ARHGAP42

Summary

ARHGAP42 (Rho GTPase activating protein 42, HGNC:26545) is a protein-coding gene on chromosome 11q22.1, encoding Rho GTPase-activating protein 42 (A6NI28). May influence blood pressure by functioning as a GTPase-activating protein for RHOA in vascular smooth muscle.

This gene encodes a Rho GTPase-activating protein (RhoGAP), and member of the GRAF or BAR-PH family of proteins. Expression of this gene is enriched in vascular smooth muscle cells and the encoded protein inhibits RhoA activity to regulate vascular tone and control blood pressure. A mutation in the first intron of this gene modulates its expression and is associated with reduced blood pressure in human patients with borderline hypertension.

Source: NCBI Gene 143872 — RefSeq curated summary.

At a glance

• Gene–disease (curated): interstitial lung disease (Limited, GenCC)
• GWAS associations: 85
• Clinical variants (ClinVar): 140 total — 1 likely-pathogenic
• MANE Select transcript: NM_152432

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26545
Approved symbol	ARHGAP42
Name	Rho GTPase activating protein 42
Location	11q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32810, GRAF3, AD031
Ensembl gene	ENSG00000165895
Ensembl biotype	protein_coding
OMIM	615936
Entrez	143872

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000298815, ENST00000303130, ENST00000524649, ENST00000524892, ENST00000525558, ENST00000529406, ENST00000529535, ENST00000531183, ENST00000534060

RefSeq mRNA: 2 — MANE Select: NM_152432 NM_001367945, NM_152432

Canonical transcript exons

ENST00000298815 — 24 exons

Exon	Start	End
ENSE00002294094	100687288	100687832
ENSE00002507325	100913452	100913553
ENSE00003535435	100859554	100859625
ENSE00003551388	100987513	100987592
ENSE00003609823	100795105	100795166
ENSE00003639017	100770343	100770438
ENSE00003888938	100961684	100961768
ENSE00003889364	100933156	100933260
ENSE00003889519	100978987	100979049
ENSE00003889711	100976815	100976971
ENSE00003890722	100948457	100948535
ENSE00003891689	100921494	100921604
ENSE00003892089	100959883	100959945
ENSE00003892439	100988713	100993941
ENSE00003892762	100976057	100976437
ENSE00003892853	100962409	100962467
ENSE00003892981	100943759	100943868
ENSE00003893520	100974459	100974603
ENSE00003894769	100941784	100941884
ENSE00003895405	100965671	100965776
ENSE00003895548	100960915	100960989
ENSE00003896060	100973175	100973334
ENSE00003896131	100949917	100949956
ENSE00003896246	100936203	100936332

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 94.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6777 / max 154.4054, expressed in 1334 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116360	4.7609	1102
116359	2.0103	854
116361	0.5265	330
116358	0.3762	225
116367	0.0038	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.58	gold quality
jejunal mucosa	UBERON:0000399	91.69	gold quality
sural nerve	UBERON:0015488	91.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.86	gold quality
adrenal tissue	UBERON:0018303	87.67	gold quality
epithelial cell of pancreas	CL:0000083	86.30	silver quality
pigmented layer of retina	UBERON:0001782	86.00	gold quality
retina	UBERON:0000966	85.98	gold quality
placenta	UBERON:0001987	85.72	gold quality
bronchial epithelial cell	CL:0002328	84.68	gold quality
tibial nerve	UBERON:0001323	83.92	gold quality
bronchus	UBERON:0002185	83.27	gold quality
tendon	UBERON:0000043	83.07	gold quality
colonic mucosa	UBERON:0000317	81.53	gold quality
right lung	UBERON:0002167	81.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.93	gold quality
colonic epithelium	UBERON:0000397	80.84	gold quality
ileal mucosa	UBERON:0000331	80.81	gold quality
kidney epithelium	UBERON:0004819	80.50	silver quality
duodenum	UBERON:0002114	79.62	gold quality
lung	UBERON:0002048	79.53	gold quality
subcutaneous adipose tissue	UBERON:0002190	79.46	gold quality
gall bladder	UBERON:0002110	79.38	gold quality
endocervix	UBERON:0000458	79.30	gold quality
right lobe of liver	UBERON:0001114	79.18	gold quality
liver	UBERON:0002107	79.15	gold quality
mucosa of transverse colon	UBERON:0004991	78.76	gold quality
rectum	UBERON:0001052	78.70	gold quality
metanephros cortex	UBERON:0010533	78.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	12.55
E-HCAD-35	yes	9.62
E-ANND-3	yes	6.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting ARHGAP42, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548A-5P	99.94	71.27	3482

Literature-anchored findings (GeneRIF, showing 7)

• The smooth muscle-selective GRAF3 is a critical regulator of vascular tone and hypertension. (PMID:24335996)
• Blood pressure-associated polymorphism controls ARHGAP42 expression via serum response factor DNA binding (PMID:28112683)
• GRAF3 serves as a blood volume-sensitive rheostat to control smooth muscle contractility and blood pressure. (PMID:29099324)
• A decreased expression level of Rho GTPase-activating protein 42 gene (ARHGAP42) mRNA in the blood was found in the translocation carriers relative to controls. (PMID:30903111)
• ARHGAP42 expression was inhibited by micro-RNA 505 (miR505) which interacted with the ARHGAP42 3’-untranslated region (UTR) to facilitate its degradation and by AK124326, a long noncoding RNA that overlaps with the ARHGAP42 transcription start site on the opposite DNA strand (PMID:31886719)
• Maternal Hypertension-Related Genotypes and Congenital Heart Defects. (PMID:32710738)
• A homozygous stop-gain variant in ARHGAP42 is associated with childhood interstitial lung disease, systemic hypertension, and immunological findings. (PMID:34232960)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap42b	ENSDARG00000010654
danio_rerio	arhgap42a	ENSDARG00000056619
mus_musculus	Arhgap42	ENSMUSG00000050730
rattus_norvegicus	Arhgap42	ENSRNOG00000026821
drosophila_melanogaster	Graf	FBGN0030685
caenorhabditis_elegans		WBGENE00020209

Paralogs (3): ARHGAP10 (ENSG00000071205), OPHN1 (ENSG00000079482), ARHGAP26 (ENSG00000145819)

Protein

Protein identifiers

Rho GTPase-activating protein 42 — A6NI28 (reviewed: A6NI28)

Alternative names: Rho GTPase-activating protein 10-like, Rho-type GTPase-activating protein 42

All UniProt accessions (5): A0A499FIA2, A6NI28, E9PJK4, H0YDU1, H0YEJ7

UniProt curated annotations — full annotation on UniProt →

Function. May influence blood pressure by functioning as a GTPase-activating protein for RHOA in vascular smooth muscle.

Tissue specificity. Highly and selectively expressed in smooth muscle cells.

RefSeq proteins (2): NP_001354874, NP_689645* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR004148	BAR_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR047225	PH_GRAF	Domain
IPR047234	GRAF_fam	Family

Pfam: PF00169, PF00620, PF14604, PF16746

UniProt features (26 total): modified residue 7, compositionally biased region 5, sequence conflict 5, domain 4, region of interest 2, chain 1, site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NI28-F1	75.04	0.48

Functional residue map

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

Catalytic / active sites (1): 417 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (7): 376, 683, 740, 753, 756, 811, 870

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle

MSigDB gene sets: 158 (showing top): GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, WHITEHURST_PACLITAXEL_SENSITIVITY, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, chr11q22, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY

GO Biological Process (5): negative regulation of systemic arterial blood pressure (GO:0003085), signal transduction (GO:0007165), negative regulation of Rho protein signal transduction (GO:0035024), activation of GTPase activity (GO:0090630), negative regulation of vascular associated smooth muscle contraction (GO:1904694)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	5

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of systemic arterial blood pressure	1
negative regulation of blood pressure	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
positive regulation of GTPase activity	1
regulation of vascular associated smooth muscle contraction	1
vascular associated smooth muscle contraction	1
negative regulation of vasoconstriction	1
negative regulation of smooth muscle contraction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

722 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP42	KRTAP20-4	Q3LI62	710
ARHGAP42	MAIP1	Q8WWC4	521
ARHGAP42	C2orf80	Q0P641	513
ARHGAP42	MGAT4D	A6NG13	509
ARHGAP42	RMP64	Q6NW34	489
ARHGAP42	VPS33B	Q9H267	474
ARHGAP42	PPP1R10	Q96QC0	461
ARHGAP42	ARHGEF37	A1IGU5	456
ARHGAP42	GFOD1	Q9NXC2	456
ARHGAP42	STOX2	Q9P2F5	451
ARHGAP42	PRSS56	P0CW18	430
ARHGAP42	ASCL4	Q6XD76	429
ARHGAP42	SRF	P11831	428
ARHGAP42	MEIOC	A2RUB1	419
ARHGAP42	UVSSA	Q2YD98	419

IntAct

14 interactions, top by confidence:

A	B	Type	Score
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
ARHGAP26	ARHGAP10	psi-mi:“MI:0914”(association)	0.510
ARHGAP26	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
DENND2C	ARHGAP42	psi-mi:“MI:0914”(association)	0.350
ARHGAP42	APOD	psi-mi:“MI:0914”(association)	0.350
GCH1	ARHGAP42	psi-mi:“MI:0914”(association)	0.350
CRKL	ARHGAP42	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): ARHGAP42 (Affinity Capture-MS), ARHGAP42 (Affinity Capture-MS), ARHGAP42 (Affinity Capture-MS), ARHGAP42 (Affinity Capture-MS), ARHGAP42 (Affinity Capture-MS), ARHGAP42 (Affinity Capture-MS), ARHGAP42 (Affinity Capture-MS), ARHGAP42 (Affinity Capture-RNA), ARHGAP42 (Affinity Capture-MS), APOD (Affinity Capture-MS), DEK (Affinity Capture-MS), TMEM57 (Affinity Capture-MS), BTF3 (Affinity Capture-MS), NACA (Affinity Capture-MS), NEFL (Affinity Capture-MS)

ESM2 similar proteins: A0JM95, A1A4S6, A2A2Y4, A4II46, A4IJ06, A6NI28, B2RQE8, B5DFQ4, F1LVW7, O60879, O60890, O70566, O95267, P0C7A6, P0CAX5, Q02384, Q07889, Q07890, Q08DP6, Q0P4Q4, Q28EC1, Q4V7P7, Q566W7, Q5R6F6, Q5R803, Q5U4T3, Q62245, Q69ZK0, Q6DBW1, Q6DHR3, Q6NTL4, Q6PCS4, Q6Y5D8, Q6ZM89, Q7YQL5, Q7YQL6, Q8AVG0, Q8BHD4, Q8IV61, Q8N9B8

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6NI28, A6QNS3, A7YY57, A8WRJ2, B2RQE8, B5DFQ4, D3ZFJ3, F1LQX4, F1LXF1, O14559, O60890, O74360, O94466, P0CAX5, P11274, P15882, P30337, P34288, P46941, P52757, P55194, P81128, P83509, P97393, Q03070, Q08DP6, Q12979, Q13017, Q13459, Q15311, Q17QN0, Q17R89, Q20498, Q52LW3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PTK2	“up-regulates activity”	ARHGAP42	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	117
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599287	t(11;18)(q11.2;q12.2)	Likely pathogenic

SpliceAI

5321 predictions. Top by Δscore:

Variant	Effect	Δscore
11:100687790:G:GT	donor_gain	1.0000
11:100687802:G:GT	donor_gain	1.0000
11:100687828:GAGGA:G	donor_gain	1.0000
11:100687830:GGA:G	donor_gain	1.0000
11:100687831:GA:G	donor_gain	1.0000
11:100687831:GAG:G	donor_gain	1.0000
11:100687833:G:GG	donor_gain	1.0000
11:100770335:A:AG	acceptor_gain	1.0000
11:100770434:TATTG:T	donor_gain	1.0000
11:100770435:ATTG:A	donor_gain	1.0000
11:100770436:TTG:T	donor_gain	1.0000
11:100770437:TG:T	donor_gain	1.0000
11:100770437:TGGT:T	donor_loss	1.0000
11:100770438:GG:G	donor_gain	1.0000
11:100770439:G:GA	donor_loss	1.0000
11:100770439:G:GG	donor_gain	1.0000
11:100770440:TAA:T	donor_loss	1.0000
11:100770441:AA:A	donor_loss	1.0000
11:100793254:A:T	donor_gain	1.0000
11:100795091:A:AG	acceptor_gain	1.0000
11:100795092:T:G	acceptor_gain	1.0000
11:100795099:A:AG	acceptor_gain	1.0000
11:100795100:A:G	acceptor_gain	1.0000
11:100795101:A:AG	acceptor_gain	1.0000
11:100795102:C:G	acceptor_gain	1.0000
11:100795103:A:AG	acceptor_gain	1.0000
11:100795103:A:AT	acceptor_loss	1.0000
11:100795103:AGCT:A	acceptor_gain	1.0000
11:100795104:G:GA	acceptor_gain	1.0000
11:100795104:GC:G	acceptor_gain	1.0000

AlphaMissense

5750 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:100687700:T:C	F8L	1.000
11:100687702:C:A	F8L	1.000
11:100687702:C:G	F8L	1.000
11:100687764:T:C	L29P	1.000
11:100687789:G:C	K37N	1.000
11:100687789:G:T	K37N	1.000
11:100687794:T:C	L39P	1.000
11:100687806:G:A	G43D	1.000
11:100687815:T:C	L46P	1.000
11:100770346:T:C	L53P	1.000
11:100770367:T:C	F60S	1.000
11:100770379:T:C	L64S	1.000
11:100770394:T:C	F69S	1.000
11:100795156:G:C	R101T	1.000
11:100795156:G:T	R101M	1.000
11:100795157:G:C	R101S	1.000
11:100795157:G:T	R101S	1.000
11:100859576:T:C	L112S	1.000
11:100859588:T:A	L116H	1.000
11:100859588:T:C	L116P	1.000
11:100859596:T:C	F119L	1.000
11:100859597:T:C	F119S	1.000
11:100859598:T:A	F119L	1.000
11:100859598:T:G	F119L	1.000
11:100859600:G:C	R120P	1.000
11:100921587:T:C	F194L	1.000
11:100921589:T:A	F194L	1.000
11:100921589:T:G	F194L	1.000
11:100921597:T:A	V197D	1.000
11:100933169:T:C	L204P	1.000

dbSNP variants (sampled 300 via entrez): RS1000004019 (11:100940210 GAAAA>G,GAAAAA), RS1000006502 (11:100982954 G>A), RS1000029188 (11:100921965 C>T), RS1000039623 (11:100899160 G>A), RS1000039914 (11:100844843 G>A), RS1000048871 (11:100913021 A>G), RS1000054019 (11:100838140 A>G), RS1000085106 (11:100930969 C>T), RS1000092529 (11:100802838 T>A,C), RS1000113188 (11:100989090 G>A), RS1000121712 (11:100705420 T>G), RS1000143643 (11:100808649 C>T), RS1000147893 (11:100865827 A>G), RS1000155970 (11:100905134 C>G,T), RS1000161606 (11:100725553 G>C)

Disease associations

OMIM: gene MIM:615936 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
interstitial lung disease	Limited	Autosomal recessive

Mondo (1): interstitial lung disease (MONDO:0015925)

Orphanet (0):

HPO phenotypes

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

GWAS associations

85 associations (top):

Study	Trait	p-value
GCST001227_16	Systolic blood pressure	1.000000e-17
GCST001228_5	Diastolic blood pressure	2.000000e-15
GCST001236_25	Blood pressure	7.000000e-10
GCST001238_11	Hypertension	5.000000e-11
GCST002013_5	Menarche (age at onset)	3.000000e-06
GCST003272_11	Systolic blood pressure	8.000000e-07
GCST003273_15	Diastolic blood pressure	2.000000e-06
GCST003275_8	Mean arterial pressure	2.000000e-12
GCST004280_38	Diastolic blood pressure	7.000000e-08
GCST004611_183	High light scatter reticulocyte count	1.000000e-15
GCST004612_146	High light scatter reticulocyte percentage of red cells	2.000000e-14
GCST004619_160	Reticulocyte fraction of red cells	7.000000e-14
GCST004622_113	Reticulocyte count	2.000000e-15
GCST004776_61	Systolic blood pressure	8.000000e-11
GCST004777_27	Diastolic blood pressure	2.000000e-08
GCST005194_121	Coronary artery disease	3.000000e-09
GCST005195_93	Coronary artery disease	7.000000e-11
GCST005196_53	Coronary artery disease	3.000000e-09
GCST005212_8	Asthma	2.000000e-06
GCST005978_13	Diastolic blood pressure	1.000000e-09
GCST005979_18	Systolic blood pressure	8.000000e-12
GCST006010_27	Mean arterial pressure	5.000000e-12
GCST006166_28	Diastolic blood pressure x alcohol consumption interaction (2df test)	3.000000e-28
GCST006166_96	Diastolic blood pressure x alcohol consumption interaction (2df test)	3.000000e-31
GCST006167_28	Mean arterial pressure x alcohol consumption interaction (2df test)	9.000000e-15
GCST006167_59	Mean arterial pressure x alcohol consumption interaction (2df test)	3.000000e-10
GCST006169_37	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	4.000000e-11
GCST006172_23	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-12
GCST006187_35	Diastolic blood pressure (cigarette smoking interaction)	1.000000e-40
GCST006188_40	Systolic blood pressure (cigarette smoking interaction)	2.000000e-39

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0004703	age at menarche
EFO:0007986	reticulocyte count
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0007796	parental longevity
EFO:0005763	pulse pressure measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004327	electrocardiography
EFO:0009473	hemolysis
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017563	Lung Diseases, Interstitial	C08.381.483

