ARHGAP27

Summary

ARHGAP27 (Rho GTPase activating protein 27, HGNC:31813) is a protein-coding gene on chromosome 17q21.31, encoding Rho GTPase-activating protein 27 (Q6ZUM4). Rho GTPase-activating protein which may be involved in clathrin-mediated endocytosis.

This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may pay a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 201176 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 148 total — 1 pathogenic
• MANE Select transcript: NM_001282290

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31813
Approved symbol	ARHGAP27
Name	Rho GTPase activating protein 27
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	CAMGAP1, FLJ43547, SH3P20
Ensembl gene	ENSG00000159314
Ensembl biotype	protein_coding
OMIM	610591
Entrez	201176

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 20 protein_coding, 12 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000290470, ENST00000376922, ENST00000524404, ENST00000526484, ENST00000527678, ENST00000528273, ENST00000528384, ENST00000528677, ENST00000529357, ENST00000531735, ENST00000532038, ENST00000532667, ENST00000532891, ENST00000579357, ENST00000581638, ENST00000581991, ENST00000582826, ENST00000590026, ENST00000685559, ENST00000691061, ENST00000703659, ENST00000703660, ENST00000703661, ENST00000703662, ENST00000868963, ENST00000868964, ENST00000868965, ENST00000868966, ENST00000868967, ENST00000917071, ENST00000917072, ENST00000962084, ENST00000962085, ENST00000962086, ENST00000962087

RefSeq mRNA: 19 — MANE Select: NM_001282290 NM_001282290, NM_001385384, NM_001385385, NM_001385386, NM_001385387, NM_001385388, NM_001385389, NM_001385390, NM_001385391, NM_001385392, NM_001385393, NM_001385394, NM_001385395, NM_001385396, NM_001385397, NM_001385398, NM_001385399, NM_174919, NM_199282

CCDS: CCDS11498, CCDS32670, CCDS74082, CCDS92340, CCDS92341, CCDS92342, CCDS92343

Canonical transcript exons

ENST00000610792 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2657 / max 279.7659, expressed in 1188 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166537	6.6956	501
166540	1.7565	434
166547	1.2439	530
166541	1.0259	452
166538	0.7355	202
166544	0.6205	376
166546	0.4164	229
166536	0.2782	129
166542	0.2009	112
166539	0.1926	121

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.12	gold quality
granulocyte	CL:0000094	98.67	gold quality
blood	UBERON:0000178	97.95	gold quality
monocyte	CL:0000576	97.38	gold quality
esophagus mucosa	UBERON:0002469	97.33	gold quality
leukocyte	CL:0000738	97.22	gold quality
mucosa of transverse colon	UBERON:0004991	96.86	gold quality
spleen	UBERON:0002106	96.71	gold quality
duodenum	UBERON:0002114	95.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.19	gold quality
vermiform appendix	UBERON:0001154	95.01	gold quality
minor salivary gland	UBERON:0001830	94.97	gold quality
small intestine	UBERON:0002108	94.74	gold quality
saliva-secreting gland	UBERON:0001044	94.44	gold quality
transverse colon	UBERON:0001157	94.16	gold quality
vagina	UBERON:0000996	93.62	gold quality
upper lobe of left lung	UBERON:0008952	93.54	gold quality
lymph node	UBERON:0000029	93.17	gold quality
apex of heart	UBERON:0002098	93.17	gold quality
skin of leg	UBERON:0001511	92.63	gold quality
zone of skin	UBERON:0000014	92.39	gold quality
rectum	UBERON:0001052	92.35	gold quality
bone marrow cell	CL:0002092	92.31	gold quality
right lung	UBERON:0002167	92.31	gold quality
metanephros cortex	UBERON:0010533	92.23	gold quality
bone marrow	UBERON:0002371	92.20	gold quality
skin of abdomen	UBERON:0001416	92.18	gold quality
lung	UBERON:0002048	90.84	gold quality
esophagus	UBERON:0001043	90.66	gold quality
heart left ventricle	UBERON:0002084	90.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting ARHGAP27, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-1293	96.16	64.69	916

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap27l	ENSDARG00000061798
danio_rerio	arhgap27	ENSDARG00000104255
mus_musculus	Arhgap27	ENSMUSG00000034255
rattus_norvegicus	Arhgap27	ENSRNOG00000028569
drosophila_melanogaster	RhoGAP16F	FBGN0030893
caenorhabditis_elegans		WBGENE00008006

Paralogs (3): ARHGAP15 (ENSG00000075884), ARHGAP9 (ENSG00000123329), ARHGAP12 (ENSG00000165322)

Protein

Protein identifiers

Rho GTPase-activating protein 27 — Q6ZUM4 (reviewed: Q6ZUM4)

Alternative names: CIN85-associated multi-domain-containing Rho GTPase-activating protein 1, Rho-type GTPase-activating protein 27, SH3 domain-containing protein 20

All UniProt accessions (7): Q6ZUM4, A0A0C4DGE6, A0A8I5KVA8, E9PIR1, E9PK18, E9PNT2, E9PNX6

UniProt curated annotations — full annotation on UniProt →

Function. Rho GTPase-activating protein which may be involved in clathrin-mediated endocytosis. GTPase activators for the Rho-type GTPases act by converting them to an inactive GDP-bound state. Has activity toward CDC42 and RAC1.

