AGAP4

Summary

AGAP4 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 4, HGNC:23459) is a protein-coding gene on chromosome 10q11.22, encoding Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (Q96P64). Putative GTPase-activating protein.

Predicted to enable GTPase activator activity and GTPase activity.

Source: NCBI Gene 119016 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 153 total — 1 likely-pathogenic
• MANE Select transcript: NM_001276343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23459
Approved symbol	AGAP4
Name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 4
Location	10q11.22
Locus type	gene with protein product
Status	Approved
Aliases	Em:AC012044.1, MRIP2
Ensembl gene	ENSG00000188234
Ensembl biotype	protein_coding
OMIM	621155
Entrez	119016

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000430779, ENST00000448048, ENST00000490752, ENST00000495243, ENST00000616763, ENST00000970389

RefSeq mRNA: 4 — MANE Select: NM_001276343 NM_001276343, NM_001393377, NM_001393378, NM_133446

CCDS: CCDS7215, CCDS91238

Canonical transcript exons

ENST00000616763 — 8 exons

Exon	Start	End
ENSE00002469237	45847125	45847500
ENSE00002706827	45825594	45827390
ENSE00002848560	45841653	45841687
ENSE00003512230	45844326	45844394
ENSE00003557616	45834016	45834116
ENSE00003564276	45846687	45846755
ENSE00003645446	45828029	45828080
ENSE00003786965	45831394	45831429

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.10.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	95.10	gold quality
cerebellar hemisphere	UBERON:0002245	95.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.09	gold quality
cerebellum	UBERON:0002037	94.93	gold quality
right uterine tube	UBERON:0001302	92.77	gold quality
pituitary gland	UBERON:0000007	92.66	gold quality
body of pancreas	UBERON:0001150	91.93	gold quality
adenohypophysis	UBERON:0002196	91.87	gold quality
fundus of stomach	UBERON:0001160	91.34	gold quality
right testis	UBERON:0004534	91.28	gold quality
left testis	UBERON:0004533	91.08	gold quality
right frontal lobe	UBERON:0002810	90.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.90	gold quality
endometrium	UBERON:0001295	90.88	gold quality
right lobe of thyroid gland	UBERON:0001119	90.76	gold quality
left lobe of thyroid gland	UBERON:0001120	90.69	gold quality
testis	UBERON:0000473	90.51	gold quality
thyroid gland	UBERON:0002046	90.51	gold quality
left ovary	UBERON:0002119	90.47	gold quality
primary visual cortex	UBERON:0002436	90.47	gold quality
right ovary	UBERON:0002118	90.44	gold quality
superior frontal gyrus	UBERON:0002661	90.43	gold quality
metanephros cortex	UBERON:0010533	90.25	gold quality
spleen	UBERON:0002106	90.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.06	gold quality
endocervix	UBERON:0000458	89.87	gold quality
right lobe of liver	UBERON:0001114	89.72	gold quality
small intestine	UBERON:0002108	89.72	gold quality
prostate gland	UBERON:0002367	89.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting AGAP4, 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-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-8080	99.82	67.52	1342
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-212-5P	96.83	67.43	950
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722

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), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 — Q96P64 (reviewed: Q96P64)

Alternative names: Centaurin-gamma-like family member 1, Centaurin-gamma-like family member 5

All UniProt accessions (2): A0A087X0Z1, Q96P64

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 (4): NP_001263272, NP_001380306, NP_001380307, NP_597703 (=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 (17 total): compositionally biased region 5, region of interest 4, domain 2, repeat 2, chain 1, sequence variant 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96P64-F1	63.70	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): GCM_GSPT1, GGGTGGRR_PAX4_03, GCM_NF2, ROSS_AML_WITH_PML_RARA_FUSION, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, ZWANG_DOWN_BY_2ND_EGF_PULSE, GCM_RAB10, GTGCAAA_MIR507, CHAMP1_TARGET_GENES

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

246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGAP4	CCDC183	Q5T5S1	419
AGAP4	PPP1R37	O75864	404
AGAP4	POTEI	P0CG38	403
AGAP4	POTEJ	P0CG39	400
AGAP4	AADACL3	Q5VUY0	399
AGAP4	ARID3C	A6NKF2	393
AGAP4	ZNF418	Q8TF45	371
AGAP4	CHCHD1	Q96BP2	370
AGAP4	LINGO3	P0C6S8	365
AGAP4	TMEM147	Q9BVK8	357
AGAP4	CPNE2	Q96FN4	354
AGAP4	SAMD14	Q8IZD0	354
AGAP4	NALF1	B1AL88	348
AGAP4	UROC1	Q96N76	321
AGAP4	CUZD1	Q86UP6	312

IntAct

4 interactions, top by confidence:

A	B	Type	Score
AGAP4	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
HSPB1	AGAP4	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): AGAP4 (Two-hybrid), AGAP4 (Affinity Capture-MS), AGAP4 (Affinity Capture-MS), AGAP4 (Negative Genetic), AGAP4 (Negative Genetic), AGAP4 (Affinity Capture-RNA), AGAP4 (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	145
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2498203	NC_000010.11:g.45704708_(49974954_50015268)del	Likely pathogenic

SpliceAI

1092 predictions. Top by Δscore:

Variant	Effect	Δscore
10:45828024:CTTA:C	donor_loss	1.0000
10:45828026:TACC:T	donor_loss	1.0000
10:45828027:ACCGC:A	donor_loss	1.0000
10:45828028:C:CG	donor_loss	1.0000
10:45828079:CT:C	acceptor_gain	1.0000
10:45828081:C:CC	acceptor_gain	1.0000
10:45831389:CTCA:C	donor_loss	1.0000
10:45831390:TCA:T	donor_loss	1.0000
10:45831391:CACCT:C	donor_loss	1.0000
10:45831392:A:C	donor_loss	1.0000
10:45831430:C:CC	acceptor_gain	1.0000
10:45834014:A:AC	donor_gain	1.0000
10:45834015:C:CC	donor_gain	1.0000
10:45834015:CGAT:C	donor_gain	1.0000
10:45834015:CGATA:C	donor_gain	1.0000
10:45834115:ACCT:A	acceptor_loss	1.0000
10:45834116:CCTGA:C	acceptor_loss	1.0000
10:45834117:C:CG	acceptor_loss	1.0000
10:45841688:C:CC	acceptor_gain	1.0000
10:45844325:CCAT:C	donor_gain	1.0000
10:45844395:C:CC	acceptor_gain	1.0000
10:45844399:A:C	acceptor_gain	1.0000
10:45844402:C:CT	acceptor_gain	1.0000
10:45844403:A:AC	acceptor_gain	1.0000
10:45844403:A:C	acceptor_gain	1.0000
10:45846686:CCAT:C	donor_gain	1.0000
10:45827387:AAACC:A	acceptor_loss	0.9900
10:45827390:CC:C	acceptor_loss	0.9900
10:45827391:C:CA	acceptor_loss	0.9900
10:45827392:T:C	acceptor_loss	0.9900

AlphaMissense

4549 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:45826266:T:A	K547N	0.973
10:45826266:T:G	K547N	0.973
10:45826248:A:C	F553L	0.950
10:45826248:A:T	F553L	0.950
10:45826250:A:G	F553L	0.950
10:45826707:A:C	F400L	0.949
10:45826707:A:T	F400L	0.949
10:45826709:A:G	F400L	0.949
10:45826267:T:A	K547I	0.936
10:45826676:A:G	W411R	0.934
10:45826676:A:T	W411R	0.934
10:45827062:A:T	V282D	0.934
10:45826278:C:A	W543C	0.928
10:45826278:C:G	W543C	0.928
10:45826280:A:G	W543R	0.925
10:45826280:A:T	W543R	0.925
10:45826743:A:C	F388L	0.925
10:45826743:A:T	F388L	0.925
10:45826745:A:G	F388L	0.925
10:45826684:C:G	R408P	0.924
10:45827103:C:A	K268N	0.917
10:45827103:C:G	K268N	0.917
10:45826744:A:G	F388S	0.914
10:45826509:C:A	W466C	0.910
10:45826509:C:G	W466C	0.910
10:45826268:T:C	K547E	0.909
10:45826674:C:A	W411C	0.909
10:45826674:C:G	W411C	0.909
10:45827121:T:A	K262N	0.908
10:45827121:T:G	K262N	0.908

dbSNP variants (sampled 300 via entrez): RS1045725 (10:45853613 G>C), RS1057791 (10:45855951 A>G), RS111351178 (10:45830503 T>G), RS11239607 (10:45825275 G>A,T), RS11239608 (10:45825390 C>A,T), RS1156229809 (10:45845674 C>A,T), RS1156358389 (10:45853931 T>C), RS1156359855 (10:45844667 A>T), RS1156381232 (10:45827588 T>C,G), RS1156456774 (10:45855453 G>A), RS1156466920 (10:45826721 G>A,T), RS1156473465 (10:45836657 G>A), RS1156532043 (10:45837700 G>C), RS1156620888 (10:45847038 C>T), RS1156633510 (10:45856319 A>G)

Disease associations

OMIM: gene MIM:621155 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000585_14	Mean corpuscular volume	3.000000e-11
GCST000587_14	Mean corpuscular hemoglobin	4.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin

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
Estradiol	affects binding, increases expression	2
bisphenol A	increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
Atrazine	decreases expression	1
Cadmium	decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases expression	1
Vitamin E	decreases expression	1
Levonorgestrel	affects cotreatment, decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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