RIN3

Summary

RIN3 (Ras and Rab interactor 3, HGNC:18751) is a protein-coding gene on chromosome 14q32.12, encoding Ras and Rab interactor 3 (Q8TB24). Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP.

Summary: This protein encoded by this gene is a member of the RIN family of Ras interaction-interference proteins, which are binding partners to the RAB5 small GTPases. The protein functions as a guanine nucleotide exchange for RAB5B and RAB31. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79890 — RefSeq curated summary.

At a glance

• GWAS associations: 105
• Clinical variants (ClinVar): 150 total
• MANE Select transcript: NM_024832

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18751
Approved symbol	RIN3
Name	Ras and Rab interactor 3
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22439
Ensembl gene	ENSG00000100599
Ensembl biotype	protein_coding
OMIM	610223
Entrez	79890

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000216487, ENST00000418924, ENST00000553959, ENST00000553992, ENST00000554888, ENST00000555589, ENST00000555891, ENST00000555908, ENST00000556385, ENST00000556418, ENST00000557762, ENST00000620541, ENST00000863458, ENST00000863459

RefSeq mRNA: 2 — MANE Select: NM_024832 NM_001319987, NM_024832

CCDS: CCDS32144

Canonical transcript exons

ENST00000216487 — 10 exons

Exon	Start	End
ENSE00001380171	92555751	92555955
ENSE00001411518	92513781	92513976
ENSE00002518598	92687926	92688994
ENSE00003484538	92651582	92653075
ENSE00003490838	92659161	92659469
ENSE00003565230	92676475	92676606
ENSE00003572694	92684987	92685150
ENSE00003592679	92641238	92641329
ENSE00003657033	92577360	92577477
ENSE00003687523	92615407	92615479

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 96.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5332 / max 1220.2855, expressed in 1669 samples.

FANTOM5 promoters (23 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141104	12.1422	1630
141116	3.8732	282
141125	2.2327	355
141124	1.6042	338
141130	1.4541	326
141100	0.7522	522
141121	0.7117	144
141118	0.6048	170
141115	0.5836	151
141101	0.5818	349

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.54	gold quality
monocyte	CL:0000576	95.14	gold quality
leukocyte	CL:0000738	95.14	gold quality
mononuclear cell	CL:0000842	95.04	gold quality
blood	UBERON:0000178	94.42	gold quality
spleen	UBERON:0002106	91.47	gold quality
bone marrow cell	CL:0002092	89.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.45	gold quality
right lung	UBERON:0002167	88.75	gold quality
apex of heart	UBERON:0002098	88.10	gold quality
upper lobe of left lung	UBERON:0008952	87.82	gold quality
ascending aorta	UBERON:0001496	87.49	gold quality
thoracic aorta	UBERON:0001515	87.44	gold quality
tendon of biceps brachii	UBERON:0008188	87.04	gold quality
left adrenal gland	UBERON:0001234	86.96	gold quality
upper lobe of lung	UBERON:0008948	86.96	gold quality
left adrenal gland cortex	UBERON:0035825	86.92	gold quality
descending thoracic aorta	UBERON:0002345	86.77	gold quality
right adrenal gland	UBERON:0001233	86.66	gold quality
right coronary artery	UBERON:0001625	86.63	gold quality
right adrenal gland cortex	UBERON:0035827	86.16	gold quality
buccal mucosa cell	CL:0002336	85.97	gold quality
right lobe of liver	UBERON:0001114	85.93	gold quality
right testis	UBERON:0004534	85.61	gold quality
adrenal cortex	UBERON:0001235	85.43	gold quality
left testis	UBERON:0004533	85.26	gold quality
bone marrow	UBERON:0002371	85.16	gold quality
left uterine tube	UBERON:0001303	84.88	gold quality
mucosa of transverse colon	UBERON:0004991	84.78	gold quality
adrenal gland	UBERON:0002369	84.73	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.40
E-MTAB-9067	yes	11.46
E-MTAB-9388	yes	10.57
E-CURD-119	yes	5.96
E-MTAB-7606	no	154.22
E-CURD-112	no	2.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting RIN3, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-3158-3P	98.45	64.25	560
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-564	95.85	65.01	163
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-4633-3P	93.85	63.56	534
HSA-MIR-668-5P	90.24	59.97	79
HSA-MIR-3195	88.05	57.43	53