Subunit / interactions. Interacts with SH3KBP1/CIN85.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Expressed in germinal center B-cell, spleen, chronic lymphocytic leukemia, pancreatic cancer and lung cancer.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6ZUM4-1	1	yes
Q6ZUM4-2	2
Q6ZUM4-3	3
Q6ZUM4-4	4, SH3D20

RefSeq proteins (19): NP_001269219, NP_001372313, NP_001372314, NP_001372315, NP_001372316, NP_001372317, NP_001372318, NP_001372319, NP_001372320, NP_001372321, NP_001372322, NP_001372323, NP_001372324, NP_001372325, NP_001372326, NP_001372327, NP_001372328, NP_777579, NP_954976 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001202	WW_dom	Domain
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011047	Quinoprotein_ADH-like_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR050729	Rho-GAP	Family

Pfam: PF00169, PF00397, PF00620

UniProt features (39 total): modified residue 7, strand 7, domain 6, region of interest 4, splice variant 4, sequence conflict 3, helix 3, compositionally biased region 2, chain 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3PP2	X-RAY DIFFRACTION	1.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZUM4-F1	67.53	0.30

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): 733 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (7): 156, 216, 249, 347, 456, 461, 466

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 109 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, CHANDRAN_METASTASIS_DN, BILD_HRAS_ONCOGENIC_SIGNATURE, AML_Q6, GOBP_IMPORT_INTO_CELL, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_ENDOCYTOSIS, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOBP_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, SENGUPTA_EBNA1_ANTICORRELATED, GOMF_ENZYME_REGULATOR_ACTIVITY

GO Biological Process (7): receptor-mediated endocytosis (GO:0006898), small GTPase-mediated signal transduction (GO:0007264), Rho protein signal transduction (GO:0007266), regulation of small GTPase mediated signal transduction (GO:0051056), protein heterooligomerization (GO:0051291), endocytosis (GO:0006897), signal transduction (GO:0007165)

GO Molecular Function (4): GTPase activator activity (GO:0005096), SH3 domain binding (GO:0017124), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
small GTPase-mediated signal transduction	2
endocytosis	1
intracellular signaling cassette	1
regulation of intracellular signal transduction	1
protein complex oligomerization	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
protein domain specific binding	1
actin binding	1
protein-containing complex binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP27	SH3KBP1	Q96B97	687
ARHGAP27	KANSL1	Q7Z3B3	580
ARHGAP27	ARL17A	Q8IVW1	558
ARHGAP27	PLEKHM1	Q9Y4G2	554
ARHGAP27	LRRC37A2	A6NM11	542
ARHGAP27	ARL17B	I3L3L1	534
ARHGAP27	CDC42	P21181	513
ARHGAP27	LRRC37A	A6NMS7	507
ARHGAP27	LRRC37A3	O60309	506
ARHGAP27	SPPL2C	Q8IUH8	476
ARHGAP27	RHOA	P06749	458
ARHGAP27	CRHR1	P34998	446
ARHGAP27	TFRC	P02786	438
ARHGAP27	RDM1	Q8NG50	429
ARHGAP27	CLNK	Q7Z7G1	413

IntAct

9 interactions, top by confidence:

A	B	Type	Score
EPS8L1	DHPS	psi-mi:“MI:0914”(association)	0.530
ARHGAP27	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
EPS8L1	IDE	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
dmsB	ARHGAP27	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): ARHGAP27 (Affinity Capture-RNA), RAC1 (Biochemical Activity), CDC42 (Biochemical Activity), SH3KBP1 (Reconstituted Complex), ARHGAP27 (Affinity Capture-Western), ARHGAP27 (Two-hybrid), ARHGAP27 (Proximity Label-MS), ARHGAP27 (Affinity Capture-MS), ARHGAP27 (Affinity Capture-MS), ARHGAP27 (Affinity Capture-MS), ARHGAP27 (Affinity Capture-MS), ARHGAP27 (Proximity Label-MS), ARHGAP27 (Affinity Capture-MS)

ESM2 similar proteins: A0A8P0N4K0, A2AB59, B4F7F3, D3YZU1, D3ZD05, O35681, O75427, O95382, P22455, P22607, P40748, P55144, P70218, Q06418, Q14160, Q1LZH7, Q2PS20, Q32P44, Q495M9, Q4ACU6, Q4H4B6, Q505F5, Q5F488, Q61851, Q63ZY3, Q6P9K8, Q6TLK4, Q6ZUM4, Q7KRY7, Q80T11, Q80U72, Q8BH60, Q8BX02, Q8N1G4, Q8TE68, Q8VC03, Q8VHK1, Q8VHK2, Q8WXD9, Q8WXE0

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ARHGAP27	“down-regulates activity”	RAC1	“gtpase-activating protein”

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	116
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3063483	GRCh37/hg19 17q21.31(chr17:43459741-44292742)x1	Pathogenic

SpliceAI

3401 predictions. Top by Δscore:

Variant	Effect	Δscore
17:45395632:CC:C	acceptor_gain	1.0000
17:45395633:CC:C	acceptor_gain	1.0000
17:45395633:CCTGT:C	acceptor_loss	1.0000
17:45395634:C:CA	acceptor_loss	1.0000
17:45395634:C:CC	acceptor_gain	1.0000
17:45395738:GCTCA:G	donor_loss	1.0000
17:45395739:CTCAC:C	donor_loss	1.0000
17:45395740:TCA:T	donor_loss	1.0000
17:45395741:CACC:C	donor_loss	1.0000
17:45395742:A:AC	donor_gain	1.0000
17:45395742:A:AG	donor_loss	1.0000
17:45395743:C:A	donor_loss	1.0000
17:45395743:C:CC	donor_gain	1.0000
17:45395743:CCGG:C	donor_gain	1.0000
17:45395845:CAACT:C	acceptor_gain	1.0000
17:45395848:CT:C	acceptor_gain	1.0000
17:45395850:C:CC	acceptor_gain	1.0000
17:45395977:GCTCA:G	donor_loss	1.0000
17:45395978:CTCAC:C	donor_loss	1.0000
17:45395980:CA:C	donor_loss	1.0000
17:45395981:A:AC	donor_gain	1.0000
17:45395981:AC:A	donor_loss	1.0000
17:45395982:C:CG	donor_gain	1.0000
17:45395982:CTG:C	donor_gain	1.0000
17:45395982:CTGA:C	donor_gain	1.0000
17:45395985:ATGG:A	donor_gain	1.0000
17:45396040:C:CA	donor_gain	1.0000
17:45396113:CTCAT:C	acceptor_gain	1.0000
17:45396114:TCAT:T	acceptor_gain	1.0000
17:45396115:CAT:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000058743 (17:45406425 C>T), RS1000187656 (17:45403778 C>A,T), RS1000323868 (17:45408818 A>G), RS1000596159 (17:45423208 G>A), RS1000634956 (17:45416363 A>C), RS1000709277 (17:45418030 CTGTCTCAAAAAAAAAAAAAAAAAA>C), RS1000710863 (17:45399902 C>T), RS1000727387 (17:45403550 CA>C,CAA), RS1000882896 (17:45434743 G>A,C,T), RS1000894715 (17:45429028 C>T), RS1000901500 (17:45416640 C>T), RS1001068262 (17:45423023 A>G), RS1001238096 (17:45432824 C>G), RS1001416302 (17:45433020 C>G,T), RS1001464982 (17:45426775 C>T)

Disease associations

OMIM: gene MIM:610591 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004077_9	Cognitive function	1.000000e-07
GCST004902_11	Parkinson’s disease	1.000000e-68
GCST005038_99	Allergic disease (asthma, hay fever or eczema)	1.000000e-08
GCST005232_131	Neuroticism	8.000000e-26
GCST005831_4	Systemic lupus erythematosus	4.000000e-08
GCST006269_725	General cognitive ability	1.000000e-08
GCST006661_255	Male-pattern baldness	2.000000e-22
GCST007709_100	General factor of neuroticism	1.000000e-10
GCST007797_25	Asthma onset (childhood vs adult)	7.000000e-10
GCST007798_102	Asthma	6.000000e-07
GCST007800_70	Asthma (childhood onset)	6.000000e-20
GCST010002_124	Refractive error	8.000000e-16
GCST010083_15	Hemoglobin levels	3.000000e-51
GCST010226_10	Cortical surface area (global PC1)	8.000000e-28
GCST010703_91	Brain morphology (MOSTest)	2.000000e-65
GCST90002395_261	Mean platelet volume	5.000000e-23
GCST90020024_521	A body shape index	2.000000e-09
GCST90020025_1448	Waist-to-hip ratio adjusted for BMI	1.000000e-09
GCST90020027_420	Waist-hip index	2.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0007660	neuroticism measurement
EFO:0004847	age at onset
EFO:0004509	hemoglobin measurement
EFO:0008381	total cortical area measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
Air Pollutants	affects expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects cotreatment, affects expression, affects methylation	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
cupric chloride	increases expression	1
hydroquinone	increases expression	1
monomethylarsonous acid	increases expression	1
K 7174	increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects cotreatment, affects expression, affects methylation	1
Sunitinib	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Azathioprine	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Methapyrilene	decreases methylation	1
Ozone	increases abundance, affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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