ZFYVE16

Summary

ZFYVE16 (zinc finger FYVE-type containing 16, HGNC:20756) is a protein-coding gene on chromosome 5q14.1, encoding Zinc finger FYVE domain-containing protein 16 (Q7Z3T8). May be involved in regulating membrane trafficking in the endosomal pathway.

This gene encodes an endosomal protein that belongs to the FYVE zinc finger family of proteins. The encoded protein is thought to regulate membrane trafficking in the endosome. This protein functions as a scaffold protein in the transforming growth factor-beta signaling pathway and is involved in positive and negative feedback regulation of the bone morphogenetic protein signaling pathway. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 9765 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 235 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001284236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20756
Approved symbol	ZFYVE16
Name	zinc finger FYVE-type containing 16
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0305, PPP1R69
Ensembl gene	ENSG00000039319
Ensembl biotype	protein_coding
OMIM	608880
Entrez	9765

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 12 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000338008, ENST00000505560, ENST00000507548, ENST00000509558, ENST00000509562, ENST00000510158, ENST00000510995, ENST00000511050, ENST00000511829, ENST00000512442, ENST00000512558, ENST00000512907, ENST00000513789, ENST00000868097, ENST00000868098, ENST00000868099, ENST00000967667, ENST00000967668, ENST00000967669, ENST00000967670, ENST00000967671

RefSeq mRNA: 5 — MANE Select: NM_001284236 NM_001105251, NM_001284236, NM_001284237, NM_001349434, NM_014733

CCDS: CCDS4050

Canonical transcript exons

ENST00000505560 — 19 exons

Exon	Start	End
ENSE00001128768	80408064	80408153
ENSE00002037360	80427492	80427545
ENSE00002048964	80477219	80483379
ENSE00003458251	80472761	80472923
ENSE00003463401	80449591	80449713
ENSE00003470326	80451485	80451709
ENSE00003488924	80456945	80457092
ENSE00003491883	80474663	80474830
ENSE00003515779	80445263	80445405
ENSE00003540522	80443123	80443284
ENSE00003543614	80439936	80440032
ENSE00003555086	80434109	80434217
ENSE00003592307	80456461	80456565
ENSE00003612843	80450431	80450586
ENSE00003613622	80448026	80448404
ENSE00003648120	80436756	80439007
ENSE00003672256	80473754	80473859
ENSE00003678777	80455692	80455774
ENSE00003692549	80459414	80459494

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.1055 / max 868.3864, expressed in 1787 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57304	16.1698	1739
57305	8.8382	1326
57302	2.6178	1301
57300	1.1209	308
57306	0.2138	46
57301	0.1450	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.74	gold quality
endothelial cell	CL:0000115	97.93	gold quality
inferior vagus X ganglion	UBERON:0005363	97.33	gold quality
subthalamic nucleus	UBERON:0001906	97.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.18	gold quality
inferior olivary complex	UBERON:0002127	96.03	gold quality
medulla oblongata	UBERON:0001896	96.02	gold quality
adrenal tissue	UBERON:0018303	95.73	gold quality
superior vestibular nucleus	UBERON:0007227	95.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.45	gold quality
tibia	UBERON:0000979	95.42	gold quality
lateral globus pallidus	UBERON:0002476	95.39	gold quality
spinal cord	UBERON:0002240	95.03	gold quality
ventral tegmental area	UBERON:0002691	94.36	gold quality
calcaneal tendon	UBERON:0003701	94.32	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.06	gold quality
substantia nigra pars compacta	UBERON:0001965	94.00	gold quality
visceral pleura	UBERON:0002401	93.83	gold quality
choroid plexus epithelium	UBERON:0003911	93.67	gold quality
endometrium	UBERON:0001295	93.13	gold quality
primary visual cortex	UBERON:0002436	93.13	gold quality
pigmented layer of retina	UBERON:0001782	92.97	gold quality
periodontal ligament	UBERON:0008266	92.91	gold quality
occipital lobe	UBERON:0002021	92.88	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.63	gold quality
midbrain	UBERON:0001891	92.58	gold quality
stromal cell of endometrium	CL:0002255	92.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.40	gold quality
endocervix	UBERON:0000458	92.36	gold quality
substantia nigra	UBERON:0002038	92.27	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.17
E-GEOD-75367	no	307.63
E-GEOD-70580	no	294.02
E-MTAB-7303	no	88.22
E-GEOD-83139	no	2.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

143 targeting ZFYVE16, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 6)

• marked recruitment of TOM1 to endosomes was observed in cells overexpressing endofin or its carboxyl-terminal fragment (PMID:14613930)
• The key mode of action of Trx-SARA was to reduce the level of Smad2 and Smad3 in complex with Smad4 after TGF-beta1 stimulation. (PMID:16775010)
• Facilitates TGF-beta signaling as a scaffold protein to promote the R-Smad-Smad4 complex formation by bringing Smad4 to the proximity of the receptor complex. (PMID:17272273)
• our study is the first to identify and validate Endofin, DCBLD2, and KIAA0582 as part of a complex EGF phosphotyrosine signaling network (PMID:17570516)
• Disruption of proper localization to the endosomes and the Y515 phosphorylation of Endofin enhanced MAPK activation suggesting that Endofin negatively modulates EGFR signaling following receptor endocytosis. (PMID:19887107)
• Two SNPs located near the ZFYVE16 gene on chromosome 5 may have played a role in the early, multicompartment sacrocolpopexy failure. (PMID:26944198)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekhf1	ENSDARG00000102435
drosophila_melanogaster	CG6051	FBGN0039492
drosophila_melanogaster	CG31064	FBGN0051064
caenorhabditis_elegans		WBGENE00003084

Paralogs (13): RUFY3 (ENSG00000018189), SNX29 (ENSG00000048471), ZFYVE26 (ENSG00000072121), RUNDC3B (ENSG00000105784), RUNDC3A (ENSG00000108309), PLEKHM2 (ENSG00000116786), ZFYVE28 (ENSG00000159733), ZFYVE1 (ENSG00000165861), ZFYVE19 (ENSG00000166140), PLEKHF1 (ENSG00000166289), PLEKHF2 (ENSG00000175895), RUFY1 (ENSG00000176783), RUFY2 (ENSG00000204130)

Protein

Protein identifiers

Zinc finger FYVE domain-containing protein 16 — Q7Z3T8 (reviewed: Q7Z3T8)

Alternative names: Endofin, Endosome-associated FYVE domain protein

All UniProt accessions (5): D6RC80, Q7Z3T8, H0Y8R0, H0YAA4, H0YAB1

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in regulating membrane trafficking in the endosomal pathway. Overexpression induces endosome aggregation. Required to target TOM1 to endosomes.

Subunit / interactions. Interacts (via C-terminus) with TOM1 (via C-terminus); interaction is required to target TOM1 to endosomes. Does not interact with TOM1L1 or TOM1L2.

Subcellular location. Cytoplasm. Early endosome membrane.

Tissue specificity. Widely expressed. Highly expressed in kidney, placenta and lung. Expressed at intermediate level in heart, brain, skeletal muscle, spleen and liver. Weakly expressed in colon, thymus and peripheral blood lymphocytes.

Domain organisation. The FYVE-type zinc finger is necessary and sufficient for its localization into early endosomes and mediates the association with PI3P.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z3T8-1	1	yes
Q7Z3T8-3	2

RefSeq proteins (4): NP_001098721, NP_001271165, NP_001336363, NP_055548 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000306	Znf_FYVE	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017455	Znf_FYVE-rel	Domain
IPR022557	SARA-like_C	Domain
IPR035438	SARA/endofin	Family

Pfam: PF01363, PF11979

UniProt features (52 total): binding site 8, sequence conflict 8, modified residue 7, sequence variant 6, region of interest 4, helix 4, turn 4, strand 3, compositionally biased region 3, splice variant 2, chain 1, zinc finger region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3T7L	X-RAY DIFFRACTION	1.09
5MK0	X-RAY DIFFRACTION	1.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3T8-F1	55.27	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 756; 769; 772; 777; 780; 797; 800; 753

Post-translational modifications (7): 123, 446, 815, 845, 896, 939, 946

Mutagenesis-validated functional residues (1):

Position	Phenotype
753	abolishes localization to endosomes and association with pi3p.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP

MSigDB gene sets: 206 (showing top): GOBP_LYSOSOMAL_TRANSPORT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_PROTEIN_TARGETING, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_LOCALIZATION_TO_LYSOSOME, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_REGULATION_OF_ENDOCYTOSIS, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_VACUOLE

GO Biological Process (5): protein targeting to lysosome (GO:0006622), signal transduction (GO:0007165), vesicle organization (GO:0016050), endosomal transport (GO:0016197), regulation of endocytosis (GO:0030100)

GO Molecular Function (5): 1-phosphatidylinositol binding (GO:0005545), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): early endosome (GO:0005769), cytosol (GO:0005829), early endosome membrane (GO:0031901), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by TGFB family members	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein targeting to vacuole	1
lysosomal transport	1
protein localization to lysosome	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
organelle organization	1
vesicle-mediated transport	1
intracellular transport	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
phospholipid binding	1
anion binding	1
phosphatidylinositol phosphate binding	1
transition metal ion binding	1
binding	1
cation binding	1
endosome	1
cytoplasm	1
early endosome	1
endosome membrane	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

807 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFYVE16	TOM1L2	Q6ZVM7	886
ZFYVE16	TOM1	O60784	884
ZFYVE16	TOM1L1	O75674	876
ZFYVE16	SMAD4	Q13485	634
ZFYVE16	SMAD3	P84022	548
ZFYVE16	FAM151B	Q6UXP7	530
ZFYVE16	SSBP2	P81877	512
ZFYVE16	MSH3	P20585	490
ZFYVE16	SLCO6A1	Q86UG4	490
ZFYVE16	ZNF697	Q5TEC3	476
ZFYVE16	HMGXB4	Q9UGU5	438
ZFYVE16	SMAD2	Q15796	417
ZFYVE16	NUDT3	O95989	406
ZFYVE16	CCNH	P51946	401
ZFYVE16	EGF	P01133	400

IntAct

69 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
ELP3	ELP1	psi-mi:“MI:0914”(association)	0.840
TOM1	ZFYVE16	psi-mi:“MI:0915”(physical association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
ZFYVE16	PPP1CA	psi-mi:“MI:0915”(physical association)	0.660
ZFYVE16	EEA1	psi-mi:“MI:0915”(physical association)	0.540
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
EEA1	IGF2R	psi-mi:“MI:2364”(proximity)	0.450
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
ZFYVE16	SPTAN1	psi-mi:“MI:0915”(physical association)	0.400
RNF11	ZFYVE16	psi-mi:“MI:0915”(physical association)	0.370
Ptpn23	UMAD1	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.350

BioGRID (153): ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Proximity Label-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Proximity Label-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Affinity Capture-MS), ZFYVE16 (Proximity Label-MS), TOM1 (Two-hybrid), ZFYVE16 (Reconstituted Complex), TOM1 (Affinity Capture-Western)

ESM2 similar proteins: A1L2H3, A2AKX3, A5D8S0, B0S6S9, D3Z987, E1BC15, O43303, O60673, O95405, P56715, Q03188, Q2M2Z5, Q3MHH3, Q3V089, Q569L8, Q5BQN8, Q5CZC0, Q5DTT3, Q5R9I1, Q5VWN6, Q61493, Q641I1, Q6NS59, Q6NSW3, Q6ZP01, Q6ZU52, Q7TSH4, Q7Z333, Q7Z3T8, Q80U44, Q80U59, Q86UW6, Q86WS4, Q86XD8, Q8IXS0, Q8MJ03, Q8MJ04, Q8MJ06, Q8N1H7, Q8N7Z5

Diamond homologs: A0A0D1E015, A0JMD2, A1CEK1, A1DFP5, A2QWA2, A4QTV1, A8QCE4, A8XJZ8, B0G126, B0WAQ0, B3MT31, B3P851, B4G2G5, B4IC49, B4JHI7, B4K982, B4M140, B4NFJ7, B4PRU6, D2H5P6, D3ZVP7, D4A8G9, E1BLZ4, F1MM41, F7EP40, O13821, O14964, O59722, O76902, O95405, O96838, P0CS26, P0CS27, P34756, P40343, Q05B78, Q08CN9, Q0CJV3, Q0P4S0, Q0U4Z8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
EPH-ephrin mediated repulsion of cells	5	22.0×	3e-04
Constitutive Signaling by Aberrant PI3K in Cancer	7	17.8×	4e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	13.6×	1e-04
Cargo recognition for clathrin-mediated endocytosis	5	10.5×	6e-03
RAF/MAP kinase cascade	8	9.8×	2e-04
PIP3 activates AKT signaling	7	9.3×	6e-04
Clathrin-mediated endocytosis	5	8.5×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	6	43.6×	3e-06
protein autophosphorylation	5	12.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	191
Likely benign	17
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545111	NM_001284236.3(ZFYVE16):c.3442G>T (p.Asp1148Tyr)	Likely pathogenic

SpliceAI

3133 predictions. Top by Δscore:

Variant	Effect	Δscore
5:80408149:GGGAG:G	donor_gain	1.0000
5:80408150:GGAGG:G	donor_gain	1.0000
5:80408151:GAGGT:G	donor_loss	1.0000
5:80408152:AGGTA:A	donor_loss	1.0000
5:80408153:GGT:G	donor_loss	1.0000
5:80408154:GTAA:G	donor_loss	1.0000
5:80409816:C:G	donor_gain	1.0000
5:80434107:A:AG	acceptor_gain	1.0000
5:80434108:G:GG	acceptor_gain	1.0000
5:80434108:GGC:G	acceptor_gain	1.0000
5:80434213:CCCAG:C	donor_loss	1.0000
5:80434214:CCAGG:C	donor_loss	1.0000
5:80434215:CAGGT:C	donor_loss	1.0000
5:80434216:AG:A	donor_loss	1.0000
5:80434217:GGT:G	donor_loss	1.0000
5:80434218:G:C	donor_loss	1.0000
5:80434219:T:A	donor_loss	1.0000
5:80436752:TCAG:T	acceptor_loss	1.0000
5:80436753:CAGAT:C	acceptor_loss	1.0000
5:80436754:A:AG	acceptor_gain	1.0000
5:80436754:AG:A	acceptor_loss	1.0000
5:80436754:AGAT:A	acceptor_gain	1.0000
5:80436755:G:GG	acceptor_gain	1.0000
5:80436755:GA:G	acceptor_gain	1.0000
5:80436755:GAT:G	acceptor_gain	1.0000
5:80436755:GATG:G	acceptor_gain	1.0000
5:80436755:GATGA:G	acceptor_gain	1.0000
5:80440892:T:TA	acceptor_gain	1.0000
5:80443779:AT:A	acceptor_gain	1.0000
5:80445251:A:AG	acceptor_gain	1.0000

AlphaMissense

10232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:80438915:T:A	W744R	1.000
5:80438915:T:C	W744R	1.000
5:80438917:G:C	W744C	1.000
5:80438917:G:T	W744C	1.000
5:80438942:T:A	C753S	1.000
5:80438942:T:C	C753R	1.000
5:80438943:G:C	C753S	1.000
5:80438944:T:G	C753W	1.000
5:80438963:T:C	F760L	1.000
5:80438964:T:C	F760S	1.000
5:80438965:T:A	F760L	1.000
5:80438965:T:G	F760L	1.000
5:80438984:C:G	H767D	1.000
5:80438987:C:G	H768D	1.000
5:80438990:T:C	C769R	1.000
5:80438991:G:A	C769Y	1.000
5:80438992:C:G	C769W	1.000
5:80440002:T:C	C797R	1.000
5:80440011:T:C	C800R	1.000
5:80438943:G:A	C753Y	0.999
5:80438951:T:A	C756S	0.999
5:80438951:T:C	C756R	0.999
5:80438952:G:C	C756S	0.999
5:80438953:C:G	C756W	0.999
5:80438986:C:A	H767Q	0.999
5:80438986:C:G	H767Q	0.999
5:80438989:T:A	H768Q	0.999
5:80438989:T:G	H768Q	0.999
5:80438990:T:A	C769S	0.999
5:80438991:G:C	C769S	0.999

dbSNP variants (sampled 300 via entrez): RS1000039987 (5:80473027 T>C), RS1000065772 (5:80465155 C>T), RS1000104933 (5:80445748 T>A), RS1000117421 (5:80441449 G>A), RS1000140831 (5:80472470 T>C), RS1000175758 (5:80446189 G>A,C,T), RS1000189455 (5:80478343 A>T), RS1000193420 (5:80472152 T>A,C), RS1000206861 (5:80445987 C>T), RS1000215375 (5:80406093 C>T), RS1000308889 (5:80417486 A>G), RS1000336647 (5:80419389 C>G), RS1000367309 (5:80466107 G>GTT), RS1000389234 (5:80453031 C>T), RS1000390015 (5:80411466 T>C)

Disease associations

OMIM: gene MIM:608880 | disease phenotypes: MIM:108010

GenCC curated gene-disease

Mondo (2): arteriovenous malformations of the brain (MONDO:0007154), dextrocardia (MONDO:0015661)

Orphanet (2): Brain arteriovenous malformation (Orphanet:46724), Dextrocardia (Orphanet:1666)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001651	Dextrocardia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006988_17	Blond vs. brown/black hair color	1.000000e-08
GCST008479_8	Psoriasis	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003914	Dextrocardia	C14.240.400.280; C14.280.400.280; C16.131.240.400.280; C16.131.810.250
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Formaldehyde	decreases expression, increases expression	2
Quercetin	decreases expression, decreases phosphorylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
dicrotophos	decreases expression	1
lead acetate	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
zinc protoporphyrin	decreases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
arsenic disulfide	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Caffeine	affects phosphorylation	1
Clorgyline	increases expression	1
Demecolcine	increases expression	1

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1EF	Abcam HCT 116 ZFYVE16 KO	Cancer cell line	Male
CVCL_D8DI	Ubigene A-549 ZFYVE16 KO	Cancer cell line	Male
CVCL_D8YD	Ubigene HCT 116 ZFYVE16 KO	Cancer cell line	Male
CVCL_D9W1	Ubigene HEK293 ZFYVE16 KO	Transformed cell line	Female
CVCL_E0TB	Ubigene HeLa ZFYVE16 KO	Cancer cell line	Female
CVCL_TZ20	HAP1 ZFYVE16 (-) 1	Cancer cell line	Male
CVCL_TZ21	HAP1 ZFYVE16 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01758211	PHASE3	UNKNOWN	Functional Magnetic Resonance Imagine(fMRI)Navigation in Intracranial Arteriovenous Malformation Surgery
NCT04297033	PHASE2	UNKNOWN	Lovastatin for Treatment of Brain Arteriovenous Malformations
NCT02314377	PHASE1	COMPLETED	Bevacizumab Therapy for Brain Arteriovenous Malformation
NCT01689402	Not specified	COMPLETED	MRI for the Early Evaluation of Acute Intracerebral Hemorrhage
NCT01803685	Not specified	UNKNOWN	Nationwide Treatment Survey of Intracranial Arteriovenous Malformation in China
NCT02085278	Not specified	COMPLETED	Safety of Apollo Micro Catheter in Pediatric Patients
NCT02180958	Not specified	COMPLETED	Evaluation of ONYX in ENDOVASCULAR Treatment of Cerebral AVMs
NCT02602990	Not specified	COMPLETED	Treatment of Cerebral Arteriovenous Malformations With SQUID™ Liquid Embolic Agent
NCT02868008	Not specified	UNKNOWN	Multimodal Imaging Techniques in Assessing the Surgical Risk for Eloquent Arteriovenous Malformations
NCT03209804	Not specified	COMPLETED	Surgical Management of Cerebral Arteriovenous Malformations Within Hybrid Operation Room
NCT03367975	Not specified	UNKNOWN	NIRS Monitoring During Intracranial Interventions
NCT03413852	Not specified	UNKNOWN	Treatment of Cerebral Arteriovenous Malformations With SQUID Liquid Embolic Agent (CHOICE)
NCT03676868	Not specified	RECRUITING	Biology of Cerebral Arteriovenous Malformations and Prognosis of Cerebral Arteriovenous Malformations
NCT03731000	Not specified	RECRUITING	PHIL® Embolic System Pediatric IDE
NCT03995823	Not specified	COMPLETED	Evaluation of Nidus Occlusion After Gamma Knife Radiosurgery of Cerebral Arteriovenous Malformations Using Magnetic Resonance Imaging
NCT04328181	Not specified	UNKNOWN	Comparison of Imaging Quality Between Spectral Photon Counting Computed Tomography (SPCCT) and Dual Energy Computed Tomography (DECT)
NCT04553549	Not specified	COMPLETED	Safety and Feasibility of the Infinity Catheter for Radial Access
NCT04572568	Not specified	RECRUITING	Registry of Multimodality Treatment for Brain Arteriovenous Malformation in Mainland China
NCT04593966	Not specified	UNKNOWN	Pediatric and Adult Cerebral Arteriovenous Malformation Neurofunctional Outcomes
NCT05058482	Not specified	UNKNOWN	Non-adhesive Liquid Embolic System in the Embolization of Cerebral Arteriovenous Malformations
NCT05776706	Not specified	NOT_YET_RECRUITING	Clinical Trial for the Validation of AR Based Neuronavigation System
NCT05933330	Not specified	ACTIVE_NOT_RECRUITING	Hereditary Hemorrhagic Telangiectasia and Neurovascular Manifestations, in the Danish HHT Database
NCT06259292	Not specified	RECRUITING	Comprehensive HHT Outcomes Registry of the United States (CHORUS)
NCT06479343	Not specified	RECRUITING	Efficacy and Safety of the Liquid Embolic System (Tonbridge) for Endovascular Treatment of Cerebrovascular Malformations
NCT07103304	Not specified	NOT_YET_RECRUITING	Liquid Biopsies for Detecting Somatic Mutations in Sporadic Cerebral Arteriovenous Malformations.
NCT07314047	Not specified	RECRUITING	The Liquid Embolic Agent for the Treatment of Brain Arteriovenous Malformation
NCT07353736	Not specified	NOT_YET_RECRUITING	Cerebral Arteriovenous Malformation With Aneurysm: Epidemiology, Clinical Features, and Prognosis