T:A	K199N	1.000
19:40677365:T:G	K199N	1.000
19:40677366:T:A	K199I	1.000
19:40677367:T:C	K199E	1.000
19:40677369:C:G	R198P	1.000
19:40677375:A:G	L196P	1.000
19:40677375:A:T	L196Q	1.000
19:40677377:G:C	C195W	1.000
19:40677378:C:T	C195Y	1.000
19:40677379:A:G	C195R	1.000
19:40677384:G:T	A193D	1.000

dbSNP variants (sampled 300 via entrez): RS1000007368 (19:40677066 G>A), RS1000049364 (19:40689042 C>A), RS1000066245 (19:40671885 ATT>A,AT,ATTT), RS1000120456 (19:40666131 TAGA>T), RS1000123169 (19:40676875 C>A,T), RS1000314235 (19:40688897 C>G,T), RS1000325848 (19:40690396 A>C,G,T), RS1000430355 (19:40688544 T>C,G), RS1000505614 (19:40688683 T>C), RS1000534172 (19:40687662 T>C), RS1000965576 (19:40672687 G>A), RS1001019367 (19:40672997 T>C), RS1001187196 (19:40684161 C>T), RS1001193103 (19:40678352 G>A), RS1001197720 (19:40679132 G>A,T)

Disease associations

OMIM: gene MIM:604018 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001455_1	Kawasaki disease	4.000000e-10
GCST003847_2	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) level)	6.000000e-08
GCST003849_1	Caffeine metabolism (plasma 3,7-dimethylxanthine (theobromine) level)	4.000000e-06
GCST003851_10	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_11	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	8.000000e-09
GCST003851_12	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-10
GCST003851_13	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-22
GCST003851_14	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-10
GCST003851_15	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-11
GCST003851_16	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_17	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-11
GCST003851_18	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_19	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-11
GCST003851_20	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_21	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-09
GCST003851_22	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-08
GCST003851_23	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-08
GCST003851_26	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_27	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_9	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	6.000000e-09
GCST004744_18	Lung adenocarcinoma	7.000000e-06
GCST004748_8	Lung cancer	2.000000e-07
GCST009921_7	Carotid intima media thickness (mean)	1.000000e-10
GCST012420_1	tricyclic pyrone compound response (IC50)	4.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007872	caffeine metabolite measurement
EFO:0600033	response to mitochondrial complex I inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Valproic Acid	affects expression, increases methylation	2
Cadmium Chloride	increases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric chloride	increases expression	1
perfluorodecanoic acid	decreases expression	1
abrine	decreases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Naphthoquinones	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7W9	Ubigene A-549 NUMBL KO	Cancer cell line	Male
CVCL_D8RS	Ubigene HCT 116 NUMBL KO	Cancer cell line	Male
CVCL_D9LT	Ubigene HEK293 NUMBL KO	Transformed cell line	Female
CVCL_E0JF	Ubigene HeLa NUMBL KO	Cancer cell line	Female

Clinical trials (associated diseases)

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