AGAP6

Summary

AGAP6 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 6, HGNC:23466) is a protein-coding gene on chromosome 10q11.23, encoding Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (Q5VW22). Putative GTPase-activating protein. It is a selective cancer dependency (DepMap: 72.9% of cell lines).

Predicted to enable GTPase activator activity and GTPase activity.

Source: NCBI Gene 414189 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 154 total — 2 pathogenic, 3 likely-pathogenic
• Cancer dependency (DepMap): dependent in 72.9% of screened cell lines
• MANE Select transcript: NM_001077665

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23466
Approved symbol	AGAP6
Name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 6
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Aliases	bA324H6.1
Ensembl gene	ENSG00000204149
Ensembl biotype	protein_coding
OMIM	621157
Entrez	414189

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000311652, ENST00000374056, ENST00000412531, ENST00000618025, ENST00000618171, ENST00000679578, ENST00000679610, ENST00000679810, ENST00000680115, ENST00000681530

RefSeq mRNA: 1 — MANE Select: NM_001077665 NM_001077665

CCDS: CCDS44397

Canonical transcript exons

ENST00000412531 — 8 exons

Exon	Start	End
ENSE00002440285	50004685	50004720
ENSE00002440994	49994395	49994429
ENSE00002461303	49991676	49991744
ENSE00002480303	50008711	50010499
ENSE00002498744	49989308	49989376
ENSE00002510883	50008025	50008076
ENSE00002520888	50001996	50002096
ENSE00003719818	49988406	49988938

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 91.14.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	91.14	gold quality
adenohypophysis	UBERON:0002196	91.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.67	gold quality
cerebellar hemisphere	UBERON:0002245	90.38	gold quality
cerebellar cortex	UBERON:0002129	90.34	gold quality
cerebellum	UBERON:0002037	90.26	gold quality
right lobe of liver	UBERON:0001114	89.65	gold quality
granulocyte	CL:0000094	88.84	gold quality
spleen	UBERON:0002106	88.50	gold quality
left lobe of thyroid gland	UBERON:0001120	87.81	gold quality
right testis	UBERON:0004534	87.77	gold quality
body of pancreas	UBERON:0001150	87.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.49	gold quality
left testis	UBERON:0004533	87.38	gold quality
right lobe of thyroid gland	UBERON:0001119	87.30	gold quality
lower esophagus mucosa	UBERON:0035834	87.21	gold quality
thyroid gland	UBERON:0002046	87.14	gold quality
fundus of stomach	UBERON:0001160	86.86	gold quality
metanephros cortex	UBERON:0010533	86.81	gold quality
testis	UBERON:0000473	86.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.39	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.34	gold quality
prostate gland	UBERON:0002367	85.99	gold quality
apex of heart	UBERON:0002098	85.97	gold quality
endocervix	UBERON:0000458	85.90	gold quality
left uterine tube	UBERON:0001303	85.79	gold quality
right frontal lobe	UBERON:0002810	85.78	gold quality
body of stomach	UBERON:0001161	85.76	gold quality
primary visual cortex	UBERON:0002436	85.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	22.38
E-ANND-3	no	0.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting AGAP6, 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-4682	100.00	68.89	1258
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.9% of screened cell lines.

Cross-species orthologs

0 orthologs

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), ACAP3 (ENSG00000131584), AGAP3 (ENSG00000133612), AGAP2 (ENSG00000135439), APPL2 (ENSG00000136044), GIT2 (ENSG00000139436), ARFGAP2 (ENSG00000149182), ASAP2 (ENSG00000151693), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 — Q5VW22 (reviewed: Q5VW22)

Alternative names: Centaurin-gamma-like family member 3

All UniProt accessions (4): Q5VW22, A0A087WSV4, A0A7P0T8Q0, A0A7P0T9P6

UniProt curated annotations — full annotation on UniProt →

Function. Putative GTPase-activating protein.

Miscellaneous. Encoded by one of the numerous copies of centaurin gamma-like genes clustered in the q11 region of chromosome 10. Prediction based on family homologs sequence.

Similarity. Belongs to the centaurin gamma-like family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VW22-1	1	yes
Q5VW22-2	2

RefSeq proteins (1): NP_001071133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR001849	PH_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR051282	Arf-GAP_GTPase_ANK_PH	Family

Pfam: PF01412, PF12796

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VW22-F1	63.73	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 19 (showing top): GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIR607, MIR5010_3P, MIR377_3P, MIR6801_5P, MIR10393_3P, BLANCO_MELO_COVID19_SARS_COV_2_INFECTION_A594_ACE2_EXPRESSING_CELLS_RUXOLITINIB_UP, THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_28DY_DN, THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_7DY_DN, QI_PBMC_ZOSTAVAX_AGE_50_75YO_CORRELATED_WITH_CONTRACTION_OF_VZV_SPECIFIC_T_CELLS_PEAK_TO_28DYAT_1DY_NEGATIVE, KANNAN_BLOOD_2012_2013_TIV_AGE_65PLS_REVACCINATED_IN_6_9_MO_VS_REVACCINATED_IN_12_13_MOS_DN

GO Biological Process (0):

GO Molecular Function (5): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGAP6	ANTXRL	A6NF34	507
AGAP6	FAM25A	B3EWG3	480
AGAP6	ZNF620	Q6ZNG0	474
AGAP6	TMEM273	Q5T292	448
AGAP6	ASAH2B	P0C7U1	448
AGAP6	LRRC18	Q8N456	447
AGAP6	FRMPD2	Q68DX3	436
AGAP6	VSTM4	Q8IW00	430
AGAP6	ARMC12	Q5T9G4	413
AGAP6	ANKRD31	Q8N7Z5	400
AGAP6	PTPN20	Q4JDL3	397
AGAP6	A0A096LNH4	A0A096LNH4	396
AGAP6	AHDC1	Q5TGY3	380
AGAP6	SYT15	Q9BQS2	380
AGAP6	NPIPA5	E9PKD4	377

IntAct

0 interactions, top by confidence:

BioGRID (6): AGAP6 (Affinity Capture-MS), AGAP6 (Co-fractionation), AGAP6 (Co-fractionation), AGAP6 (Co-fractionation), AGAP6 (Co-fractionation), AGAP6 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1W2PPD8, A1A5Q5, A2A3K4, A4H5X5, A7E379, B2RXH2, C0SUT9, D3ZKV9, F5HB62, O19132, O36371, O54705, O60291, O75164, O94953, P03177, P33802, P35228, Q1HVD1, Q29RJ0, Q3KSQ2, Q3U2K5, Q3UPF5, Q53WJ1, Q5R4R7, Q5R978, Q5RD88, Q5VW22, Q5VWQ0, Q6B0I6, Q6EEF3, Q6EMB2, Q6PI47, Q6X4W1, Q80T69, Q80TL4, Q8BFX3, Q8BW72, Q8CHB8, Q8K3Y6

Diamond homologs: A0A8V8TMC4, A6NIR3, D3YUJ3, P0C7X3, P34624, Q08CI4, Q28EL0, Q4R871, Q5T2Q4, Q5U5D0, Q5VUJ5, Q5VW22, Q6NRF4, Q8BGU5, Q8N7R7, Q8ND76, Q96P64, A1L520, A1Z7A6, A5PK26, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	135
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2663790	NC_000010.10:g.(?49383876)(52383915_?)del	Pathogenic
58551	GRCh38/hg38 10q11.22-11.23(chr10:45931517-50655311)x1	Pathogenic
1807813	GRCh37/hg19 10q11.22-11.23(chr10:48252675-51861565)x1	Likely pathogenic
394957	GRCh37/hg19 10q11.22-11.23(chr10:49392896-52372011)x3	Likely pathogenic
974738	NC_000010.10:g.49033586_52417694del	Likely pathogenic

SpliceAI

1200 predictions. Top by Δscore:

Variant	Effect	Δscore
10:49988937:AG:A	donor_loss	1.0000
10:49988938:GGTG:G	donor_loss	1.0000
10:49988940:T:A	donor_loss	1.0000
10:49989298:A:AG	acceptor_gain	1.0000
10:49989299:T:G	acceptor_gain	1.0000
10:49989300:A:AG	acceptor_gain	1.0000
10:49989373:GAAG:G	donor_gain	1.0000
10:49989374:AAGG:A	donor_loss	1.0000
10:49989375:AGGT:A	donor_loss	1.0000
10:49989376:GGT:G	donor_loss	1.0000
10:49989377:G:T	donor_loss	1.0000
10:49989378:T:A	donor_loss	1.0000
10:49991665:T:A	acceptor_gain	1.0000
10:49991667:T:TA	acceptor_gain	1.0000
10:49991671:T:G	acceptor_gain	1.0000
10:49991674:A:AG	acceptor_gain	1.0000
10:49991675:G:GG	acceptor_gain	1.0000
10:49991741:GATG:G	donor_gain	1.0000
10:49994393:A:AG	acceptor_gain	1.0000
10:49994394:G:GG	acceptor_gain	1.0000
10:49994394:GTT:G	acceptor_gain	1.0000
10:50001990:CTTCA:C	acceptor_loss	1.0000
10:50001992:TCA:T	acceptor_loss	1.0000
10:50001994:A:T	acceptor_loss	1.0000
10:50001995:G:A	acceptor_loss	1.0000
10:50002092:ATATC:A	donor_gain	1.0000
10:50002097:G:GG	donor_gain	1.0000
10:50003540:C:G	donor_gain	1.0000
10:50004683:A:AG	acceptor_gain	1.0000
10:50004684:G:GA	acceptor_gain	1.0000

AlphaMissense

4550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:50009392:T:C	F400L	0.936
10:50009394:T:A	F400L	0.936
10:50009394:T:G	F400L	0.936
10:50009039:T:A	V282D	0.933
10:50008980:A:C	K262N	0.921
10:50008980:A:T	K262N	0.921
10:50009356:T:C	F388L	0.913
10:50009358:T:A	F388L	0.913
10:50009358:T:G	F388L	0.913
10:50009425:T:A	W411R	0.913
10:50009425:T:C	W411R	0.913
10:50009851:T:C	F553L	0.904
10:50009853:T:A	F553L	0.904
10:50009853:T:G	F553L	0.904
10:50009417:G:C	R408P	0.901
10:50009427:G:C	W411C	0.899
10:50009427:G:T	W411C	0.899
10:50009835:A:C	K547N	0.888
10:50009835:A:T	K547N	0.888
10:50009357:T:C	F388S	0.876
10:50008998:G:C	K268N	0.875
10:50008998:G:T	K268N	0.875
10:50009434:G:C	A414P	0.873
10:50009823:G:C	W543C	0.854
10:50009823:G:T	W543C	0.854
10:50009450:T:C	I419T	0.852
10:50009821:T:A	W543R	0.850
10:50009821:T:C	W543R	0.850
10:50009393:T:C	F400S	0.848
10:50009063:T:A	L290H	0.839

dbSNP variants (sampled 300 via entrez): RS1059725 (10:50007111 G>A), RS1060727 (10:49987608 C>A), RS111421022 (10:50008355 A>G), RS111451326 (10:49992434 C>G,T), RS111587855 (10:49988136 A>G), RS111680887 (10:49998894 C>T), RS111723427 (10:49998026 C>T), RS112358790 (10:49997211 C>T), RS112373017 (10:50003748 C>T), RS112397344 (10:49997473 G>A), RS112634617 (10:49988637 C>A,G,T), RS112660776 (10:49998476 T>C), RS113006372 (10:50005988 T>A), RS113234838 (10:50008914 CAA>C), RS113243607 (10:50009811 G>A)

Disease associations

OMIM: gene MIM:621157 | disease phenotypes: MIM:133540

GenCC curated gene-disease

Mondo (2): Cockayne syndrome type 2 (MONDO:0019570), megacolon (MONDO:0001273)

Orphanet (2): Cockayne syndrome (Orphanet:191), Cockayne syndrome type 2 (Orphanet:90322)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
zinc chromate	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
abrine	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
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04340856	Not specified	COMPLETED	Retrospective, Uncontrolled Cohort Study on the Therapy of Chronic Megalon
NCT07470892	Not specified	NOT_YET_RECRUITING	Preoperative Fish Oil PN and Prognosis After Constipation Surgery