ARHGEF19

Summary

ARHGEF19 (Rho guanine nucleotide exchange factor 19, HGNC:26604) is a protein-coding gene on chromosome 1p36.13, encoding Rho guanine nucleotide exchange factor 19 (Q8IW93). Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPase.

Guanine nucleotide exchange factors (GEFs) such as ARHGEF19 accelerate the GTPase activity of Rho GTPases (see RHOA, MIM 165390).

Source: NCBI Gene 128272 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 148 total — 1 pathogenic
• MANE Select transcript: NM_153213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26604
Approved symbol	ARHGEF19
Name	Rho guanine nucleotide exchange factor 19
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33962, WGEF
Ensembl gene	ENSG00000142632
Ensembl biotype	protein_coding
OMIM	612496
Entrez	128272

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000270747, ENST00000441785, ENST00000449495, ENST00000471928, ENST00000478117, ENST00000478210, ENST00000898690, ENST00000928712, ENST00000928713, ENST00000928714, ENST00000928715, ENST00000947389

RefSeq mRNA: 1 — MANE Select: NM_153213 NM_153213

CCDS: CCDS170

Canonical transcript exons

ENST00000270747 — 16 exons

Exon	Start	End
ENSE00000955436	16206948	16207210
ENSE00001031683	16207944	16208225
ENSE00001031688	16207675	16207777
ENSE00001031690	16207522	16207598
ENSE00001164285	16202416	16202574
ENSE00001164330	16208643	16209083
ENSE00001274966	16197854	16198744
ENSE00001341474	16212502	16212652
ENSE00003458701	16206180	16206340
ENSE00003502999	16205931	16206083
ENSE00003587242	16199150	16199254
ENSE00003588176	16205351	16205425
ENSE00003607928	16201782	16201861
ENSE00003643945	16204759	16204919
ENSE00003643957	16205087	16205176
ENSE00003660699	16205538	16205667

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 91.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2892 / max 52.6834, expressed in 1011 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10528	1.8571	338
10524	0.8947	530
10525	0.5373	296

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	91.61	gold quality
upper arm skin	UBERON:0004263	90.91	silver quality
lower esophagus mucosa	UBERON:0035834	90.49	gold quality
skin of leg	UBERON:0001511	89.65	gold quality
right adrenal gland	UBERON:0001233	88.80	gold quality
right adrenal gland cortex	UBERON:0035827	88.56	gold quality
zone of skin	UBERON:0000014	88.19	gold quality
right lobe of thyroid gland	UBERON:0001119	87.78	gold quality
left adrenal gland cortex	UBERON:0035825	87.43	gold quality
esophagus mucosa	UBERON:0002469	87.42	gold quality
left adrenal gland	UBERON:0001234	87.37	gold quality
adrenal cortex	UBERON:0001235	86.55	gold quality
left lobe of thyroid gland	UBERON:0001120	85.89	gold quality
right ovary	UBERON:0002118	85.66	gold quality
minor salivary gland	UBERON:0001830	85.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.58	gold quality
stromal cell of endometrium	CL:0002255	85.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.34	gold quality
ectocervix	UBERON:0012249	85.33	gold quality
left ovary	UBERON:0002119	85.14	gold quality
saliva-secreting gland	UBERON:0001044	84.89	gold quality
thyroid gland	UBERON:0002046	84.84	gold quality
adrenal gland	UBERON:0002369	84.36	gold quality
endocervix	UBERON:0000458	84.21	gold quality
mouth mucosa	UBERON:0003729	84.14	gold quality
vagina	UBERON:0000996	83.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.28	gold quality
body of uterus	UBERON:0009853	82.92	gold quality
left uterine tube	UBERON:0001303	82.74	gold quality
esophagus	UBERON:0001043	82.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting ARHGEF19, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-379-5P	97.52	67.81	485
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-6858-5P	96.05	64.59	1020

Literature-anchored findings (GeneRIF, showing 4)

• overcomes the suppressive influence of miR-503 in hepatocellular carcinoma cells (PMID:24405610)
• These findings suggest that ARHGEF19 upregulation, due to the low expression of miR-29 in non-small cell lung cancer tissues, may play a crucial role in non-small cell lung cancer tumorigenesis by activating MAPK signaling (PMID:29164615)
• ARHGEF19 regulates MAPK/ERK signaling and promotes the progression of small cell lung cancer. (PMID:32993957)
• Dishevelled2 activates WGEF via its interaction with a unique internal peptide motif of the GEF. (PMID:38714795)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgef19	ENSDARG00000078853
mus_musculus	Arhgef19	ENSMUSG00000028919
rattus_norvegicus	Arhgef19	ENSRNOG00000047967
caenorhabditis_elegans		WBGENE00019487

Paralogs (6): ARHGEF5 (ENSG00000050327), NGEF (ENSG00000066248), ARHGEF26 (ENSG00000114790), ARHGEF16 (ENSG00000130762), ARHGEF15 (ENSG00000198844), ARHGEF35 (ENSG00000213214)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 19 — Q8IW93 (reviewed: Q8IW93)