Literature-anchored findings (GeneRIF, showing 10)

• RIN3 biochemically characterized as the stimulator and stabilizer for GTP-Rab5 plays an important role in the transport pathway from plasma membrane to early endosomes (PMID:12972505)
• Tyrosine-phosphorylation signals are involved in the RIN3 activation and translocation to early endocytic vesicles. (PMID:18486601)
• RIN3 specifically acts as a GEF for Rab31. (PMID:21586568)
• RIN3 is a negative regulator of mast cell responses to SCF (PMID:23185384)
• The study reports a novel association between a variant within RIN3 and lower limb-bone mineral density and note its previous association with risk of Paget’s disease. (PMID:24945404)
• RIN3 may contribute to Paget’s disease of bone susceptibility by affecting osteoclast function. (PMID:25701875)
• discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3 (PMID:26296892)
• RIN3 may be involved in endolysosomal transport-a process known to be important to development of early onset AD. (PMID:28738127)
• Genetic Variation in RIN3 in the Belgian Population Supports Its Involvement in the Pathogenesis of Paget’s Disease of Bone and Modifies the Age of Onset. (PMID:30726512)
• The neuronal-specific isoform of BIN1 regulates beta-secretase cleavage of APP and Abeta generation in a RIN3-dependent manner. (PMID:35241726)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rin3	ENSDARG00000077618
mus_musculus	Rin3	ENSMUSG00000044456
rattus_norvegicus	Rin3	ENSRNOG00000007062
drosophila_melanogaster	spri	FBGN0085443
drosophila_melanogaster	Rabex-5	FBGN0262937
caenorhabditis_elegans		WBGENE00008183
caenorhabditis_elegans		WBGENE00012644

Paralogs (6): VPS9D1 (ENSG00000075399), RIN2 (ENSG00000132669), RABGEF1 (ENSG00000154710), GAPVD1 (ENSG00000165219), RIN1 (ENSG00000174791), RINL (ENSG00000187994)

Protein

Protein identifiers

Ras and Rab interactor 3 — Q8TB24 (reviewed: Q8TB24)

Alternative names: Ras interaction/interference protein 3

All UniProt accessions (5): Q8TB24, A0A087WWY9, G3V2I7, G3V534, H0YJ83

UniProt curated annotations — full annotation on UniProt →

Function. Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP. Required for normal RAB31 function.

Subunit / interactions. Interacts with CD2AP, RAB5B, RAB31 and BIN1.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Early endosome.

Tissue specificity. Widely expressed.

Similarity. Belongs to the RIN (Ras interaction/interference) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TB24-1	1	yes
Q8TB24-4	4

RefSeq proteins (2): NP_001306916, NP_079108* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000980	SH2	Domain
IPR003123	VPS9	Domain
IPR035869	RIN3_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037191	VPS9_dom_sf	Homologous_superfamily
IPR045046	Vps9-like	Family

Pfam: PF02204, PF23268

UniProt features (26 total): sequence variant 7, region of interest 5, compositionally biased region 4, domain 3, splice variant 2, mutagenesis site 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3U23	X-RAY DIFFRACTION	1.11
4WCI	X-RAY DIFFRACTION	1.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TB24-F1	62.47	0.23

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
825	strongly reduced guanine nucleotide exchange factor activity toward rab31; when associated with a-828.
828	strongly reduced guanine nucleotide exchange factor activity toward rab31; when associated with a-825.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 230 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE

GO Biological Process (6): negative regulation of receptor internalization (GO:0002091), endocytosis (GO:0006897), signal transduction (GO:0007165), negative regulation of mast cell chemotaxis (GO:0060755), regulation of vesicle size (GO:0097494), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (10): cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), endocytic vesicle (GO:0030139), axon (GO:0030424), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982), neuronal cell body (GO:0043025), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
GTPase regulator activity	2
cellular anatomical structure	2
cytoplasm	2
cytoplasmic vesicle	2
neuron projection	2
regulation of receptor internalization	1
receptor internalization	1
negative regulation of receptor-mediated endocytosis	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
mast cell chemotaxis	1
negative regulation of leukocyte chemotaxis	1
regulation of mast cell chemotaxis	1
regulation of cellular component size	1
transport	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
endosome	1
dendritic tree	1
intracellular vesicle	1
membrane-bounded organelle	1
somatodendritic compartment	1
cell body	1
endomembrane system	1

Protein interactions and networks

STRING

2166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIN3	BIN1	O00499	996
RIN3	RAB5B	P35239	837
RIN3	RAB5A	P20339	826
RIN3	SLC24A4	Q8NFF2	819
RIN3	CASS4	Q9NQ75	729
RIN3	NME8	Q8N427	723
RIN3	ZCWPW1	Q9H0M4	720
RIN3	SORL1	Q92673	680
RIN3	FERMT2	Q96AC1	677
RIN3	PICALM	Q13492	673
RIN3	ABCA7	Q8IZY2	667
RIN3	CD2AP	Q9Y5K6	662
RIN3	MS4A6A	Q9H2W1	623
RIN3	HLA-DRB5	Q30154	621
RIN3	CELF1	Q92879	620

IntAct

67 interactions, top by confidence:

A	B	Type	Score
RIN3	BIN1	psi-mi:“MI:0915”(physical association)	0.790
BIN1	RIN3	psi-mi:“MI:0915”(physical association)	0.790
RIN3	PLCG1	psi-mi:“MI:0915”(physical association)	0.600
PLCG1	RIN3	psi-mi:“MI:0407”(direct interaction)	0.600
CRK	RIN3	psi-mi:“MI:0915”(physical association)	0.570
RIN3	CRK	psi-mi:“MI:0915”(physical association)	0.570
RIN3	CD2AP	psi-mi:“MI:0915”(physical association)	0.570
CD2AP	RIN3	psi-mi:“MI:0915”(physical association)	0.570
RIN3	CRKL	psi-mi:“MI:0915”(physical association)	0.550
BIN1	SMCHD1	psi-mi:“MI:0914”(association)	0.550
STK16	UNC119B	psi-mi:“MI:0914”(association)	0.530
ABL1	RIN3	psi-mi:“MI:0915”(physical association)	0.400
SRC	RIN3	psi-mi:“MI:0915”(physical association)	0.400
RIN3	FYN	psi-mi:“MI:0915”(physical association)	0.400
RIN3	GRB2	psi-mi:“MI:0915”(physical association)	0.400
RIN3	NCK1	psi-mi:“MI:0915”(physical association)	0.400
KCTD17	RIN3	psi-mi:“MI:0915”(physical association)	0.370
CYP46A1	RIN3	psi-mi:“MI:0915”(physical association)	0.370
RIN3	ASB3	psi-mi:“MI:0915”(physical association)	0.370
RIN3	ZNF639	psi-mi:“MI:0915”(physical association)	0.370
ZNF71	RIN3	psi-mi:“MI:0915”(physical association)	0.370
ASB8	RIN3	psi-mi:“MI:0915”(physical association)	0.370
RIN3	EPS8L2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (473): RAB5B (Two-hybrid), ASB8 (Two-hybrid), DOK3 (Two-hybrid), FAM127C (Two-hybrid), MPEG1 (Two-hybrid), PLB1 (Two-hybrid), SPATA12 (Two-hybrid), SPRY4 (Two-hybrid), TM4SF19 (Two-hybrid), TSSK3 (Two-hybrid), ASB3 (Two-hybrid), CRK (Two-hybrid), CRKL (Two-hybrid), CSRP3 (Two-hybrid), CYP2C8 (Two-hybrid)

ESM2 similar proteins: A0A8M9QN10, A1BPI0, A2ARM1, A2CI97, A2CI98, A2CJ06, C9JE40, O15055, O43147, O54943, O70173, O70303, O70361, O95238, P0C2N6, P0C6P5, P56645, P59025, P59729, P97433, Q0P4K8, Q3TD16, Q5EB20, Q5PQS0, Q5SSZ5, Q5VUB5, Q6IRN0, Q6P4K6, Q76I79, Q7TSI1, Q80TQ5, Q80UW3, Q810F8, Q8C8C1, Q8CCC3, Q8CJE2, Q8N1W1, Q8ND61, Q8TB24, Q8WWF5