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	4
Aflatoxin B1	affects expression, increases expression, increases methylation	3
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
entinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
hydroquinone	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00637065	PHASE4	UNKNOWN	Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
NCT00882817	PHASE4	COMPLETED	Pulmonary Rehabilitation in Interstitial Lung Diseases
NCT02143687	PHASE4	COMPLETED	Patients With Pulmonary Hypertension or Interstitial Lung Disease at Altitude - Effect of Oxygen on Exercise Performance
NCT02150616	PHASE4	UNKNOWN	Patients With Pulmonary Hypertension or Interstitial Lung Disease at Altitude - Effect of Oxygen on Breathing and Sleep
NCT02622022	PHASE4	COMPLETED	Palliation of Dyspnea With Morphine in Patients With Interstitial Lung Disease
NCT02821689	PHASE4	UNKNOWN	Pirfenidone in Progressive Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis
NCT04036721	PHASE4	SUSPENDED	Coorticosteroid Regimen in Patients With Anti-PD-1/PD-L1 Induced Pneumonitis
NCT04311567	PHASE4	TERMINATED	Effects of Tofacitinib vs Methotrexate on Rheumatoid Arthritis Interstitial Lung Disease
NCT04619680	PHASE4	COMPLETED	The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT04988282	PHASE4	COMPLETED	Systemic Corticosteroids in Treatment of Post-COVID-19 Interstitial Lung Disease
NCT05129410	PHASE4	UNKNOWN	Clinical Study of MMF in Treatment of IIM-ILD and Its Effect on Peripheral Blood Treg Cells
NCT05375435	PHASE4	UNKNOWN	Efficacy and Safety of Triple Therapy in Patients With Anti-MDA5 Antibody-positive Dermatomyositis
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT07077486	PHASE4	RECRUITING	Effects of Telitacicept vs Cyclophosphamide on Lupus Related Interstitial Lung Disease
NCT07319598	PHASE4	RECRUITING	A Study to Test Tetrandrine Tablets for Connective Tissue Disease-Related Lung Disease
NCT07570888	PHASE4	NOT_YET_RECRUITING	This is a Trial Designed to Evaluate the Combination of Nerandomilast With Mycophenolate Across a Wide Variety of Pulmonary Fibrosis Subtypes, With the Aim of Providing Clinicians With Assurance That This is an Appropriate Therapeutic Combination.
NCT01570764	PHASE3	COMPLETED	Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
NCT02896205	PHASE3	COMPLETED	Study to Compare the Efficacy of Mycophenolate Mofetil in Systemic Sclerosis Related Early Interstitial Lung Disease
NCT03018756	PHASE3	COMPLETED	Nebulized Fentanyl in Patients With Mild to Moderate Interstitial Lung Disease and Chronic Dyspnea
NCT03770663	PHASE3	UNKNOWN	Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease
NCT04708782	PHASE3	COMPLETED	Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT05255991	PHASE3	COMPLETED	Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT05943535	PHASE3	RECRUITING	Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
NCT06297096	PHASE3	RECRUITING	Study of the Efficacy of Nintedanib+Tocilizumab in Patients With Systemic Sclerosis and Interstitial Lung Disease
NCT06806592	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Helps People With Lungfibrosis Related to Rheumatic Diseases
NCT07179380	PHASE3	RECRUITING	Efficacy and Safety Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
NCT07201922	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Can Help Slow Down Changes in the Lung in People With a Family History of Pulmonary Fibrosis
NCT07234032	PHASE3	NOT_YET_RECRUITING	An Open-Label Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
NCT07540988	PHASE3	NOT_YET_RECRUITING	FIBRONEER-ACT: A Study to Test Whether Nerandomilast Helps People With Fibrosing Interstitial Lung Disease at Risk for Disease Progression
NCT07613099	PHASE3	NOT_YET_RECRUITING	Evaluation of Fibrotic Disease Activity in Cardiopulmonary Disorders Using 18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74 PET/CT Imaging)
NCT00678821	PHASE2	COMPLETED	Aerobic Exercise in Patients With Pulmonary Hypertension
NCT00705133	PHASE2	COMPLETED	Treprostinil Therapy For Patients With Interstitial Lung Disease And Severe Pulmonary Arterial Hypertension
NCT00883129	PHASE2	COMPLETED	Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II)
NCT01203943	PHASE2	TERMINATED	A Study to Characterize the Safety, PK and Biological Activity of CC-930 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01280994	PHASE2	RECRUITING	Hyperpolarized 129Xe MRI for Imaging Pulmonary Function
NCT01381666	PHASE2	TERMINATED	Evaluation of the Diagnostic Utility of INS316 in Patients With Interstitial Lung Diseases (01-701)
NCT01559129	PHASE2	TERMINATED	Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness for Patients With Systemic Sclerosis With Interstitial Lung Disease