Alternative names: Ephexin-2

All UniProt accessions (3): Q8IW93, H0Y4D8, Q5TEV0

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPase.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IW93-1	1	yes
Q8IW93-2	2

RefSeq proteins (1): NP_694945* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR047270	PH_ephexin	Domain
IPR047271	Ephexin-like	Family

Pfam: PF00621, PF07653

UniProt features (15 total): region of interest 5, domain 3, compositionally biased region 3, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8YR7	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IW93-F1	65.80	0.38

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 82 (showing top): GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, SP1_Q2_01, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_WOUND_HEALING, SOX9_B1, TGCTGAY_UNKNOWN, TGGNNNNNNKCCAR_UNKNOWN, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, E2F1_Q3_01, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY

GO Biological Process (4): regulation of actin cytoskeleton organization (GO:0032956), wound healing (GO:0042060), regulation of small GTPase mediated signal transduction (GO:0051056), Wnt signaling pathway, planar cell polarity pathway (GO:0060071)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
RHO GTPase cycle	3
Signal Transduction	3
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase regulator activity	2
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
response to wounding	1
tissue regeneration	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
non-canonical Wnt signaling pathway	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF19	DAAM1	Q9Y4D1	827
ARHGEF19	RHOA	P06749	564
ARHGEF19	ALS2CL	Q60I27	559
ARHGEF19	BLTP1	Q2LD37	542
ARHGEF19	ARHGEF38	Q9NXL2	540
ARHGEF19	PLEKHG4B	Q96PX9	520
ARHGEF19	DVL1	O14640	519
ARHGEF19	CDC42	P21181	512
ARHGEF19	LACRT	Q9GZZ8	493
ARHGEF19	ARHGEF9	O43307	491
ARHGEF19	ZMIZ2	Q8NF64	471
ARHGEF19	ARHGEF10L	Q9HCE6	450
ARHGEF19	RASGRF2	O14827	446
ARHGEF19	ARHGEF33	A8MVX0	444
ARHGEF19	CDC42SE1	Q9NRR8	437

IntAct

14 interactions, top by confidence:

A	B	Type	Score
YWHAE	RGS12	psi-mi:“MI:0914”(association)	0.610
ARHGEF19	PAK5	psi-mi:“MI:0915”(physical association)	0.560
YWHAE	SRSF10	psi-mi:“MI:0914”(association)	0.560
ADAM10	ARHGEF19	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF19	RAC1	psi-mi:“MI:0915”(physical association)	0.400
ARHGEF19	RHOA	psi-mi:“MI:0915”(physical association)	0.400
ARHGEF19	DVL1	psi-mi:“MI:0915”(physical association)	0.400
DAAM1	ARHGEF19	psi-mi:“MI:0915”(physical association)	0.400
SRGAP1	SRGAP2	psi-mi:“MI:0914”(association)	0.350
Arhgap1	ZNF207	psi-mi:“MI:0914”(association)	0.350
ARHGEF19	PAK5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (55): ARHGEF19 (Two-hybrid), ARHGEF19 (Affinity Capture-MS), ARHGEF19 (FRET), ARHGEF19 (Affinity Capture-MS), ARID3B (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), C5orf24 (Affinity Capture-MS), C9orf78 (Affinity Capture-MS), CCDC12 (Affinity Capture-MS), CCDC137 (Affinity Capture-MS), CCDC86 (Affinity Capture-MS), CDCA5 (Affinity Capture-MS), CWC15 (Affinity Capture-MS), DGCR14 (Affinity Capture-MS), EBNA1BP2 (Affinity Capture-MS)

ESM2 similar proteins: A1IGU3, A1IGU4, A1IGU5, A6QP29, A7E3N7, B1AVH7, B2RUP2, B5DFA1, D2H0G5, D3ZFJ3, O15068, O55043, O94812, P00530, P07332, P14238, P16879, P55194, P97680, P98171, Q27J81, Q3U5C8, Q58EX7, Q5VV41, Q60I26, Q60I27, Q63406, Q64096, Q6PFY1, Q6PGG2, Q70J99, Q80TT2, Q80UW5, Q80VK6, Q86WN1, Q8C2K1, Q8C6B2, Q8CJ00, Q8IW93, Q8R5I4

Diamond homologs: A5YM69, E9Q7D5, O94989, Q12774, Q3U5C8, Q5BKC9, Q5FWH6, Q5RDX5, Q5VV41, Q8BWA8, Q8C120, Q8CHT1, Q8IW93, Q8N5V2, Q96DR7, Q8TEJ3, O42287, Q15811, Q9Z0R6, A1IGU3, A1IGU4, A1IGU5, Q62417, Q9NZM3, O60229, Q498M5, Q8BZT2, Q8IVI9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ARHGEF19	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 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
RHO GTPases Activate Formins	5	35.3×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	118
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2425113	NC_000001.10:g.(?16451710)(16532835_?)del	Pathogenic

SpliceAI

2686 predictions. Top by Δscore:

Variant	Effect	Δscore
1:16202414:A:AC	donor_gain	1.0000
1:16202414:ACT:A	donor_gain	1.0000
1:16202415:C:CA	donor_gain	1.0000
1:16202415:CT:C	donor_gain	1.0000
1:16202415:CTC:C	donor_gain	1.0000
1:16202572:AGCCT:A	acceptor_gain	1.0000
1:16202573:GC:G	acceptor_gain	1.0000
1:16202573:GCCTG:G	acceptor_gain	1.0000
1:16202574:CC:C	acceptor_gain	1.0000
1:16204751:CGACT:C	donor_loss	1.0000
1:16204753:ACT:A	donor_loss	1.0000
1:16204754:CTC:C	donor_loss	1.0000
1:16204755:TCAC:T	donor_loss	1.0000
1:16204757:A:AC	donor_gain	1.0000
1:16204757:ACT:A	donor_gain	1.0000
1:16204757:ACTC:A	donor_gain	1.0000
1:16204758:C:CA	donor_gain	1.0000
1:16204758:CT:C	donor_gain	1.0000
1:16204758:CTC:C	donor_gain	1.0000
1:16204758:CTCC:C	donor_gain	1.0000
1:16204758:CTCCT:C	donor_gain	1.0000
1:16204759:T:TA	donor_gain	1.0000
1:16204760:C:CA	donor_gain	1.0000
1:16204763:T:TA	donor_gain	1.0000
1:16204810:G:GA	donor_gain	1.0000
1:16204915:AAAAT:A	acceptor_gain	1.0000
1:16204916:AAAT:A	acceptor_gain	1.0000
1:16204917:AAT:A	acceptor_gain	1.0000
1:16204920:C:CC	acceptor_gain	1.0000
1:16205345:GCTCA:G	donor_loss	1.0000

AlphaMissense

5152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:16205565:C:A	R518S	1.000
1:16205565:C:G	R518S	1.000
1:16205566:C:A	R518M	1.000
1:16205566:C:G	R518T	1.000
1:16205575:G:C	P515R	1.000
1:16205575:G:T	P515H	1.000
1:16205578:A:G	L514P	1.000
1:16205584:A:G	L512P	1.000
1:16205586:G:C	F511L	1.000
1:16205586:G:T	F511L	1.000
1:16205587:A:G	F511S	1.000
1:16205588:A:G	F511L	1.000
1:16205602:A:G	L506P	1.000
1:16205973:A:T	V470D	1.000
1:16206069:A:G	L438P	1.000
1:16206078:A:G	L435P	1.000
1:16206081:A:G	F434S	1.000
1:16206185:G:C	S431R	1.000
1:16206185:G:T	S431R	1.000
1:16206187:T:G	S431R	1.000
1:16206273:A:G	F402S	1.000
1:16206294:A:G	L395P	1.000
1:16206296:G:C	S394R	1.000
1:16206296:G:T	S394R	1.000
1:16206298:T:G	S394R	1.000
1:16206318:G:A	S387F	1.000
1:16206318:G:T	S387Y	1.000
1:16206319:A:G	S387P	1.000
1:16206327:A:G	L384P	1.000
1:16206332:A:C	F382L	1.000

dbSNP variants (sampled 300 via entrez): RS1000318516 (1:16197731 C>T), RS1000517280 (1:16210494 A>T), RS1000763281 (1:16204212 A>G), RS1000780016 (1:16197487 T>C), RS1000982603 (1:16204018 T>C,G), RS1001036631 (1:16209938 G>A), RS1001233023 (1:16198026 G>C), RS1001906993 (1:16210654 G>A), RS1001946743 (1:16204314 C>G,T), RS1002074512 (1:16197769 G>A,C), RS1002107504 (1:16198071 G>C,T), RS1002150511 (1:16207217 G>A), RS1002379331 (1:16204598 C>A), RS1002463132 (1:16210324 C>T), RS1002815430 (1:16214389 C>T)

Disease associations

OMIM: gene MIM:612496 | disease phenotypes: MIM:116600

GenCC curated gene-disease

Mondo (1): cataract 6 multiple types (MONDO:0007288)

Orphanet (1): Early onset non-syndromic cataract (Orphanet:91492)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST005023_15	Initial pursuit acceleration	6.000000e-06
GCST006019_43	Gamma glutamyl transferase levels	1.000000e-36
GCST009464_29	Facial morphology	1.000000e-08
GCST010243_106	Apolipoprotein B levels	1.000000e-12
GCST010245_70	LDL cholesterol levels	9.000000e-10
GCST011349_33	Gamma glutamyl transferase levels	7.000000e-44
GCST011352_15	Alanine aminotransferase levels	5.000000e-09
GCST90011898_30	Alanine aminotransferase levels	1.000000e-54
GCST90011899_178	Aspartate aminotransferase levels	1.000000e-39
GCST90013405_66	Liver enzyme levels (alanine transaminase)	5.000000e-72
GCST90013407_4	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-300

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008434	initial pursuit acceleration
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	3
sodium arsenite	increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Carbamazepine	affects expression	1
Estradiol	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases expression	1
Medroxyprogesterone Acetate	increases expression	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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