AGAP9

Summary

AGAP9 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 9, HGNC:23463) is a protein-coding gene on chromosome 10q11.22, encoding Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 9 (Q5VTM2). Putative GTPase-activating protein. It is a selective cancer dependency (DepMap: 17.0% of cell lines).

Predicted to enable GTPase activator activity and GTPase activity.

Source: NCBI Gene 642517 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 18 total — 3 pathogenic, 3 likely-pathogenic
• Cancer dependency (DepMap): dependent in 17.0% of screened cell lines
• MANE Select transcript: NM_001190810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23463
Approved symbol	AGAP9
Name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 9
Location	10q11.22
Locus type	gene with protein product
Status	Approved
Aliases	bA301J7.2, FLJ00312
Ensembl gene	ENSG00000204172
Ensembl biotype	protein_coding
OMIM	621158
Entrez	642517

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000452145

RefSeq mRNA: 1 — MANE Select: NM_001190810 NM_001190810

CCDS: CCDS73125

Canonical transcript exons

ENST00000452145 — 8 exons

Exon	Start	End
ENSE00002434484	47504189	47504240
ENSE00002441710	47520499	47520567
ENSE00002453062	47523304	47523638
ENSE00002466142	47510171	47510271
ENSE00002506489	47522866	47522934
ENSE00002523823	47517823	47517857
ENSE00002523831	47501854	47503543
ENSE00003521440	47507548	47507583

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 88.96.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.96	gold quality
right lobe of liver	UBERON:0001114	88.27	gold quality
body of pancreas	UBERON:0001150	88.16	gold quality
pituitary gland	UBERON:0000007	88.15	gold quality
apex of heart	UBERON:0002098	88.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.80	gold quality
adenohypophysis	UBERON:0002196	86.70	gold quality
cerebellar hemisphere	UBERON:0002245	86.66	gold quality
cerebellar cortex	UBERON:0002129	86.55	gold quality
right testis	UBERON:0004534	86.52	gold quality
cerebellum	UBERON:0002037	86.48	gold quality
mucosa of stomach	UBERON:0001199	86.17	gold quality
lower esophagus mucosa	UBERON:0035834	85.88	gold quality
left testis	UBERON:0004533	85.83	gold quality
body of stomach	UBERON:0001161	85.51	gold quality
duodenum	UBERON:0002114	85.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.37	gold quality
fundus of stomach	UBERON:0001160	85.18	gold quality
right lobe of thyroid gland	UBERON:0001119	85.10	gold quality
testis	UBERON:0000473	85.01	gold quality
left lobe of thyroid gland	UBERON:0001120	84.73	gold quality
small intestine	UBERON:0002108	84.33	gold quality
thyroid gland	UBERON:0002046	84.32	gold quality
skin of leg	UBERON:0001511	84.30	gold quality
left ovary	UBERON:0002119	84.21	gold quality
zone of skin	UBERON:0000014	84.07	gold quality
skin of abdomen	UBERON:0001416	84.07	gold quality
ectocervix	UBERON:0012249	83.92	gold quality
substantia nigra	UBERON:0002038	83.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.66
E-GEOD-110499	no	683.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting AGAP9, 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-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-8080	99.82	67.52	1342
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-223-5P	99.24	68.82	1206
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-4661-5P	93.34	67.13	400

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.0% 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), AGAP6 (ENSG00000204149), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 9 — Q5VTM2 (reviewed: Q5VTM2)

Alternative names: Centaurin-gamma-like family member 6

All UniProt accessions (1): Q5VTM2

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.

Similarity. Belongs to the centaurin gamma-like family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VTM2-1	1	yes
Q5VTM2-2	2

RefSeq proteins (1): NP_001177739* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	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

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTM2-F1	63.02	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (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, MIR5010_3P, MIR6801_5P, MIR10393_3P, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, GOMF_GTPASE_ACTIVATOR_ACTIVITY, chr10q11

GO Biological Process (0):

GO Molecular Function (4): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), 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
cation binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

1 interactions, top by confidence:

BioGRID (2): AGAP9 (Affinity Capture-MS), AGAP9 (Negative Genetic)

ESM2 similar proteins: A6NIR3, A7J1T0, A7J1T2, A7KAX9, A7MBB4, A8JQ65, A8XQD5, B3LXF2, B3NYS4, B4I4Y1, B4JHJ7, B4K6T8, B4PRE2, B4R0A5, F4J394, F4JZ68, G5EFI8, O01700, O43283, P14270, Q01583, Q08499, Q14693, Q1HKZ5, Q2NKQ1, Q5R8X7, Q5VTM2, Q5VUJ5, Q5VW22, Q66HD5, Q6GPD0, Q6IVY4, Q6NN85, Q6NRL1, Q811P8, Q8BFX3, Q8BPQ7, Q8BXK8, Q8CI96, Q8N3C7

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q2TA45, Q3MID3, Q3UHD9, Q4KLH5, Q4KLN7, Q4LDD4, Q4R4C9, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	4
Likely benign	1
Benign	7

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
57411	GRCh38/hg38 10q11.22-11.23(chr10:45999930-49937908)x3	Pathogenic
625591	GRCh37/hg19 10q11.22-11.23(chr10:48102606-50641752)	Pathogenic
689042	GRCh37/hg19 10q11.22-11.23(chr10:48106368-51250418)x1	Pathogenic
149971	GRCh38/hg38 10q11.22-11.23(chr10:45931517-49929364)x1	Likely pathogenic
150503	GRCh38/hg38 10q11.22-11.23(chr10:45999930-49937908)x1	Likely pathogenic
980914	GRCh37/hg19 10q11.22-11.23(chr10:47132305-51627470)x1	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4359 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1047435 (10:47502436 A>C,G,T), RS1047447 (10:47502343 T>C), RS1047466 (10:47502248 T>C,G), RS1047615 (10:47501918 A>G), RS1047621 (10:47501913 T>C,G), RS1047630 (10:47501906 T>C), RS1064075 (10:47501925 T>A), RS112195966 (10:47517008 G>T), RS112567241 (10:47513284 C>T), RS112708772 (10:47515472 C>A), RS112768968 (10:47521573 A>T), RS1137834 (10:47524904 C>T), RS1137837 (10:47524598 A>C,G), RS1156253196 (10:47516150 C>CT), RS1156310743 (10:47514523 C>A,G)

Disease associations

OMIM: gene MIM:621158 | 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
GCST007637_50	Diffusing capacity of carbon monoxide	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009369	diffusing capacity of the lung for carbon monoxide

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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