GAPVD1

Summary

GAPVD1 (GTPase activating protein and VPS9 domains 1, HGNC:23375) is a protein-coding gene on chromosome 9q33.3, encoding GTPase-activating protein and VPS9 domain-containing protein 1 (Q14C86). Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking.

Enables GTPase activating protein binding activity and guanyl-nucleotide exchange factor activity. Involved in regulation of protein transport. Located in cytosol and plasma membrane.

Source: NCBI Gene 26130 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial idiopathic steroid-resistant nephrotic syndrome (Supportive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 89 total
• Phenotypes (HPO): 17
• Druggable target: yes
• MANE Select transcript: NM_001282680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23375
Approved symbol	GAPVD1
Name	GTPase activating protein and VPS9 domains 1
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434C212, KIAA1521
Ensembl gene	ENSG00000165219
Ensembl biotype	protein_coding
OMIM	611714
Entrez	26130

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 31 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000297933, ENST00000312123, ENST00000394083, ENST00000394084, ENST00000394104, ENST00000394105, ENST00000431329, ENST00000436712, ENST00000461379, ENST00000467707, ENST00000467750, ENST00000469498, ENST00000469528, ENST00000470056, ENST00000474637, ENST00000479511, ENST00000495588, ENST00000495955, ENST00000497580, ENST00000888082, ENST00000888083, ENST00000888084, ENST00000888085, ENST00000937667, ENST00000937668, ENST00000937669, ENST00000937670, ENST00000937671, ENST00000937672, ENST00000937673, ENST00000937674, ENST00000937675, ENST00000937676, ENST00000937677, ENST00000937678, ENST00000961757, ENST00000961758, ENST00000961759

RefSeq mRNA: 15 — MANE Select: NM_001282680 NM_001282679, NM_001282680, NM_001282681, NM_001330777, NM_001330778, NM_001354293, NM_001354294, NM_001354295, NM_001354296, NM_001354297, NM_001354298, NM_001354299, NM_001354300, NM_001354301, NM_015635

CCDS: CCDS35138, CCDS65130, CCDS65131, CCDS65132, CCDS83413, CCDS83414, CCDS87689

Canonical transcript exons

ENST00000297933 — 28 exons

Exon	Start	End
ENSE00000806712	125321433	125321562
ENSE00000927060	125307413	125307547
ENSE00000927061	125307691	125307880
ENSE00000983662	125331926	125332060
ENSE00000983669	125305063	125305149
ENSE00001155295	125326416	125326589
ENSE00001155301	125323798	125323923
ENSE00001155310	125312452	125312612
ENSE00001370988	125330078	125330218
ENSE00001517458	125268936	125268984
ENSE00001517493	125295458	125295574
ENSE00001591273	125301983	125302826
ENSE00001732996	125346819	125346941
ENSE00001894404	125362606	125367207
ENSE00002158934	125342219	125342299
ENSE00002186824	125298890	125299106
ENSE00003473272	125359420	125359492
ENSE00003506541	125350713	125350872
ENSE00003513429	125360528	125360725
ENSE00003520596	125332510	125332629
ENSE00003525883	125354654	125354841
ENSE00003561201	125337018	125337095
ENSE00003581382	125337221	125337591
ENSE00003618985	125350295	125350404
ENSE00003632088	125349390	125349519
ENSE00003636183	125355644	125355857
ENSE00003789601	125341177	125341264
ENSE00003891854	125261826	125261959

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 95.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5223 / max 248.4952, expressed in 1815 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98501	27.5223	1815

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	95.23	gold quality
epithelium of bronchus	UBERON:0002031	95.10	gold quality
bronchus	UBERON:0002185	94.92	gold quality
nasal cavity epithelium	UBERON:0005384	93.90	gold quality
amniotic fluid	UBERON:0000173	93.83	gold quality
palpebral conjunctiva	UBERON:0001812	93.65	gold quality
upper leg skin	UBERON:0004262	93.34	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.14	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.91	gold quality
cartilage tissue	UBERON:0002418	92.82	gold quality
oviduct epithelium	UBERON:0004804	92.82	gold quality
visceral pleura	UBERON:0002401	92.77	gold quality
middle temporal gyrus	UBERON:0002771	92.67	gold quality
adrenal tissue	UBERON:0018303	92.55	gold quality
tibia	UBERON:0000979	92.52	gold quality
trabecular bone tissue	UBERON:0002483	92.33	gold quality
eye	UBERON:0000970	92.24	gold quality
skin of hip	UBERON:0001554	92.00	gold quality
epithelium of nasopharynx	UBERON:0001951	92.00	gold quality
pleura	UBERON:0000977	91.97	gold quality
colonic epithelium	UBERON:0000397	91.81	gold quality
medial globus pallidus	UBERON:0002477	91.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.71	gold quality
tonsil	UBERON:0002372	91.60	gold quality
seminal vesicle	UBERON:0000998	91.55	gold quality
esophagus squamous epithelium	UBERON:0006920	91.41	gold quality
parietal pleura	UBERON:0002400	91.40	gold quality
bone marrow cell	CL:0002092	91.39	gold quality
squamous epithelium	UBERON:0006914	91.33	gold quality
cervix squamous epithelium	UBERON:0006922	91.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	237.41
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

151 targeting GAPVD1, 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-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548A-5P	99.94	71.27	3482

Literature-anchored findings (GeneRIF, showing 5)

• EGF-stimulated receptor ubiquitination and trafficking are mediated via GAPex-5: GAPex-5-mediated EGFR ubiquitination is independent of Rab5 activation (PMID:17545148)
• The findings suggest that SPIN90, as an adaptor protein, simultaneously binds inactive Rab5 and Gapex5, thereby altering their spatial proximity and facilitating Rab5 activation. (PMID:31358736)
• CRISPR-mediated gene targeting of CK1delta/epsilon leads to enhanced understanding of their role in endocytosis via phosphoregulation of GAPVD1. (PMID:32321936)
• An interdependence between GAPVD1 gene polymorphism, expression level and response to interferon beta in patients with multiple sclerosis. (PMID:33548618)
• Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation. (PMID:33917494)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gapvd1	ENSDARG00000090183
mus_musculus	Gapvd1	ENSMUSG00000026867
rattus_norvegicus	Gapvd1	ENSRNOG00000017925
drosophila_melanogaster	Gapvd1	FBGN0030286
caenorhabditis_elegans		WBGENE00004377

Paralogs (6): VPS9D1 (ENSG00000075399), RIN3 (ENSG00000100599), RIN2 (ENSG00000132669), RABGEF1 (ENSG00000154710), RIN1 (ENSG00000174791), RINL (ENSG00000187994)

Protein

Protein identifiers

GTPase-activating protein and VPS9 domain-containing protein 1 — Q14C86 (reviewed: Q14C86)

Alternative names: GAPex-5, Rab5-activating protein 6

All UniProt accessions (8): B0QZ65, B4DGD8, C9IZ08, C9IZX9, Q14C86, F8W9S7, H0Y4E7, H0Y7I9

UniProt curated annotations — full annotation on UniProt →

Function. Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the Ras-related protein RAB31 by exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 trafficking. In the absence of insulin, it maintains RAB31 in an active state and promotes a futile cycle between LC2A4/GLUT4 storage vesicles and early endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin stimulation, it is translocated to the plasma membrane, releasing LC2A4/GLUT4 from intracellular storage vesicles. Also involved in EGFR trafficking and degradation, possibly by promoting EGFR ubiquitination and subsequent degradation by the proteasome. Has GEF activity for Rab5 and GAP activity for Ras.

Subunit / interactions. Interacts with TRIP10/CIP4. Interacts with RAB5A. (Microbial infection) Interacts with P.falciparum (strain 3D7) CK1.

Subcellular location. Membrane. Endosome.

Tissue specificity. Expressed in erythrocytes (at protein level).

Similarity. Belongs to the GAPVD1 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q14C86-1	1	yes
Q14C86-2	2
Q14C86-3	3
Q14C86-4	4
Q14C86-5	5
Q14C86-6	6

RefSeq proteins (15): NP_001269608, NP_001269609, NP_001269610, NP_001317706, NP_001317707, NP_001341222, NP_001341223, NP_001341224, NP_001341225, NP_001341226, NP_001341227, NP_001341228, NP_001341229, NP_001341230, NP_056450 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001936	RasGAP_dom	Domain
IPR003123	VPS9	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR037191	VPS9_dom_sf	Homologous_superfamily
IPR041545	DUF5601	Domain
IPR045046	Vps9-like	Family

Pfam: PF00616, PF02204, PF18151

UniProt features (59 total): modified residue 23, sequence conflict 15, compositionally biased region 7, region of interest 5, splice variant 5, domain 2, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14C86-F1	63.17	0.33

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

Post-translational modifications (23): 227, 390, 458, 460, 466, 470, 566, 569, 742, 746, 757, 762, 766, 876, 902, 903, 908, 914, 966, 1019 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 209 (showing top): GGGACCA_MIR133A_MIR133B, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, ATGTTAA_MIR302C, GTGCCTT_MIR506, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, AAAGGGA_MIR204_MIR211, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GOBP_REGULATION_OF_TRANSPORT, GOBP_IMPORT_INTO_CELL, MODULE_277, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (4): endocytosis (GO:0006897), regulation of protein transport (GO:0051223), vesicle-mediated transport (GO:0016192), regulation of GTPase activity (GO:0043087)

GO Molecular Function (6): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), GTPase activating protein binding (GO:0032794), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (5): endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), endocytic vesicle (GO:0030139), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Membrane Trafficking	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
GTPase regulator activity	2
cytoplasmic vesicle	2
cellular anatomical structure	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
protein transport	1
regulation of transport	1
regulation of establishment of protein localization	1
transport	1
cellular process	1
regulation of hydrolase activity	1
GTP binding	1
GDP binding	1
enzyme activator activity	1
GTPase binding	1
protein binding	1
cell adhesion molecule binding	1
binding	1
endomembrane system	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2747 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAPVD1	RAB5A	P20339	887
GAPVD1	ALS2	Q96Q42	799
GAPVD1	EEA1	Q15075	777
GAPVD1	RABEP1	Q15276	731
GAPVD1	CCZ1B	P86790	730
GAPVD1	TRIP10	Q15642	722
GAPVD1	MON1A	Q86VX9	715
GAPVD1	RABIF	P47224	703
GAPVD1	RIN1	Q13671	695
GAPVD1	ANKFY1	Q9P2R3	673
GAPVD1	RAB31	Q13636	669
GAPVD1	TBC1D8B	Q0IIM8	643
GAPVD1	APPL1	Q9UKG1	637
GAPVD1	MON1B	Q7L1V2	628
GAPVD1	RABGEF1	Q9UJ41	572

IntAct

119 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
CSNK1E	MCC	psi-mi:“MI:0914”(association)	0.890
YWHAB	GAPVD1	psi-mi:“MI:0915”(physical association)	0.860
CSNK1E	PER2	psi-mi:“MI:0914”(association)	0.850
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
CSNK1D	PER2	psi-mi:“MI:0914”(association)	0.810
CSNK1D	GAPVD1	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
Sh2d5	BCR	psi-mi:“MI:0914”(association)	0.580
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
GAPVD1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.560
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SPATA46	TYW5	psi-mi:“MI:0914”(association)	0.530
CSNK1E	POTEF	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
TSSK1B	HSPA8	psi-mi:“MI:0914”(association)	0.530

BioGRID (253): GAPVD1 (Affinity Capture-RNA), GAPVD1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), GAPVD1 (Two-hybrid), RASA2 (Co-fractionation), RASA3 (Co-fractionation), RASAL1 (Co-fractionation), YWHAB (Co-fractionation), GAPVD1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS)

ESM2 similar proteins: A0M8S4, A0M8T5, A2RV61, A5D794, D3ZAZ5, D4AEC2, O00750, O35625, O42400, O55007, O70239, P57095, Q07DV1, Q07DX4, Q07DY4, Q07E15, Q07E28, Q09YG9, Q09YK4, Q108T9, Q13009, Q14C86, Q155Q3, Q2IBA2, Q2IBE6, Q2IBF7, Q2QLA2, Q2QLB3, Q2QLF8, Q2VUH7, Q3UMB5, Q58DL5, Q60610, Q6GYP7, Q6GYQ0, Q6INP9, Q6PAR5, Q803Q4, Q80Y83, Q8C115

Diamond homologs: A2RV61, A5D794, A8WVM4, P59729, Q10NQ3, Q14C86, Q6PAR5, Q8TB24, Q9GYH7, Q9LT31, Q29HW3, Q9UJ41, Q9VZ08, P97680, Q13671, Q6ZS11, Q80UW3, Q8WYP3, Q921Q7, Q9D684, O18973, O74396, P54787, Q9JM13

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	6	54.4×	1e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	48.0×	2e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	48.0×	2e-07
Activation of BH3-only proteins	6	35.5×	1e-06
RHO GTPases activate PKNs	6	22.7×	1e-05
Intrinsic Pathway for Apoptosis	6	20.9×	2e-05
G2/M Checkpoints	10	16.0×	1e-07
Centrosome maturation	5	15.1×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	9	8.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	31
Benign	18

Top pathogenic / likely-pathogenic (0)

SpliceAI

5145 predictions. Top by Δscore:

Variant	Effect	Δscore
9:125261960:G:GG	donor_gain	1.0000
9:125261960:GTG:G	donor_loss	1.0000
9:125261961:T:A	donor_loss	1.0000
9:125263541:T:TA	acceptor_gain	1.0000
9:125298882:A:AG	acceptor_gain	1.0000
9:125298885:CTTA:C	acceptor_loss	1.0000
9:125298886:TTA:T	acceptor_loss	1.0000
9:125298888:A:AG	acceptor_gain	1.0000
9:125298888:AGT:A	acceptor_gain	1.0000
9:125298889:G:GG	acceptor_gain	1.0000
9:125298889:G:T	acceptor_loss	1.0000
9:125298889:GT:G	acceptor_gain	1.0000
9:125298889:GTG:G	acceptor_gain	1.0000
9:125299105:AGGT:A	donor_loss	1.0000
9:125299106:GG:G	donor_loss	1.0000
9:125299107:GT:G	donor_loss	1.0000
9:125301981:A:AG	acceptor_gain	1.0000
9:125301982:G:GG	acceptor_gain	1.0000
9:125301982:GT:G	acceptor_gain	1.0000
9:125302800:G:GT	donor_gain	1.0000
9:125302824:CAGG:C	donor_loss	1.0000
9:125302825:AGGT:A	donor_loss	1.0000
9:125302827:GT:G	donor_loss	1.0000
9:125302828:T:A	donor_loss	1.0000
9:125305137:A:T	donor_gain	1.0000
9:125305147:AAAG:A	donor_loss	1.0000
9:125305148:AA:A	donor_gain	1.0000
9:125305148:AAG:A	donor_loss	1.0000
9:125305149:AGTA:A	donor_loss	1.0000
9:125305150:G:GG	donor_gain	1.0000

AlphaMissense

9621 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:125298959:T:C	L13P	1.000
9:125299057:T:A	W46R	1.000
9:125299057:T:C	W46R	1.000
9:125299094:T:C	L58P	1.000
9:125302050:G:T	G85W	1.000
9:125302129:C:A	A111D	1.000
9:125302230:G:C	D145H	1.000
9:125302231:A:T	D145V	1.000
9:125302279:T:C	L161P	1.000
9:125302384:T:C	L196P	1.000
9:125302417:T:C	L207P	1.000
9:125302420:T:C	L208P	1.000
9:125302570:T:C	L258P	1.000
9:125302603:T:C	L269P	1.000
9:125302641:T:A	W282R	1.000
9:125302641:T:C	W282R	1.000
9:125302723:T:C	L309P	1.000
9:125302777:T:A	I327K	1.000
9:125302817:T:A	N340K	1.000
9:125302817:T:G	N340K	1.000
9:125302819:T:C	L341P	1.000
9:125307537:T:C	L414P	1.000
9:125326454:T:C	F633L	1.000
9:125326455:T:C	F633S	1.000
9:125326455:T:G	F633C	1.000
9:125326456:T:A	F633L	1.000
9:125326456:T:G	F633L	1.000
9:125326511:A:C	S652R	1.000
9:125326513:T:A	S652R	1.000
9:125326513:T:G	S652R	1.000

dbSNP variants (sampled 300 via entrez): RS1000002956 (9:125290030 T>C), RS1000052618 (9:125274384 T>C), RS1000054595 (9:125349842 G>A), RS1000067452 (9:125295370 T>G), RS1000081800 (9:125343899 T>G), RS1000093201 (9:125367453 G>A), RS1000094697 (9:125340535 A>G), RS1000134077 (9:125338737 A>G,T), RS1000153184 (9:125323710 T>C), RS1000175800 (9:125343683 T>A,C), RS1000217072 (9:125302102 G>A), RS1000217556 (9:125261308 C>G), RS1000260433 (9:125260938 C>T), RS1000292336 (9:125286114 A>G), RS1000310553 (9:125289010 T>C)

Disease associations

OMIM: gene MIM:611714 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant

Mondo (2): autism spectrum disorder (MONDO:0005258), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000969	Edema
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003774	Stage 5 chronic kidney disease
HP:0011947	Respiratory tract infection
HP:0012579	Minimal change glomerulonephritis
HP:0012622	Chronic kidney disease
HP:0031504	Foamy urine
HP:0100539	Periorbital edema

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004904_48	Body mass index	6.000000e-07
GCST004904_64	Body mass index	6.000000e-10
GCST008810_4	Smoking initiation (ever regular vs never regular)	3.000000e-11
GCST010002_280	Refractive error	1.000000e-13
GCST011703_94	Smoking initiation	9.000000e-09
GCST90000025_428	Appendicular lean mass	2.000000e-21
GCST90002401_493	Platelet distribution width	5.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005670	smoking initiation
EFO:0004980	appendicular lean mass
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067409 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10760397	Efficacy	3	interferon beta-1a;interferon beta-1b	Multiple Sclerosis
rs10819043	Efficacy	3	interferon beta-1a;interferon beta-1b	Multiple Sclerosis
rs2291858	Efficacy	3	interferon beta-1a;interferon beta-1b	Multiple Sclerosis

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2291858	GAPVD1	3	2.50	1	interferon beta-1a;interferon beta-1b
rs10760397	GAPVD1	3	2.50	1	interferon beta-1a;interferon beta-1b
rs10819043	GAPVD1	3	2.50	1	interferon beta-1a;interferon beta-1b

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.13	Kd	7324	nM	CHEMBL3752910
5.13	ED50	7362	nM	CHEMBL3752910
5.03	Kd	9424	nM	CHEMBL5653589
5.02	ED50	9473	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148415: Binding affinity to human GAPVD1 incubated for 45 mins by Kinobead based pull down assay	kd	7.3245	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148415: Binding affinity to human GAPVD1 incubated for 45 mins by Kinobead based pull down assay	kd	9.4240	uM

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects methylation	2
Valproic Acid	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	affects phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol AF	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
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Diethylstilbestrol	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Methotrexate	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651457	Binding	Binding affinity to human GAPVD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder