ARHGEF37

Summary

ARHGEF37 (Rho guanine nucleotide exchange factor 37, HGNC:34430) is a protein-coding gene on chromosome 5q32, encoding Rho guanine nucleotide exchange factor 37 (A1IGU5). Probable guanine nucleotide exchange factor (GEF) involved in clathrin-mediated endocytosis, probably playing a role in the late stages of the process.

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be active in cytoplasm.

Source: NCBI Gene 389337 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 126 total
• MANE Select transcript: NM_001001669

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34430
Approved symbol	ARHGEF37
Name	Rho guanine nucleotide exchange factor 37
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ41603
Ensembl gene	ENSG00000183111
Ensembl biotype	protein_coding
OMIM	620664
Entrez	389337

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000333677, ENST00000505810, ENST00000509831, ENST00000857359, ENST00000857360, ENST00000857361, ENST00000857362, ENST00000857363, ENST00000941572, ENST00000941573, ENST00000941574, ENST00000941575

RefSeq mRNA: 1 — MANE Select: NM_001001669 NM_001001669

CCDS: CCDS43385

Canonical transcript exons

ENST00000333677 — 13 exons

Exon	Start	End
ENSE00001310399	149624012	149624140
ENSE00001328499	149627076	149627271
ENSE00001373846	149631982	149634968
ENSE00001507544	149621733	149622062
ENSE00001507545	149620354	149620464
ENSE00001507546	149618938	149619042
ENSE00001507547	149618176	149618306
ENSE00001507549	149616567	149616766
ENSE00001533141	149609548	149609695
ENSE00001533143	149597759	149597955
ENSE00001533144	149581498	149581624
ENSE00003678214	149628809	149628966
ENSE00003785630	149601108	149601231

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.05.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8660 / max 231.7333, expressed in 646 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59380	2.3589	551
59379	0.4739	251
59386	0.0112	8
59383	0.0106	5
59384	0.0086	6
59385	0.0028	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.05	gold quality
upper arm skin	UBERON:0004263	97.95	gold quality
seminal vesicle	UBERON:0000998	97.50	gold quality
pancreatic ductal cell	CL:0002079	96.70	gold quality
amniotic fluid	UBERON:0000173	96.02	gold quality
inferior vagus X ganglion	UBERON:0005363	95.99	gold quality
trigeminal ganglion	UBERON:0001675	94.81	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.58	gold quality
subthalamic nucleus	UBERON:0001906	94.47	gold quality
spinal cord	UBERON:0002240	94.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.36	gold quality
medial globus pallidus	UBERON:0002477	94.16	gold quality
medulla oblongata	UBERON:0001896	93.92	gold quality
globus pallidus	UBERON:0001875	93.77	gold quality
dorsal root ganglion	UBERON:0000044	93.55	gold quality
upper leg skin	UBERON:0004262	93.50	gold quality
gingival epithelium	UBERON:0001949	93.37	gold quality
sperm	CL:0000019	93.24	gold quality
nasal cavity epithelium	UBERON:0005384	92.92	gold quality
palpebral conjunctiva	UBERON:0001812	92.54	gold quality
substantia nigra pars compacta	UBERON:0001965	92.33	gold quality
superior vestibular nucleus	UBERON:0007227	92.28	gold quality
cardia of stomach	UBERON:0001162	92.17	gold quality
penis	UBERON:0000989	91.99	gold quality
tibial nerve	UBERON:0001323	91.89	gold quality
epithelial cell of pancreas	CL:0000083	91.88	gold quality
pigmented layer of retina	UBERON:0001782	91.72	gold quality
midbrain	UBERON:0001891	91.53	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.48	gold quality
substantia nigra	UBERON:0002038	91.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting ARHGEF37, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3156-3P	99.76	66.72	939
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-3059-5P	99.70	69.93	2491
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-182-3P	99.57	67.57	825

Literature-anchored findings (GeneRIF, showing 1)

• ArhGEF37 was identified as a constituent of clathrin-mediated endocytosis: ArhGEF37 accumulated at dynamin 2-rich late endocytic sites. Endocytosis rates increased in the presence of ArhGEF37. (PMID:30926623)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgef37	ENSDARG00000002463
mus_musculus	Arhgef37	ENSMUSG00000045094
rattus_norvegicus	Arhgef37	ENSRNOG00000025502
caenorhabditis_elegans		WBGENE00044989

Paralogs (2): DNMBP (ENSG00000107554), ARHGEF38 (ENSG00000236699)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 37 — A1IGU5 (reviewed: A1IGU5)

All UniProt accessions (2): A1IGU5, D6RJH4

UniProt curated annotations — full annotation on UniProt →

Function. Probable guanine nucleotide exchange factor (GEF) involved in clathrin-mediated endocytosis, probably playing a role in the late stages of the process.

RefSeq proteins (1): NP_001001669* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001452	SH3_domain	Domain
IPR004148	BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR035636	ARHGEF37_SH3_2	Domain
IPR035823	ARHGEF37_SH3_C1	Domain
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051492	Dynamin-Rho_GEF	Family

Pfam: PF00018, PF00621, PF07653

UniProt features (11 total): sequence variant 5, domain 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1IGU5-F1	83.73	0.52

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
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

MSigDB gene sets: 111 (showing top): REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GTGCCTT_MIR506, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GATA1_04, MEF2_Q6_01, P53_DECAMER_Q2, GTGTGAG_MIR342, chr5q32, LEIN_CEREBELLUM_MARKERS, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (0):

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signal Transduction	2
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Death Receptor Signaling	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF37	FCHSD1	Q86WN1	516
ARHGEF37	ARHGEF35	A5YM69	513
ARHGEF37	ARHGAP44	Q17R89	492
ARHGEF37	ARHGEF39	Q8N4T4	468
ARHGEF37	MTSS2	Q765P7	461
ARHGEF37	ARHGAP42	A6NI28	456
ARHGEF37	ARHGAP4	P98171	446
ARHGEF37	TCEA2	Q15560	421
ARHGEF37	EPB41L4A	Q9HCS5	399
ARHGEF37	PACSIN3	Q9UKS6	397
ARHGEF37	ARHGEF40	Q8TER5	396
ARHGEF37	TLCD3B	Q71RH2	395
ARHGEF37	ARHGAP45	Q92619	392
ARHGEF37	FCHSD2	O94868	391
ARHGEF37	BAIAP2L1	Q9UHR4	390

IntAct

6 interactions, top by confidence:

A	B	Type	Score
BIN3	ARHGEF37	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
PRPS2	ARHGEF37	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): ARHGEF37 (Affinity Capture-MS), ARHGEF37 (Affinity Capture-RNA), ARHGEF37 (Affinity Capture-RNA), ARHGEF37 (Affinity Capture-MS), ARHGEF37 (Affinity Capture-MS), ARHGEF37 (Two-hybrid), ARHGEF37 (Affinity Capture-MS)

ESM2 similar proteins: A1IGU3, A1IGU4, A1IGU5, A6QP29, B1AVH7, B2RUP2, B5DFA1, D2H0G5, D3ZFJ3, O15068, O55043, P00530, P07332, P14238, P16879, P55194, P98171, Q0GNC1, Q14155, Q15052, Q27J81, Q3U5C8, Q3UMR0, Q58EX7, Q5VV41, Q5XXR3, Q5ZLR6, Q60I26, Q63406, Q64096, Q6PFY1, Q6PGG2, Q70J99, Q7TNH6, Q80TT2, Q80VK6, Q86WN1, Q8C2K1, Q8C6B2, Q8CJ00

Diamond homologs: A1IGU3, A1IGU4, A1IGU5, A1ZAY1, E7F1U2, O15068, O15085, O77775, P10569, P15498, P19878, P35991, Q08DN7, Q3LAC4, Q5DU57, Q60992, Q63406, Q69ZK0, Q70Z35, Q80VK6, Q8TCU6, Q96N96, Q9NHV9, Q9NXL2, O60229, P40995, Q1LUA6, Q5BKC9, Q5RDX5, Q64096, Q6RFZ7, Q8CHT1, Q8N5V2, Q9ES67, P52735, Q55E26, Q6TXD4, A4RF61, A5D7F8, A7E3N7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2167 predictions. Top by Δscore:

Variant	Effect	Δscore
5:149581621:GCGG:G	donor_gain	1.0000
5:149581622:CGGG:C	donor_loss	1.0000
5:149581623:GG:G	donor_gain	1.0000
5:149581623:GGGT:G	donor_loss	1.0000
5:149581624:GG:G	donor_gain	1.0000
5:149581624:GGTG:G	donor_loss	1.0000
5:149581625:G:GG	donor_gain	1.0000
5:149581626:T:A	donor_loss	1.0000
5:149601103:TCCA:T	acceptor_loss	1.0000
5:149601106:A:AG	acceptor_gain	1.0000
5:149601107:G:GT	acceptor_gain	1.0000
5:149601107:GT:G	acceptor_gain	1.0000
5:149601107:GTT:G	acceptor_gain	1.0000
5:149601107:GTTGC:G	acceptor_gain	1.0000
5:149601207:G:GT	donor_gain	1.0000
5:149601224:GCTA:G	donor_gain	1.0000
5:149601228:GTTG:G	donor_gain	1.0000
5:149601231:GGT:G	donor_loss	1.0000
5:149601232:G:GG	donor_gain	1.0000
5:149601232:GT:G	donor_loss	1.0000
5:149601233:T:A	donor_loss	1.0000
5:149609691:GTGGT:G	donor_gain	1.0000
5:149609696:G:GG	donor_gain	1.0000
5:149616721:G:GT	donor_gain	1.0000
5:149616740:A:AG	donor_gain	1.0000
5:149616759:GGAA:G	donor_gain	1.0000
5:149616760:G:GT	donor_gain	1.0000
5:149616763:G:GG	donor_gain	1.0000
5:149616763:GTGG:G	donor_loss	1.0000
5:149616765:GG:G	donor_gain	1.0000

AlphaMissense

4381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:149632090:T:A	W643R	0.990
5:149632090:T:C	W643R	0.990
5:149632127:T:A	V655E	0.990
5:149632092:G:C	W643C	0.989
5:149632092:G:T	W643C	0.989
5:149632000:T:C	F613L	0.988
5:149632002:T:A	F613L	0.988
5:149632002:T:G	F613L	0.988
5:149631989:C:A	A609D	0.985
5:149632049:T:A	V629E	0.983
5:149632138:T:C	F659L	0.982
5:149632140:C:A	F659L	0.982
5:149632140:C:G	F659L	0.982
5:149627209:T:A	V533E	0.981
5:149627260:T:A	V550E	0.980
5:149632031:T:C	L623P	0.979
5:149627253:T:A	W548R	0.978
5:149627253:T:C	W548R	0.978
5:149632069:G:C	D636H	0.978
5:149616621:G:C	R171S	0.977
5:149616621:G:T	R171S	0.977
5:149621944:T:C	L406P	0.977
5:149632100:T:A	V646E	0.977
5:149632142:T:C	L660S	0.977
5:149632070:A:T	D636V	0.976
5:149632091:G:C	W643S	0.976
5:149632121:G:A	G653D	0.976
5:149632123:T:G	Y654D	0.976
5:149618953:T:C	F269L	0.975
5:149618955:T:A	F269L	0.975

dbSNP variants (sampled 300 via entrez): RS1000082139 (5:149584502 T>C), RS1000107762 (5:149608034 C>G,T), RS1000143839 (5:149619154 C>T), RS1000175249 (5:149604631 C>G,T), RS1000182634 (5:149578491 T>C,G), RS1000193365 (5:149622610 G>C), RS1000282208 (5:149553469 T>G), RS1000283898 (5:149598141 C>A), RS1000294173 (5:149551720 T>C), RS1000336463 (5:149565555 C>A), RS1000367169 (5:149610546 C>A,T), RS1000419976 (5:149580268 C>T), RS1000434155 (5:149559523 A>G), RS1000473336 (5:149571848 A>C), RS1000487884 (5:149559292 G>A,C)

Disease associations

OMIM: gene MIM:620664 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001850_9	Major depressive disorder	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
belinostat	decreases expression, affects cotreatment	2
Calcitriol	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
2,4-dichlorophenol	increases methylation	1
methyleugenol	increases expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methapyrilene	decreases methylation	1
N-Nitrosopyrrolidine	increases expression	1
Testosterone	increases expression, affects cotreatment	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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