AGAP5

Summary

AGAP5 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 5, HGNC:23467) is a protein-coding gene on chromosome 10q22.2, encoding Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 5 (A6NIR3). Putative GTPase-activating protein. It is a selective cancer dependency (DepMap: 80.6% of cell lines).

Predicted to enable GTPase activator activity and GTPase activity.

Source: NCBI Gene 729092 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 127 total
• Cancer dependency (DepMap): dependent in 80.6% of screened cell lines
• MANE Select transcript: NM_001144000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23467
Approved symbol	AGAP5
Name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 5
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	Em:AC073389.1
Ensembl gene	ENSG00000172650
Ensembl biotype	protein_coding
OMIM	621156
Entrez	729092

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000374094, ENST00000443782, ENST00000607663

RefSeq mRNA: 1 — MANE Select: NM_001144000 NM_001144000

CCDS: CCDS44439

Canonical transcript exons

ENST00000374094 — 8 exons

Exon	Start	End
ENSE00001663819	73674295	73676074
ENSE00003493653	73697095	73697163
ENSE00003536518	73676719	73676770
ENSE00003612965	73692043	73692077
ENSE00003645100	73680071	73680106
ENSE00003650132	73682694	73682794
ENSE00003688909	73694736	73694804
ENSE00003737171	73697533	73698109

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 87.62.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	87.62	gold quality
right testis	UBERON:0004534	86.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.58	gold quality
left testis	UBERON:0004533	86.34	gold quality
testis	UBERON:0000473	85.74	gold quality
right uterine tube	UBERON:0001302	85.14	gold quality
apex of heart	UBERON:0002098	83.80	gold quality
right lobe of liver	UBERON:0001114	83.19	gold quality
endometrium	UBERON:0001295	83.06	gold quality
right ovary	UBERON:0002118	82.95	gold quality
skin of leg	UBERON:0001511	82.42	gold quality
pituitary gland	UBERON:0000007	82.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.33	gold quality
left ovary	UBERON:0002119	82.07	gold quality
zone of skin	UBERON:0000014	82.06	gold quality
fundus of stomach	UBERON:0001160	81.98	gold quality
right adrenal gland cortex	UBERON:0035827	81.93	gold quality
right lobe of thyroid gland	UBERON:0001119	81.88	gold quality
right adrenal gland	UBERON:0001233	81.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.74	gold quality
body of stomach	UBERON:0001161	81.69	gold quality
metanephros cortex	UBERON:0010533	81.67	gold quality
cerebellar hemisphere	UBERON:0002245	81.59	gold quality
cerebellar cortex	UBERON:0002129	81.56	gold quality
skin of abdomen	UBERON:0001416	81.54	gold quality
minor salivary gland	UBERON:0001830	81.54	gold quality
ovary	UBERON:0000992	81.48	gold quality
cerebellum	UBERON:0002037	81.44	gold quality
left adrenal gland cortex	UBERON:0035825	81.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6075	no	328.25
E-ANND-3	no	1.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting AGAP5, 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-548C-3P	99.99	74.01	7587
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-3671	99.90	73.04	3897
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4428	99.73	66.41	1733
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-873-3P	96.84	66.09	786
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-4661-5P	93.34	67.13	400

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.6% 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), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 5 — A6NIR3 (reviewed: A6NIR3)

Alternative names: Centaurin-gamma-like family member 2

All UniProt accessions (3): A6NIR3, J3KQL4, U3KQ60

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.

RefSeq proteins (1): NP_001137472* (*=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, sequence conflict 3, region of interest 3, domain 2, repeat 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NIR3-F1	62.80	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (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, ZNF8_TARGET_GENES, MIR607, MIR5010_3P, MIR377_3P, MIR6801_5P, MIR10393_3P, DESCARTES_FETAL_SPLEEN_AFP_ALB_POSITIVE_CELLS, ZNF697_TARGET_GENES, ZNF426_TARGET_GENES, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY

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

172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGAP5	FAM241A	Q8N8J7	521
AGAP5	HDHD3	Q9BSH5	475
AGAP5	MYOZ1	Q9NP98	418
AGAP5	ZPLD1	Q8TCW7	417
AGAP5	TLL2	Q9Y6L7	401
AGAP5	Q05D86	Q05D86	400
AGAP5	PLEKHS1	Q5SXH7	396
AGAP5	KIF27	Q86VH2	393
AGAP5	SYNPO2L	Q9H987	374
AGAP5	POFUT4	Q495W5	358
AGAP5	KDELR3	O43731	355
AGAP5	WDR74	Q6RFH5	351
AGAP5	PLCL2	Q9UPR0	350
AGAP5	ANKRD53	Q8N9V6	348
AGAP5	GTF2H2C	Q6P1K8	348

IntAct

3 interactions, top by confidence:

A	B	Type	Score
AGAP5	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): AGAP5 (Two-hybrid), AGAP5 (Affinity Capture-MS), AGAP5 (Affinity Capture-MS), AGAP5 (Negative Genetic), AGAP5 (Negative Genetic)

ESM2 similar proteins: A0A1L8F1M4, A0A8M9QN10, A0JMQ9, A6NIR3, A8DZE6, A8WH69, B2KF05, F1QCY8, O43147, O43900, O54880, P0C6P5, P59729, P97433, Q13009, Q18PD9, Q2NKQ1, Q32L09, Q3U5C7, Q58D79, Q5EB20, Q5PQS0, Q5U464, Q60592, Q6IVY4, Q6P0Q8, Q6ZQF7, Q6ZUJ8, Q71QF9, Q768S4, Q7T2V3, Q7TNN8, Q7TSI1, Q7ZVP1, Q803A0, Q80U12, Q80VL3, Q80Y24, Q8BPQ7, Q8BRB7

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

927 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73676769:CT:C	acceptor_gain	1.0000
10:73676771:C:CC	acceptor_gain	1.0000
10:73680067:TCAC:T	donor_loss	1.0000
10:73680068:CACCT:C	donor_loss	1.0000
10:73680069:A:C	donor_loss	1.0000
10:73680070:C:CG	donor_loss	1.0000
10:73680103:CACA:C	acceptor_gain	1.0000
10:73680105:CA:C	acceptor_gain	1.0000
10:73680107:C:CC	acceptor_gain	1.0000
10:73682692:A:AC	donor_gain	1.0000
10:73682693:C:CC	donor_gain	1.0000
10:73682793:ACC:A	acceptor_loss	1.0000
10:73682794:CCT:C	acceptor_loss	1.0000
10:73682796:T:A	acceptor_loss	1.0000
10:73692078:C:CC	acceptor_gain	1.0000
10:73694735:CCAT:C	donor_gain	1.0000
10:73694803:AG:A	acceptor_gain	1.0000
10:73694803:AGC:A	acceptor_loss	1.0000
10:73694804:GCTA:G	acceptor_loss	1.0000
10:73694805:C:CC	acceptor_gain	1.0000
10:73694805:C:T	acceptor_loss	1.0000
10:73694809:A:AC	acceptor_gain	1.0000
10:73694809:A:C	acceptor_gain	1.0000
10:73694812:CA:C	acceptor_gain	1.0000
10:73694813:A:AC	acceptor_gain	1.0000
10:73694813:A:C	acceptor_gain	1.0000
10:73697528:CTTA:C	donor_loss	1.0000
10:73697529:TTACC:T	donor_loss	1.0000
10:73697530:TA:T	donor_loss	1.0000
10:73697531:ACCT:A	donor_loss	1.0000

AlphaMissense

4546 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73675391:A:C	F423L	0.957
10:73675391:A:T	F423L	0.957
10:73675393:A:G	F423L	0.957
10:73675746:A:T	V305D	0.936
10:73674669:G:T	A664D	0.925
10:73674932:A:C	F576L	0.914
10:73674932:A:T	F576L	0.914
10:73674934:A:G	F576L	0.914
10:73675427:A:C	F411L	0.914
10:73675427:A:T	F411L	0.914
10:73675429:A:G	F411L	0.914
10:73675787:C:A	K291N	0.913
10:73675787:C:G	K291N	0.913
10:73674766:A:G	C632R	0.912
10:73675360:A:G	W434R	0.912
10:73675360:A:T	W434R	0.912
10:73674777:A:T	L628H	0.903
10:73675805:T:A	K285N	0.903
10:73675805:T:G	K285N	0.903
10:73675392:A:G	F423S	0.900
10:73675358:C:A	W434C	0.894
10:73675358:C:G	W434C	0.894
10:73675399:A:G	W421R	0.883
10:73675399:A:T	W421R	0.883
10:73674764:G:C	C632W	0.881
10:73674950:T:A	K570N	0.868
10:73674950:T:G	K570N	0.868
10:73675428:A:G	F411S	0.860
10:73674670:C:G	A664P	0.844
10:73674681:G:T	A660E	0.837

dbSNP variants (sampled 300 via entrez): RS1000104499 (10:73699673 C>T), RS1000346048 (10:73688046 TCTAA>T), RS1000570137 (10:73678366 T>C), RS1000581646 (10:73677788 T>G), RS1000837625 (10:73687778 C>T), RS1001004661 (10:73687204 C>A), RS1001187063 (10:73688444 T>G), RS1001279906 (10:73695076 A>T), RS1001289589 (10:73694573 A>C,G), RS1001341932 (10:73694134 A>C), RS1001782497 (10:73676649 G>A,T), RS1002009993 (10:73679877 A>G), RS1002117938 (10:73679388 T>C,G), RS1002946712 (10:73689144 G>A), RS1003015082 (10:73696692 C>A)

Disease associations

OMIM: gene MIM:621156 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005023_14	Initial pursuit acceleration	9.000000e-06
GCST006414_1	Atrial fibrillation	9.000000e-35
GCST007267_52	Systolic blood pressure	4.000000e-13
GCST007269_188	Pulse pressure	2.000000e-09
GCST007656_13	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	2.000000e-10
GCST009541_9	Heart failure	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008434	initial pursuit acceleration
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement

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
Cadmium	decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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