Diamond homologs: A2RV61, A5D794, A8WVM4, P59729, Q10NQ3, Q14C86, Q6PAR5, Q8TB24, Q9GYH7, Q9LT31, O74396, P54787, Q8WYP3, Q9D684, Q9JM13, P97680, Q13671, Q6ZS11, Q80UW3, Q921Q7, O18973, Q8MQW8, Q9UJ41, Q29HW3, Q9VZ08

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
Downstream signal transduction	6	67.2×	1e-07
DAP12 signaling	5	54.2×	4e-06
Signaling by SCF-KIT	5	36.5×	2e-05
FCGR3A-mediated phagocytosis	6	33.0×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	37.4×	1e-04
cellular response to transforming growth factor beta stimulus	5	30.0×	1e-04
T cell receptor signaling pathway	6	19.8×	1e-04
intracellular signal transduction	7	5.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2769 predictions. Top by Δscore:

Variant	Effect	Δscore
14:92513974:GGG:G	donor_gain	1.0000
14:92513975:GGG:G	donor_gain	1.0000
14:92555749:AGTCC:A	acceptor_gain	1.0000
14:92555750:GT:G	acceptor_gain	1.0000
14:92555750:GTCCG:G	acceptor_gain	1.0000
14:92555902:C:G	donor_gain	1.0000
14:92555946:G:GA	donor_gain	1.0000
14:92555953:GGG:G	donor_gain	1.0000
14:92555954:GGG:G	donor_gain	1.0000
14:92577359:GAT:G	acceptor_gain	1.0000
14:92577465:G:GT	donor_gain	1.0000
14:92577473:GTCGA:G	donor_gain	1.0000
14:92577474:TCGA:T	donor_gain	1.0000
14:92577475:CGA:C	donor_gain	1.0000
14:92577476:GA:G	donor_gain	1.0000
14:92577476:GAG:G	donor_gain	1.0000
14:92577477:AGTA:A	donor_loss	1.0000
14:92577478:G:GG	donor_gain	1.0000
14:92577479:TAA:T	donor_loss	1.0000
14:92641237:GA:G	acceptor_gain	1.0000
14:92641327:TGGG:T	donor_loss	1.0000
14:92641329:GGTG:G	donor_loss	1.0000
14:92641330:G:GG	donor_gain	1.0000
14:92641330:GT:G	donor_loss	1.0000
14:92641331:T:A	donor_loss	1.0000
14:92641332:GAGTC:G	donor_loss	1.0000
14:92644512:G:GT	donor_gain	1.0000
14:92659159:A:AC	acceptor_loss	1.0000
14:92659159:A:AG	acceptor_gain	1.0000
14:92659160:G:GA	acceptor_gain	1.0000

AlphaMissense

6397 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:92676577:T:C	L813P	1.000
14:92685097:T:A	W860R	1.000
14:92685097:T:C	W860R	1.000
14:92685099:G:C	W860C	1.000
14:92685099:G:T	W860C	1.000
14:92652971:T:C	L641P	0.999
14:92652983:G:C	R645P	0.999
14:92653001:T:C	L651P	0.999
14:92653013:T:C	L655P	0.999
14:92676499:T:C	F787S	0.999
14:92676511:T:C	L791P	0.999
14:92684999:T:C	L827P	0.999
14:92688126:G:C	K944N	0.999
14:92688126:G:T	K944N	0.999
14:92688167:T:C	F958S	0.999
14:92659197:T:C	L688P	0.998
14:92659335:C:A	P734Q	0.998
14:92659335:C:G	P734R	0.998
14:92659398:C:A	P755H	0.998
14:92659419:T:C	L762P	0.998
14:92659422:T:C	L763P	0.998
14:92676498:T:C	F787L	0.998
14:92676500:C:A	F787L	0.998
14:92676500:C:G	F787L	0.998
14:92676502:T:C	L788P	0.998
14:92676573:G:A	E812K	0.998
14:92684992:T:C	Y825H	0.998
14:92684995:T:G	Y826D	0.998
14:92685098:G:C	W860S	0.998
14:92685107:G:C	R863P	0.998

dbSNP variants (sampled 300 via entrez): RS1000056491 (14:92555588 C>T), RS1000058754 (14:92664666 G>A), RS1000068036 (14:92515903 G>A), RS1000106070 (14:92578439 C>T), RS1000146737 (14:92671359 G>A), RS1000148059 (14:92629165 G>A,C), RS1000166496 (14:92657124 C>T), RS1000188517 (14:92523611 C>T), RS1000188754 (14:92680940 CCT>C), RS1000198021 (14:92602504 G>C), RS1000213084 (14:92542383 T>C,G), RS1000239960 (14:92642067 G>A,T), RS1000244578 (14:92581087 A>T), RS1000255215 (14:92620977 T>A), RS1000268072 (14:92671137 G>A,T)

Disease associations

OMIM: gene MIM:610223 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096)

Orphanet (1): NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

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

GWAS associations

105 associations (top):

Study	Trait	p-value
GCST001066_12	Dialysis-related mortality	8.000000e-06
GCST001086_5	Paget’s disease	3.000000e-11
GCST002245_20	Alzheimer’s disease (late onset)	6.000000e-09
GCST002350_4	Chronic obstructive pulmonary disease (severe)	7.000000e-08
GCST002351_4	Chronic obstructive pulmonary disease (moderate to severe)	5.000000e-09
GCST002492_11	Bone mineral density (paediatric, lower limb)	2.000000e-09
GCST002492_3	Bone mineral density (paediatric, lower limb)	1.000000e-10
GCST002494_14	Bone mineral density (paediatric, total body less head)	5.000000e-08
GCST002494_7	Bone mineral density (paediatric, total body less head)	3.000000e-09
GCST002525_12	Local histogram emphysema pattern	2.000000e-07
GCST002525_13	Local histogram emphysema pattern	3.000000e-07
GCST002795_4	Chronic obstructive pulmonary disease	1.000000e-06
GCST003262_126	Post bronchodilator FEV1	3.000000e-06
GCST003264_1282	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_1283	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_1284	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST003264_1285	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST003264_1286	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST003264_1290	Post bronchodilator FEV1/FVC ratio	8.000000e-07
GCST003264_1578	Post bronchodilator FEV1/FVC ratio	9.000000e-08
GCST003264_1579	Post bronchodilator FEV1/FVC ratio	1.000000e-07
GCST003264_1580	Post bronchodilator FEV1/FVC ratio	1.000000e-07
GCST003264_1581	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_292	Post bronchodilator FEV1/FVC ratio	7.000000e-08
GCST003264_304	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_517	Post bronchodilator FEV1/FVC ratio	9.000000e-08
GCST003264_518	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003264_540	Post bronchodilator FEV1/FVC ratio	6.000000e-09
GCST003264_547	Post bronchodilator FEV1/FVC ratio	1.000000e-07
GCST003264_548	Post bronchodilator FEV1/FVC ratio	1.000000e-07

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0005850	emphysema pattern measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005763	pulse pressure measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0004312	vital capacity
EFO:0004352	mortality
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007984	platelet component distribution width
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
(+)-JQ1 compound	decreases expression	3
Benzo(a)pyrene	decreases expression, increases mutagenesis, affects methylation	3
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Amiodarone	increases expression	1
Arsenic	increases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00126581	PHASE2	COMPLETED	Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT00368992	PHASE2	COMPLETED	S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
NCT00511485	PHASE2	COMPLETED	Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03)
NCT00950365	PHASE2	COMPLETED	Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer
NCT00955305	PHASE2	TERMINATED	Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
NCT01218516	PHASE2	COMPLETED	A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung
NCT01294306	PHASE2	COMPLETED	MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy
NCT01557959	PHASE2	COMPLETED	Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
NCT01561456	PHASE2	COMPLETED	Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung
NCT01578551	PHASE2	TERMINATED	Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma.
NCT01578668	PHASE2	COMPLETED	Erlotinib Plus Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases
NCT01819428	PHASE2	TERMINATED	NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma
NCT01935336	PHASE2	COMPLETED	Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
NCT02134912	PHASE2	TERMINATED	S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib
NCT02186847	PHASE2	COMPLETED	Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer