ARHGEF35

Summary

ARHGEF35 (Rho guanine nucleotide exchange factor 35, HGNC:33846) is a protein-coding gene on chromosome 7q35, encoding Rho guanine nucleotide exchange factor 35 (A5YM69).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 93 total — 1 pathogenic
• MANE Select transcript: NM_001003702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33846
Approved symbol	ARHGEF35
Name	Rho guanine nucleotide exchange factor 35
Location	7q35
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43692, CTAGE4
Ensembl gene	ENSG00000213214
Ensembl biotype	protein_coding
Entrez	445328

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000378115, ENST00000688754, ENST00000852510, ENST00000912150, ENST00000912151, ENST00000912152, ENST00000912153

RefSeq mRNA: 2 — MANE Select: NM_001003702 NM_001003702, NM_001368318

CCDS: CCDS34770

Canonical transcript exons

ENST00000378115 — 2 exons

Exon	Start	End
ENSE00001405572	144195538	144195833
ENSE00001476332	144186083	144188395

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 86.51.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	86.51	gold quality
rectum	UBERON:0001052	85.37	gold quality
islet of Langerhans	UBERON:0000006	83.14	gold quality
duodenum	UBERON:0002114	83.02	gold quality
tonsil	UBERON:0002372	81.34	gold quality
zone of skin	UBERON:0000014	81.08	gold quality
skin of abdomen	UBERON:0001416	80.96	gold quality
skin of leg	UBERON:0001511	80.96	gold quality
thymus	UBERON:0002370	80.69	silver quality
esophagus mucosa	UBERON:0002469	80.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.51	gold quality
left lobe of thyroid gland	UBERON:0001120	80.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.48	gold quality
thyroid gland	UBERON:0002046	79.75	gold quality
right lobe of thyroid gland	UBERON:0001119	79.66	gold quality
colonic epithelium	UBERON:0000397	78.99	gold quality
adult mammalian kidney	UBERON:0000082	78.66	gold quality
endometrium	UBERON:0001295	78.61	gold quality
placenta	UBERON:0001987	77.80	gold quality
lower esophagus mucosa	UBERON:0035834	77.51	gold quality
minor salivary gland	UBERON:0001830	77.45	gold quality
kidney	UBERON:0002113	77.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.84	gold quality
pancreas	UBERON:0001264	76.71	gold quality
saliva-secreting gland	UBERON:0001044	76.61	gold quality
transverse colon	UBERON:0001157	74.98	gold quality
gall bladder	UBERON:0002110	74.78	gold quality
metanephros cortex	UBERON:0010533	73.81	gold quality
cortex of kidney	UBERON:0001225	73.76	gold quality
small intestine	UBERON:0002108	73.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting ARHGEF35, 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-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-548AR-3P	99.85	71.26	3889

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
caenorhabditis_elegans		WBGENE00019487

Paralogs (6): ARHGEF5 (ENSG00000050327), NGEF (ENSG00000066248), ARHGEF26 (ENSG00000114790), ARHGEF16 (ENSG00000130762), ARHGEF19 (ENSG00000142632), ARHGEF15 (ENSG00000198844)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 35 — A5YM69 (reviewed: A5YM69)

Alternative names: Rho guanine nucleotide exchange factor 5-like protein

All UniProt accessions (1): A5YM69

RefSeq proteins (2): NP_001003702, NP_001355247 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029212	ARHGEF5/35_N	Domain

Pfam: PF15441

UniProt features (9 total): compositionally biased region 5, chain 1, region of interest 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5YM69-F1	44.69	0.00

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 (1): 184

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: 53 (showing top): GCANCTGNY_MYOD_Q6, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOBP_VESICLE_MEDIATED_TRANSPORT, NFKB_Q6, NFKB_C, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, FREAC3_01, WTGAAAT_UNKNOWN, GOBP_SECRETION, HNF1_01, chr7q35, TGGAAA_NFAT_Q4_01, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOBP_GOLGI_VESICLE_TRANSPORT

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

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

Protein interactions and networks

STRING

446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF35	CD8B2	A6NJW9	607
ARHGEF35	ARHGEF37	A1IGU5	513
ARHGEF35	PTPN20	Q4JDL3	492
ARHGEF35	FAM72C	H0Y354	452
ARHGEF35	FAM72B	Q86X60	451
ARHGEF35	DUSP22	Q9NRW4	443
ARHGEF35	ARHGEF6	Q15052	433
ARHGEF35	TCAF1	Q9Y4C2	433
ARHGEF35	E9PD41	E9PD41	425
ARHGEF35	MYADML2	A6NDP7	422
ARHGEF35	ZSCAN30	Q86W11	419
ARHGEF35	EOLA1	Q8TE69	418
ARHGEF35	FAM72D	Q6L9T8	410
ARHGEF35	ARHGAP42	A6NI28	409
ARHGEF35	ARHGEF33	A8MVX0	407

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
ARHGEF35	OBSL1	psi-mi:“MI:0914”(association)	0.530
NPHP3	ARHGEF35	psi-mi:“MI:0914”(association)	0.350
ARHGEF35	OBSL1	psi-mi:“MI:0914”(association)	0.350
ARHGEF35	RFPL4A	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): ARHGEF5 (Affinity Capture-MS), ALAD (Affinity Capture-MS), ARHGEF35 (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), TYMS (Affinity Capture-MS), ARHGEF35 (Synthetic Lethality), ARHGEF35 (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), ARHGEF5 (Affinity Capture-MS), ALAD (Affinity Capture-MS), ARHGEF35 (Affinity Capture-MS), ARHGEF35 (Affinity Capture-MS), ARHGEF35 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GUA9, A0JNH1, A2TJV2, A5PJD3, A5YM69, A6QP92, A7YY35, A8MUA0, D3Z1D3, E9Q3S4, E9Q7D5, M0RD54, O02665, O94854, O95359, P43359, P58871, Q0VDD7, Q0VF49, Q12774, Q3KR64, Q4R736, Q5PSV9, Q5QJ38, Q5R5G4, Q5RJL0, Q5SWP3, Q5ZK13, Q69ZZ9, Q6AXX2, Q6AYA8, Q6DIA7, Q6NXZ1, Q6ZRC1, Q711Q0, Q80VY2, Q86TB3, Q8BHB7, Q8BI84, Q8VBT6

Diamond homologs: A5YM69, E9Q7D5, Q12774, O94989, Q3U5C8, Q5BKC9, Q5FWH6, Q5RDX5, Q5VV41, Q8BWA8, Q8C120, Q8CHT1, Q8IW93, Q8N5V2, Q96DR7, Q8TEJ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	73
Likely benign	16
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57046	GRCh38/hg38 7q34-35(chr7:142578948-144254897)x1	Pathogenic

SpliceAI

228 predictions. Top by Δscore:

Variant	Effect	Δscore
7:144195534:CCAC:C	donor_loss	1.0000
7:144195535:CA:C	donor_loss	1.0000
7:144195536:A:AT	donor_loss	1.0000
7:144188393:ATCC:A	acceptor_loss	0.9900
7:144188394:TCCT:T	acceptor_loss	0.9900
7:144188397:T:C	acceptor_loss	0.9900
7:144195536:A:AC	donor_gain	0.9900
7:144195537:C:CC	donor_gain	0.9900
7:144188396:C:CC	acceptor_gain	0.9800
7:144188394:TC:T	acceptor_gain	0.9700
7:144188395:CC:C	acceptor_gain	0.9700
7:144195534:CCACC:C	donor_gain	0.9600
7:144188396:CTAAG:C	acceptor_gain	0.9500
7:144188393:ATCCT:A	acceptor_gain	0.9400
7:144195537:CCTGG:C	donor_gain	0.9000
7:144187734:T:A	donor_gain	0.8500
7:144195462:T:TA	donor_gain	0.8500
7:144188395:CCTAA:C	acceptor_gain	0.8400
7:144188409:A:T	acceptor_loss	0.8300
7:144188393:ATC:A	acceptor_gain	0.8200
7:144188397:T:G	acceptor_gain	0.8000
7:144195458:T:TA	donor_gain	0.7700
7:144195452:T:TA	donor_gain	0.7600
7:144188391:GAATC:G	acceptor_gain	0.7500
7:144194720:TTGGA:T	donor_gain	0.7400
7:144195537:CCTG:C	donor_gain	0.7400
7:144195529:GGCAC:G	donor_gain	0.7300
7:144195536:AC:A	donor_gain	0.7300
7:144195537:CC:C	donor_gain	0.7300
7:144188392:AATC:A	acceptor_gain	0.7200

AlphaMissense

3176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:144187928:A:C	F152L	0.898
7:144187928:A:T	F152L	0.898
7:144187930:A:G	F152L	0.898
7:144188150:A:C	F78L	0.894
7:144188150:A:T	F78L	0.894
7:144188152:A:G	F78L	0.894
7:144188324:G:C	F20L	0.892
7:144188324:G:T	F20L	0.892
7:144188326:A:G	F20L	0.892
7:144188234:C:A	W50C	0.869
7:144188234:C:G	W50C	0.869
7:144188236:A:G	W50R	0.842
7:144188236:A:T	W50R	0.842
7:144187664:A:C	F240L	0.784
7:144187664:A:T	F240L	0.784
7:144187666:A:G	F240L	0.784
7:144188294:G:C	S30R	0.771
7:144188294:G:T	S30R	0.771
7:144188296:T:G	S30R	0.771
7:144187118:A:C	F422L	0.743
7:144187118:A:T	F422L	0.743
7:144187120:A:G	F422L	0.743
7:144186977:A:C	F469L	0.710
7:144186977:A:T	F469L	0.710
7:144186979:A:G	F469L	0.710
7:144188300:C:A	M28I	0.667
7:144188300:C:G	M28I	0.667
7:144188300:C:T	M28I	0.667
7:144187238:C:A	W382C	0.654
7:144187238:C:G	W382C	0.654

dbSNP variants (sampled 300 via entrez): RS1000492238 (7:144186998 G>A), RS1001929716 (7:144190407 G>A), RS1001982186 (7:144192085 G>C), RS1004049686 (7:144192425 A>G), RS1004342940 (7:144197104 C>G), RS1008813823 (7:144186680 G>A), RS1012901182 (7:144189846 A>C), RS1013249306 (7:144189889 C>T), RS1013782627 (7:144187680 T>C), RS1015806798 (7:144192445 G>A), RS1019746101 (7:144186720 A>G,T), RS1023363214 (7:144191358 A>C,T), RS1024718620 (7:144187690 C>T), RS1025023083 (7:144189989 A>G), RS1025721639 (7:144186625 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010136_23	Fruit consumption	5.000000e-08
GCST010136_24	Fruit consumption	1.000000e-48

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	decreases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
Zoledronic Acid	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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