ZFYVE9

Summary

ZFYVE9 (zinc finger FYVE-type containing 9, HGNC:6775) is a protein-coding gene on chromosome 1p32.3, encoding Zinc finger FYVE domain-containing protein 9 (O95405). Early endosomal protein that functions to recruit SMAD2/SMAD3 to intracellular membranes and to the TGF-beta receptor.

This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9372 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 204 total
• MANE Select transcript: NM_004799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6775
Approved symbol	ZFYVE9
Name	zinc finger FYVE-type containing 9
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	SMADIP, SARA, PPP1R173
Ensembl gene	ENSG00000157077
Ensembl biotype	protein_coding
OMIM	603755
Entrez	9372

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000287727, ENST00000357206, ENST00000361625, ENST00000371591, ENST00000469134, ENST00000886335, ENST00000886336, ENST00000886337, ENST00000886338, ENST00000941736

RefSeq mRNA: 2 — MANE Select: NM_004799 NM_004799, NM_007324

CCDS: CCDS563, CCDS564

Canonical transcript exons

ENST00000287727 — 19 exons

Exon	Start	End
ENSE00001030105	52274464	52274584
ENSE00001030109	52278492	52278614
ENSE00001030112	52281661	52281816
ENSE00001030120	52268463	52268632
ENSE00001030124	52266655	52266831
ENSE00001064551	52293453	52293677
ENSE00001064560	52334688	52334768
ENSE00001140989	52263773	52263872
ENSE00001191763	52340126	52340231
ENSE00001191826	52346060	52346634
ENSE00001191836	52337772	52337934
ENSE00001352195	52344768	52344944
ENSE00001369304	52216369	52216474
ENSE00003660950	52303821	52303925
ENSE00003663494	52295895	52295977
ENSE00003693987	52332768	52332918
ENSE00003705899	52233171	52233276
ENSE00003709757	52237488	52239595
ENSE00003718561	52142089	52142403

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 92.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9074 / max 128.1839, expressed in 1636 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2869	13.7988	1634
2866	0.6476	363
2865	0.2469	114
2868	0.1103	44
2867	0.1038	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.23	gold quality
cortical plate	UBERON:0005343	89.38	gold quality
prefrontal cortex	UBERON:0000451	88.70	gold quality
muscle of leg	UBERON:0001383	88.69	gold quality
gastrocnemius	UBERON:0001388	88.52	gold quality
cerebellar cortex	UBERON:0002129	88.09	gold quality
cerebellar hemisphere	UBERON:0002245	88.02	gold quality
tendon	UBERON:0000043	87.71	gold quality
islet of Langerhans	UBERON:0000006	87.29	gold quality
cerebellum	UBERON:0002037	87.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.15	gold quality
medial globus pallidus	UBERON:0002477	87.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.10	gold quality
right frontal lobe	UBERON:0002810	87.02	gold quality
frontal cortex	UBERON:0001870	86.84	gold quality
frontal lobe	UBERON:0016525	86.84	gold quality
neocortex	UBERON:0001950	86.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.53	gold quality
cerebellar vermis	UBERON:0004720	85.45	gold quality
anterior cingulate cortex	UBERON:0009835	85.43	gold quality
cingulate cortex	UBERON:0003027	85.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.33	gold quality
adrenal tissue	UBERON:0018303	85.16	gold quality
skeletal muscle organ	UBERON:0014892	85.04	gold quality
muscle organ	UBERON:0001630	85.03	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.01	gold quality
globus pallidus	UBERON:0001875	84.92	gold quality
cerebral cortex	UBERON:0000956	84.57	gold quality
ganglionic eminence	UBERON:0004023	84.56	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting ZFYVE9, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3609	99.52	69.89	2587

Literature-anchored findings (GeneRIF, showing 18)

• Expression of a SARA mutant protein lacking the FYVE finger inhibits downstream activin A signaling in endothelial cells. (PMID:11877415)
• role in rab5 mediated endocytosis (PMID:12432064)
• SARA MH2 domains function in TGF-beta signaling (PMID:15231848)
• internalization is important for transforming growth factor beta1-induced Smad2 association with Smad anchor for receptor activation (SARA) and Smad2-dependent signaling in human mesangial cells (PMID:15613484)
• SARA acts as a Smad anchor for receptor activation in BMP signaling. (PMID:17356069)
• Protein-protein and protein-lipid interactions organized by SARA regulate the vesicular targeting of rhodopsin-bearing axonemal vesicles to nascent discs at the base of the rod outer segment. (PMID:17693260)
• SARA has a role in regulating cell phenotype and its effects are mediated through modification of the balance between Smad2 and Smad3 signaling (PMID:19620243)
• After stimulation with glucose, expression of SARA decreased in a time-dependent manner in epithelium to mesenchymal transition of proximal tubule cells. (PMID:21200089)
• SARA binds to ERBIN using a new domain, which we have called the ERBID (ERBIN-binding domain) (PMID:21878490)
• no correlation between SARA expression and the levels of TGF-beta1-induced phosphorylation of Smads in various B-cell lymphomas (PMID:22819827)
• TGF-beta1 can induce epithelial-to-mesenchymal transition through reduction in SARA expression, SARA is also basally regulated by its interaction with PI3K. (PMID:22942286)
• The negative influence that perturbation of RNF11 and SARA levels exerts on the lysosomal degradation of EGFRs could underscore the significance of overexpression of RNF11 in certain cancers. (PMID:23222715)
• PI3K-C2a was also required for TGFb receptor-mediated formation of SARA-Smad2/3 complex (PMID:25614622)
• SARA may serve as a potential novel target in pre-Epithelial-mesenchymal transition states for the amelioration renal fibrosis seen in chronic kidney diseases (PMID:26159183)
• we have identified endofin as an important signalling component required for basal and BMP-induced hepcidin expression. (PMID:26358513)
• SARA expression was significantly upregulated in the temporal cortex of patients with temporal lobe epilepsy. (PMID:30847724)
• SMURF2 and SMAD7 induce SARA degradation via the proteasome. (PMID:32283253)
• Longitudinal changes of SARA scale in Friedreich ataxia: Strong influence of baseline score and age at onset. (PMID:37641437)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfyve9b	ENSDARG00000100764
danio_rerio	zfyve9a	ENSDARG00000101903
mus_musculus	Zfyve9	ENSMUSG00000034557
rattus_norvegicus	Zfyve9	ENSRNOG00000027183
drosophila_melanogaster	Sara	FBGN0026369

Protein

Protein identifiers

Zinc finger FYVE domain-containing protein 9 — O95405 (reviewed: O95405)

Alternative names: Mothers against decapentaplegic homolog-interacting protein, Novel serine protease, Receptor activation anchor, Smad anchor for receptor activation

All UniProt accessions (1): O95405

UniProt curated annotations — full annotation on UniProt →

Function. Early endosomal protein that functions to recruit SMAD2/SMAD3 to intracellular membranes and to the TGF-beta receptor. Plays a significant role in TGF-mediated signaling by regulating the subcellular location of SMAD2 and SMAD3 and modulating the transcriptional activity of the SMAD3/SMAD4 complex. Possibly associated with TGF-beta receptor internalization.

Subunit / interactions. Interacts (via the SBD region) with SMAD2; the interaction recruits SMAD2 to the TGF-beta receptor and is disrupted by phosphorylation of SMAD2 upon TGF-beta receptor activation. Interacts with SMAD3. Interacts with TGFBR1 and TGFBR2; the interaction recruits SMAD2 to the TGF-beta receptor. Interacts with PML.

Subcellular location. Cytoplasm. Early endosome membrane.

Tissue specificity. Ubiquitous. In the brain found primarily in the cerebrovascular smooth muscle cells and reactive astrocytes.

Domain organisation. The SMAD binding domain (SBD) interacts with the MH2 domains of SMAD2 or SMAD3. The FYVE-type zinc finger is necessary and sufficient for its localization into early endosomes and mediates the association with PI3P.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
O95405-1	1	yes
O95405-2	2
O95405-3	3

RefSeq proteins (2): NP_004790, NP_015563 (=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
IPR024608	SARA-like_SBD	Domain
IPR035438	SARA/endofin	Family
IPR037145	SARA_Smad-bd_sf	Homologous_superfamily

Pfam: PF01363, PF11409, PF11979

UniProt features (86 total): strand 32, helix 17, mutagenesis site 10, binding site 8, splice variant 3, region of interest 3, sequence variant 3, turn 3, compositionally biased region 3, modified residue 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1DEV	X-RAY DIFFRACTION	2.2
5MJY	X-RAY DIFFRACTION	2.25
4BKW	X-RAY DIFFRACTION	2.53
1MK2	X-RAY DIFFRACTION	2.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95405-F1	58.14	0.30

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): 721; 724; 729; 732; 750; 753; 705; 708

Post-translational modifications (2): 306, 668

Mutagenesis-validated functional residues (10):

Position	Phenotype
782	diminishes complex formation with smad2.
783	diminishes complex formation with smad2.
788	diminishes complex formation with smad2.
790	no effect on complex formation with smad2.
793	no effect on complex formation with smad2.
805	diminishes complex formation with smad2.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2173788	Downregulation of TGF-beta receptor signaling
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-3304356	SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-3656532	TGFBR1 KD Mutants in Cancer

MSigDB gene sets: 153 (showing top): REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, MYOGENIN_Q6, TGCACTT_MIR519C_MIR519B_MIR519A, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, FOXO4_01, CTATGCA_MIR153, CEBPB_01, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, TGANTCA_AP1_C, NKX22_01, GOBP_RESPONSE_TO_GROWTH_FACTOR, DOUGLAS_BMI1_TARGETS_UP, CREBP1_01

GO Biological Process (3): endocytosis (GO:0006897), transforming growth factor beta receptor signaling pathway (GO:0007179), endosomal transport (GO:0016197)

GO Molecular Function (5): 1-phosphatidylinositol binding (GO:0005545), zinc ion binding (GO:0008270), protein domain specific binding (GO:0019904), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): early endosome (GO:0005769), cytosol (GO:0005829), early endosome membrane (GO:0031901), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
TGF-beta receptor signaling activates SMADs	1
Signaling by TGF-beta Receptor Complex	1
Loss of Function of SMAD2/3 in Cancer	1
Loss of Function of TGFBR1 in Cancer	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
vesicle-mediated transport	2
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
intracellular transport	1
phospholipid binding	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
endosome	1
cytoplasm	1
early endosome	1
endosome membrane	1
cellular_component	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFYVE9	SMAD2	Q15796	996
ZFYVE9	SMAD3	P84022	994
ZFYVE9	ERBIN	Q96RT1	827
ZFYVE9	TGFBR2	P37173	825
ZFYVE9	SMAD4	Q13485	797
ZFYVE9	TGFBR1	P36897	755
ZFYVE9	SMAD1	Q15797	700
ZFYVE9	SKIL	P12756	660
ZFYVE9	TMPRSS4	Q9NRS4	632
ZFYVE9	SMAD7	O15105	567
ZFYVE9	CTRB2	Q6GPI1	555
ZFYVE9	CTRB1	P17538	536
ZFYVE9	TENT5A	Q96IP4	520
ZFYVE9	SMURF2	Q9HAU4	518
ZFYVE9	RAB5A	P20339	510

IntAct

93 interactions, top by confidence:

A	B	Type	Score
PPP1CC	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.850
ZFYVE9	PPP1CC	psi-mi:“MI:0915”(physical association)	0.850
ZFYVE9	SMAD2	psi-mi:“MI:0407”(direct interaction)	0.830
ZFYVE9	SMAD2	psi-mi:“MI:0915”(physical association)	0.830
ZFYVE9	SMAD2	psi-mi:“MI:0403”(colocalization)	0.830
SMAD2	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.830
SMAD3	ZFYVE9	psi-mi:“MI:0407”(direct interaction)	0.820
ZFYVE9	SMAD3	psi-mi:“MI:0915”(physical association)	0.820
SMAD3	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.820
SMAD3	ZFYVE9	psi-mi:“MI:0914”(association)	0.820
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
ZFYVE9	PPP1CA	psi-mi:“MI:0915”(physical association)	0.670
PPP1CA	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.670
ZFYVE9	STX3	psi-mi:“MI:0403”(colocalization)	0.570
STX3	ZFYVE9	psi-mi:“MI:0407”(direct interaction)	0.570
STX3	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.570
SMAD2	SMAD9	psi-mi:“MI:0914”(association)	0.550
RHO	ZFYVE9	psi-mi:“MI:0407”(direct interaction)	0.540
ZFYVE9	RHO	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (160): ZFYVE9 (Two-hybrid), RNF11 (Two-hybrid), ZFYVE9 (Affinity Capture-Western), ZFYVE9 (Reconstituted Complex), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-Western), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS), ZFYVE9 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LI88, A4D1E1, D3Z987, D3ZUC6, E5FYH0, E5FYH1, E9Q3S4, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, O35923, O54952, O88491, O95405, P38398, P48754, P51587, P97929, Q0VBV7, Q0VGT4, Q2M3C7, Q3V089, Q56UN5, Q5DTT3, Q5F2C3, Q5VWN6, Q61493, Q68DQ2, Q6J6I8, Q6J6I9, Q6J6J0, Q6NSW3, Q6ZP01, Q7TSY8, Q7Z570, Q80U44, Q864S8, Q864U1

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

7 interactions.

A	Effect	B	Mechanism
PML	up-regulates	ZFYVE9	binding
ZFYVE9	“up-regulates activity”	SMAD2	relocalization
ZFYVE9	“up-regulates activity”	SMAD3	relocalization
TGFBR2	“up-regulates activity”	ZFYVE9	binding
TGFBR1	“up-regulates activity”	ZFYVE9	binding
ZFYVE9	“up-regulates activity”	SMAD3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
Downregulation of TGF-beta receptor signaling	5	34.0×	8e-05
RHOB GTPase cycle	6	15.4×	3e-04
Constitutive Signaling by Aberrant PI3K in Cancer	7	14.8×	8e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	8	12.9×	8e-05
PIP3 activates AKT signaling	8	8.9×	3e-04
RHOA GTPase cycle	7	8.7×	1e-03
RAF/MAP kinase cascade	7	7.1×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
SMAD protein signal transduction	5	50.9×	2e-05
embryonic cranial skeleton morphogenesis	5	40.4×	5e-05
peptidyl-tyrosine phosphorylation	6	35.1×	2e-05
ureteric bud development	5	31.6×	1e-04
fibroblast growth factor receptor signaling pathway	5	19.8×	7e-04
protein autophosphorylation	7	14.1×	1e-04
lung development	5	13.8×	2e-03
transforming growth factor beta receptor signaling pathway	6	13.2×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	167
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4455 predictions. Top by Δscore:

Variant	Effect	Δscore
1:52142400:CGAGG:C	donor_loss	1.0000
1:52142404:G:GG	donor_gain	1.0000
1:52142404:GTGA:G	donor_loss	1.0000
1:52142405:T:G	donor_loss	1.0000
1:52216364:TTTA:T	acceptor_loss	1.0000
1:52216365:TTA:T	acceptor_loss	1.0000
1:52216366:TA:T	acceptor_loss	1.0000
1:52216367:A:AC	acceptor_loss	1.0000
1:52216367:A:AG	acceptor_gain	1.0000
1:52216367:AG:A	acceptor_gain	1.0000
1:52216368:G:GG	acceptor_gain	1.0000
1:52216368:GG:G	acceptor_gain	1.0000
1:52216368:GGATC:G	acceptor_gain	1.0000
1:52216471:AAAG:A	donor_loss	1.0000
1:52216472:AAG:A	donor_loss	1.0000
1:52233168:TAG:T	acceptor_loss	1.0000
1:52233169:A:AG	acceptor_gain	1.0000
1:52233169:A:C	acceptor_loss	1.0000
1:52233169:AG:A	acceptor_gain	1.0000
1:52233170:G:GG	acceptor_gain	1.0000
1:52233170:GG:G	acceptor_gain	1.0000
1:52233273:GAAG:G	donor_gain	1.0000
1:52233277:G:GG	donor_gain	1.0000
1:52233278:T:G	donor_loss	1.0000
1:52268451:T:A	acceptor_gain	1.0000
1:52268452:G:A	acceptor_gain	1.0000
1:52268460:AAGT:A	acceptor_gain	1.0000
1:52268460:AAGTG:A	acceptor_gain	1.0000
1:52268461:A:G	acceptor_gain	1.0000
1:52268630:GAG:G	donor_gain	1.0000

AlphaMissense

9489 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:52239498:C:A	P694Q	1.000
1:52239498:C:G	P694R	1.000
1:52239503:T:A	W696R	1.000
1:52239503:T:C	W696R	1.000
1:52239504:G:C	W696S	1.000
1:52239505:G:C	W696C	1.000
1:52239505:G:T	W696C	1.000
1:52239512:G:C	D699H	1.000
1:52239512:G:T	D699Y	1.000
1:52239513:A:C	D699A	1.000
1:52239513:A:G	D699G	1.000
1:52239513:A:T	D699V	1.000
1:52239530:T:A	C705S	1.000
1:52239530:T:C	C705R	1.000
1:52239531:G:A	C705Y	1.000
1:52239531:G:C	C705S	1.000
1:52239531:G:T	C705F	1.000
1:52239532:C:G	C705W	1.000
1:52239539:T:A	C708S	1.000
1:52239539:T:C	C708R	1.000
1:52239540:G:A	C708Y	1.000
1:52239540:G:C	C708S	1.000
1:52239540:G:T	C708F	1.000
1:52239541:T:G	C708W	1.000
1:52239551:T:A	F712I	1.000
1:52239551:T:C	F712L	1.000
1:52239551:T:G	F712V	1.000
1:52239552:T:C	F712S	1.000
1:52239552:T:G	F712C	1.000
1:52239553:T:A	F712L	1.000

dbSNP variants (sampled 300 via entrez): RS1000018335 (1:52295168 C>T), RS1000023477 (1:52170087 T>A,G), RS1000034835 (1:52300960 A>G), RS1000042895 (1:52342998 C>T), RS1000046692 (1:52173113 A>G), RS1000074078 (1:52342663 G>A), RS1000077902 (1:52172665 C>T), RS1000135802 (1:52276564 G>A,T), RS1000137680 (1:52197679 T>C), RS1000146390 (1:52300845 T>C), RS1000174935 (1:52206082 A>G), RS1000176305 (1:52326367 G>T), RS1000214893 (1:52198023 A>G), RS1000261314 (1:52246681 G>A), RS1000264867 (1:52300407 T>C,G)

Disease associations

OMIM: gene MIM:603755 | 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
GCST90020028_530	Hip circumference adjusted for BMI	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation, affects cotreatment	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression, increases abundance	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8DJ	Ubigene A-549 ZFYVE9 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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