ARHGAP36

Summary

ARHGAP36 (Rho GTPase activating protein 36, HGNC:26388) is a protein-coding gene on chromosome Xq26.1, encoding Rho GTPase-activating protein 36 (Q6ZRI8). GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Predicted to enable GTPase activator activity. Predicted to be involved in signal transduction.

Source: NCBI Gene 158763 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 121 total — 5 pathogenic
• MANE Select transcript: NM_144967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26388
Approved symbol	ARHGAP36
Name	Rho GTPase activating protein 36
Location	Xq26.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30058
Ensembl gene	ENSG00000147256
Ensembl biotype	protein_coding
OMIM	300937
Entrez	158763

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000276211, ENST00000370921, ENST00000370922, ENST00000412432, ENST00000423277, ENST00000639280

RefSeq mRNA: 3 — MANE Select: NM_144967 NM_001282607, NM_001330651, NM_144967

CCDS: CCDS14628, CCDS65320, CCDS83489

Canonical transcript exons

ENST00000276211 — 12 exons

Exon	Start	End
ENSE00000979387	131084215	131084407
ENSE00000979388	131084626	131084681
ENSE00000979389	131084914	131085064
ENSE00000979390	131085588	131085736
ENSE00000979391	131085913	131086089
ENSE00000979392	131086329	131086426
ENSE00001095508	131086559	131086665
ENSE00001095509	131088628	131089885
ENSE00001095511	131083734	131083969
ENSE00001374864	131083165	131083230
ENSE00001382851	131058346	131058444
ENSE00001384225	131081524	131081918

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 98.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3425 / max 295.4748, expressed in 26 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197557	0.2864	16
197556	0.0318	7
197566	0.0243	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.08	gold quality
pituitary gland	UBERON:0000007	96.81	gold quality
adenohypophysis	UBERON:0002196	94.71	gold quality
hypothalamus	UBERON:0001898	88.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.59	gold quality
superior vestibular nucleus	UBERON:0007227	85.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.24	gold quality
tibialis anterior	UBERON:0001385	76.55	silver quality
nucleus accumbens	UBERON:0001882	73.76	gold quality
amygdala	UBERON:0001876	72.41	gold quality
gastrocnemius	UBERON:0001388	69.32	gold quality
medulla oblongata	UBERON:0001896	69.08	gold quality
endothelial cell	CL:0000115	67.66	gold quality
muscle of leg	UBERON:0001383	67.30	gold quality
deltoid	UBERON:0001476	66.36	silver quality
hindlimb stylopod muscle	UBERON:0004252	65.97	gold quality
anterior cingulate cortex	UBERON:0009835	65.96	gold quality
spinal cord	UBERON:0002240	64.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.36	gold quality
forebrain	UBERON:0001890	64.23	gold quality
prefrontal cortex	UBERON:0000451	62.99	gold quality
temporal lobe	UBERON:0001871	62.86	gold quality
adrenal gland	UBERON:0002369	62.65	gold quality
right adrenal gland	UBERON:0001233	62.48	gold quality
Ammon’s horn	UBERON:0001954	61.27	gold quality
brain	UBERON:0000955	61.13	gold quality
caudate nucleus	UBERON:0001873	60.77	gold quality
ventricular zone	UBERON:0003053	59.70	gold quality
substantia nigra	UBERON:0002038	59.56	gold quality
ventral tegmental area	UBERON:0002691	59.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting ARHGAP36, 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-4673	100.00	66.64	1490
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-642A-3P	99.23	67.67	1258

Literature-anchored findings (GeneRIF, showing 5)

• ARHGAP36 isoforms capable of Gli activation are up-regulated in a subset of human medulloblastomas. (PMID:25024229)
• a new mechanism of Gli transcription factor activation and implicate ARHGAP36 dysregulation in the onset and/or progression of GLI-dependent cancers. (PMID:25024229)
• We have reported here for the first time a reduced activity of both Rac1 and Cdc42 in human pheochromocytoma resection as well as tumor-associated expression changes of FARP1, ARHGEF1, and ARHGAP36 (PMID:26911374)
• PKA inhibition by ARHGAP36 promotes derepression of the Hedgehog signalling pathway, thereby providing a simple rationale for the upregulation of ARHGAP36 in medulloblastoma. (PMID:27713425)
• Structure-activity mapping of ARHGAP36 reveals regulatory roles for its GAP homology and C-terminal domains. (PMID:33999959)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap36	ENSDARG00000059672
mus_musculus	Arhgap36	ENSMUSG00000036198
rattus_norvegicus	Arhgap36	ENSRNOG00000007552
drosophila_melanogaster	RhoGAP102A	FBGN0259216
caenorhabditis_elegans	rga-6	WBGENE00015303

Paralogs (1): ARHGAP6 (ENSG00000047648)

Protein

Protein identifiers

Rho GTPase-activating protein 36 — Q6ZRI8 (reviewed: Q6ZRI8)

All UniProt accessions (3): Q6ZRI8, A0A2X0TVT1, X6RIA0

UniProt curated annotations — full annotation on UniProt →

Function. GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Subunit / interactions. May interacts (via the Rho-GAP domain) with the active form of RAC1.

Tissue specificity. Detected in the outer root sheath of hair follicles at the level of the stem cell bulge, during the anagen and telogen phases of hair growth (at protein level).

Disease relevance. Bazex-Dupre-Christol syndrome (BDCS) [MIM:301845] An X-linked dominant disorder characterized by a triad of congenital hypotrichosis, follicular atrophoderma affecting the dorsa of the hands and feet, the face and extensor surfaces of the elbows or knees, and the development of basocellular neoplasms including basal cell nevi and basal cell carcinomas from the second decade onwards. Other reported features include associated hair shaft abnormalities (pili torti and trichorrhexis nodosa) admixed with hypotrichosis, prominent milia affecting the face, hypohidrosis, pinched nose with hypoplastic nasal alae and prominent columella, atopic diathesis with comedones, keratosis pilaris, joint hypermobility, lingua plicata and hyperpigmentation of the forehead. The gene represented in this entry may be involved in disease pathogenesis. In patients with Bazex-Dupre-Christol syndrome, ARHGAP36 is overexpressed in hair follicles during telogen, in basal cell carcinomas, and in trichoepitheliomas. This is due to small duplications in an intergenic region on chromosome Xq26 that harbor non-coding enhancer elements that control ARHGAP36 expression, and are responsible for disease development.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6ZRI8-1	1	yes
Q6ZRI8-2	2
Q6ZRI8-3	3
Q6ZRI8-4	4
Q6ZRI8-5	5

RefSeq proteins (3): NP_001269536, NP_001317580, NP_659404* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR037863	RHOGAP6/36	Family
IPR041852	ARHGAP6_RhoGAP	Domain

Pfam: PF00620

UniProt features (11 total): splice variant 4, signal peptide 1, chain 1, sequence conflict 1, domain 1, region of interest 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZRI8-F1	68.40	0.26

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

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): MYAATNNNNNNNGGC_UNKNOWN, E2F_Q4_01, GCANCTGNY_MYOD_Q6, CHX10_01, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, MYOD_01, ROZANOV_MMP14_TARGETS_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, AACTTT_UNKNOWN, WHN_B, E12_Q6, ATGTCAC_MIR489, E2F_Q6_01

GO Biological Process (3): actin filament organization (GO:0007015), signal transduction (GO:0007165), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (1): GTPase activator activity (GO:0005096)

GO Cellular Component (2): actin cytoskeleton (GO:0015629), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin cytoskeleton organization	1
supramolecular fiber organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
positive regulation of signal transduction	1
intracellular signal transduction	1
regulation of intracellular signal transduction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
cytoskeleton	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP36	OR5AK2	Q8NH90	629
ARHGAP36	UTS2B	Q765I0	459
ARHGAP36	VWC2	Q2TAL6	455
ARHGAP36	PHAF1	Q9BSU1	447
ARHGAP36	FRMD7	Q6ZUT3	444
ARHGAP36	ZNF311	Q5JNZ3	418
ARHGAP36	TEDC2	Q7L2K0	400
ARHGAP36	ARHGEF39	Q8N4T4	397
ARHGAP36	TMEM161B	Q8NDZ6	393
ARHGAP36	FAM163B	P0C2L3	391
ARHGAP36	ZNF333	Q96JL9	387
ARHGAP36	MEF2C	Q06413	383
ARHGAP36	MBOAT4	Q96T53	373
ARHGAP36	BBX	Q8WY36	365
ARHGAP36	POU6F1	Q14863	362

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ARHGAP36	PJA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (126): PREPL (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), APOD (Affinity Capture-MS), ATG2B (Affinity Capture-MS), TTC19 (Affinity Capture-MS), PJA2 (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), CLU (Affinity Capture-MS), PTPRD (Affinity Capture-MS), STOM (Affinity Capture-MS), MUCL1 (Affinity Capture-MS), CAND2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), ADCK3 (Affinity Capture-MS), API5 (Affinity Capture-MS)

ESM2 similar proteins: A1L1R5, A2A3K4, A7E379, A7KAX9, A7MB27, A8WRJ2, B1AUC7, B9FS74, D2H9U0, G3X9J0, G5EFI8, H2KZH5, I2HAA0, O14827, O16844, O43147, O43182, O54834, O95696, P27671, Q20498, Q21341, Q292S8, Q2KHT3, Q2NKQ1, Q3V0G7, Q4G017, Q5VVW2, Q60610, Q64512, Q69ZH9, Q6GPD0, Q6ING4, Q6NUB7, Q6ZRI8, Q803Q4, Q80TM9, Q80U12, Q80U30, Q810W7

Diamond homologs: A0A0G2JTR4, A2AB59, A6X8Z5, A7MB27, B1AUC7, B2RTY4, D2H9U0, E9Q6X9, O43182, O54834, P17121, P34288, P42331, Q12979, Q2M1Z3, Q54J98, Q54TH9, Q55DW9, Q5SSL4, Q5U2Z7, Q6ZRI8, Q8AVG0, Q8BYW1, Q8C170, Q8C4V1, Q9VIS1, Q9VTU3, Q9Z1N3, A4II46, A6QNS3, E7F3F0, O94988, P35688, P98171, Q5T5U3, Q6DFV3, Q6TLK4, Q6ZUM4, Q7Z5H3, Q8BL80

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1199401	GRCh37/hg19 Xq26.1-26.2(chrX:130085469-130482969)x0	Pathogenic
1710922	GRCh37/hg19 Xq26.1-26.2(chrX:129711889-132794615)x3	Pathogenic
253469	GRCh37/hg19 Xq26.1-26.2(chrX:129796796-132686500)x0	Pathogenic
253532	GRCh37/hg19 Xq26.1-26.2(chrX:129760788-132675352)x0	Pathogenic
57988	GRCh38/hg38 Xq26.1-26.2(chrX:131042072-131826589)x1	Pathogenic

SpliceAI

1746 predictions. Top by Δscore:

Variant	Effect	Δscore
X:131081916:GAG:G	donor_gain	1.0000
X:131081918:GGTA:G	donor_loss	1.0000
X:131081919:G:GC	donor_loss	1.0000
X:131081920:T:A	donor_loss	1.0000
X:131083226:GAGGG:G	donor_gain	1.0000
X:131083721:C:CA	acceptor_gain	1.0000
X:131083723:T:TA	acceptor_gain	1.0000
X:131083724:G:A	acceptor_gain	1.0000
X:131083730:CCA:C	acceptor_loss	1.0000
X:131083732:A:AC	acceptor_loss	1.0000
X:131083732:A:AG	acceptor_gain	1.0000
X:131083732:AGCT:A	acceptor_gain	1.0000
X:131083733:G:A	acceptor_loss	1.0000
X:131083733:G:GG	acceptor_gain	1.0000
X:131083733:GCT:G	acceptor_gain	1.0000
X:131083733:GCTG:G	acceptor_gain	1.0000
X:131083733:GCTGT:G	acceptor_gain	1.0000
X:131083945:G:GT	donor_gain	1.0000
X:131083965:GTCGA:G	donor_gain	1.0000
X:131083968:GA:G	donor_gain	1.0000
X:131083970:G:GG	donor_gain	1.0000
X:131083975:T:G	donor_gain	1.0000
X:131084213:AG:A	acceptor_gain	1.0000
X:131084214:GG:G	acceptor_gain	1.0000
X:131084331:GAAGA:G	donor_gain	1.0000
X:131084335:A:G	donor_gain	1.0000
X:131084620:TTTCA:T	acceptor_loss	1.0000
X:131084624:A:AG	acceptor_gain	1.0000
X:131084625:G:GG	acceptor_gain	1.0000
X:131084680:AGGT:A	donor_loss	1.0000

AlphaMissense

3559 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:131081853:T:C	L63P	0.996
X:131081844:G:C	R60P	0.994
X:131085663:T:C	L344P	0.990
X:131085675:T:C	L348P	0.990
X:131085947:C:A	A380D	0.990
X:131081865:C:A	A67D	0.989
X:131084990:T:C	L294P	0.989
X:131084375:T:A	V239D	0.988
X:131085672:T:C	L347P	0.988
X:131085920:G:A	G371D	0.986
X:131085684:T:C	L351P	0.985
X:131086084:T:C	F426L	0.985
X:131086086:C:A	F426L	0.985
X:131086086:C:G	F426L	0.985
X:131084981:C:A	A291D	0.984
X:131084998:T:C	F297L	0.984
X:131085000:T:A	F297L	0.984
X:131085000:T:G	F297L	0.984
X:131081853:T:A	L63Q	0.983
X:131086405:G:C	R453P	0.983
X:131081843:C:A	R60S	0.982
X:131085929:T:C	M374T	0.981
X:131081877:T:C	L71P	0.980
X:131081864:G:C	A67P	0.979
X:131084383:T:C	C242R	0.979
X:131084987:T:C	L293P	0.979
X:131085924:C:A	N372K	0.978
X:131085924:C:G	N372K	0.978
X:131084385:C:G	C242W	0.977
X:131085618:T:C	L329P	0.977

dbSNP variants (sampled 300 via entrez): RS1000013918 (X:131080593 C>G), RS1000066382 (X:131079901 T>C), RS1000153000 (X:131068504 A>C), RS1000328106 (X:131086275 A>G), RS1000576175 (X:131070734 G>T), RS1000715574 (X:131058591 G>A), RS1000861186 (X:131059266 G>T), RS1000994142 (X:131070087 C>A), RS1001068627 (X:131082460 G>A), RS1001074939 (X:131083652 G>A,C), RS1001641939 (X:131058110 C>T), RS1001857048 (X:131081959 G>A), RS1001859547 (X:131061379 C>A), RS1001929352 (X:131063667 C>G), RS1002044651 (X:131069962 G>A)

Disease associations

OMIM: gene MIM:300937 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	2
Estradiol	affects binding, increases expression	2
securinine	decreases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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