SYNPO2

Summary

SYNPO2 (synaptopodin 2, HGNC:17732) is a protein-coding gene on chromosome 4q26, encoding Synaptopodin-2 (Q9UMS6). Has an actin-binding and actin-bundling activity.

Enables alpha-actinin binding activity and filamin binding activity. Involved in positive regulation of actin filament bundle assembly; positive regulation of cell migration; and regulation of Rho-dependent protein serine/threonine kinase activity. Located in several cellular components, including Z disc; focal adhesion; and stress fiber.

Source: NCBI Gene 171024 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 200 total
• MANE Select transcript: NM_133477

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17732
Approved symbol	SYNPO2
Name	synaptopodin 2
Location	4q26
Locus type	gene with protein product
Status	Approved
Aliases	MYOPODIN
Ensembl gene	ENSG00000172403
Ensembl biotype	protein_coding
OMIM	620941
Entrez	171024

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000307142, ENST00000429713, ENST00000434046, ENST00000448416, ENST00000504178, ENST00000610556, ENST00000627783

RefSeq mRNA: 7 — MANE Select: NM_133477 NM_001128933, NM_001128934, NM_001286754, NM_001286755, NM_001389263, NM_001389264, NM_133477

CCDS: CCDS34054, CCDS47128, CCDS47129, CCDS75185, CCDS75186, CCDS93613

Canonical transcript exons

ENST00000307142 — 5 exons

Exon	Start	End
ENSE00001177164	119029845	119032027
ENSE00001213846	119023430	119023581
ENSE00001213865	119026627	119027438
ENSE00001482316	119057401	119061247
ENSE00003844283	118888854	118889141

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.6530 / max 2762.1503, expressed in 1101 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49447	6.8973	524
49444	5.6023	369
49431	5.2701	572
49446	3.5037	367
49448	2.5345	351
49433	0.8991	294
49429	0.6525	264
49445	0.3507	96
49434	0.3023	121
49432	0.1472	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.84	gold quality
saphenous vein	UBERON:0007318	99.84	gold quality
seminal vesicle	UBERON:0000998	99.78	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.66	gold quality
nipple	UBERON:0002030	99.65	gold quality
urethra	UBERON:0000057	99.64	gold quality
biceps brachii	UBERON:0001507	99.60	gold quality
body of tongue	UBERON:0011876	99.42	gold quality
superficial temporal artery	UBERON:0001614	99.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.10	gold quality
lower esophagus	UBERON:0013473	99.07	gold quality
pericardium	UBERON:0002407	99.03	gold quality
mucosa of stomach	UBERON:0001199	98.95	gold quality
vena cava	UBERON:0004087	98.94	gold quality
pylorus	UBERON:0001166	98.81	gold quality
gastrocnemius	UBERON:0001388	98.78	gold quality
caput epididymis	UBERON:0004358	98.73	gold quality
popliteal artery	UBERON:0002250	98.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.72	gold quality
tibial artery	UBERON:0007610	98.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.62	gold quality
cardia of stomach	UBERON:0001162	98.61	gold quality
artery	UBERON:0001637	98.55	gold quality
muscle of leg	UBERON:0001383	98.39	gold quality
colonic epithelium	UBERON:0000397	98.35	gold quality
right coronary artery	UBERON:0001625	98.32	gold quality
corpus epididymis	UBERON:0004359	98.32	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.29	gold quality
penis	UBERON:0000989	98.11	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	992.21
E-MTAB-10287	yes	49.61
E-GEOD-135922	yes	35.61
E-MTAB-8410	yes	26.12
E-HCAD-11	yes	20.70
E-CURD-119	yes	13.93
E-MTAB-6678	yes	11.65
E-CURD-46	yes	10.50
E-GEOD-110499	no	886.39
E-GEOD-99795	no	5.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

270 targeting SYNPO2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-302E	99.96	70.74	2669

Literature-anchored findings (GeneRIF, showing 16)

• myopodin functions as a tumor suppressor gene to limit the growth and to inhibit the metastasis of cancer cells (PMID:15111326)
• Imp13 functions in myopodin import and the regulation of this event is critical for normal and abnormal cellular differentiation. (PMID:17828378)
• The myopodin new isoform (Myo2), in addition to the two predicted isoforms (Myo1 and Myo3), are transcribed in various mammalian tumor cell lines. (PMID:18371299)
• The subcellular localization of myopodin is involved in its suppressor or activator function in tumorigenesis. (PMID:19360353)
• the N-terminus of myopodin binds integrin-linked kinase (ILK) both in vivo and in vitro (PMID:21643011)
• myopodin is epigenetically modified in colon cancer (PMID:22252522)
• High Synaptopodin-2 induces assembly of peripheral actin bundles and immature focal adhesions to promote lamellipodia formation and prostate cancer cell migration. (PMID:25883213)
• Promoter hypermethylation and down regulation of SYNPO2 has significance in the prognosis of melanoma patients. (PMID:25918983)
• LMOD1, SYNPO2, PDLIM7, PLN, and SYNM down-regulation reflect the altered phenotype of smooth muscle cells in vascular disease and could be early sensitive markers of SMC dedifferentiation. (PMID:27470516)
• High Myopodin methylation is associated with metastasis in kidney cancer. (PMID:27592258)
• Results show that SYNPO2 gene plays an important role in the etiology of epithelial ovarian cancer, suggesting that this gene may be a potential genetic modifier for developing epithelial ovarian cancer. (PMID:28231729)
• These findings uncover a suppressive role of SYNPO2 in triple-negative breast cancer (TNBC) metastasis via inhibition of YAP/TAZ, and suggest that SYNPO2 might provide a potential prognosis marker and novel therapeutic strategy. (PMID:28991374)
• Synaptopodin-2 promotes hepatocellular carcinoma metastasis via calcineurin-induced nuclear-cytoplasmic translocation. (PMID:32278815)
• SYNPO2 suppresses hypoxia-induced proliferation and migration of colorectal cancer cells by regulating YAP-KLF5 axis. (PMID:34333382)
• SYNPO2 promotes the development of BLCA by upregulating the infiltration of resting mast cells and increasing the resistance to immunotherapy. (PMID:38038167)
• Synaptopodin-2 Isoforms Have Specific Binding Partners and Display Distinct, Muscle Cell Type-Specific Expression Patterns. (PMID:38201288)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	synpo2b	ENSDARG00000077157
mus_musculus	Synpo2	ENSMUSG00000050315
rattus_norvegicus	Synpo2	ENSRNOG00000014867
drosophila_melanogaster	CG1674	FBGN0039897

Paralogs (2): SYNPO2L (ENSG00000166317), SYNPO (ENSG00000171992)

Protein

Protein identifiers

Synaptopodin-2 — Q9UMS6 (reviewed: Q9UMS6)

Alternative names: Genethonin-2, Myopodin

All UniProt accessions (4): B4DLE4, B4E258, Q9UMS6, H0Y9Y3

UniProt curated annotations — full annotation on UniProt →

Function. Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner. At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes. Involved in regulation of cell migration. May be a tumor suppressor. Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia. Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro.

Subunit / interactions. May self-associate in muscle cells under oxidative stress. Binds F-actin. Interacts with ACTN2; ACTN2 is proposed to anchor SYOP2 at Z lines in mature myocytes. Interacts with AKAP6, PPP3CA and CAMK2A. Interacts (phosphorylated form) with YWHAB; YWHAB competes with ACTN2 for interaction with SYNPO2. Interacts with KPNA2; mediating nuclear import of SYNOP2; dependent on interaction with YWHAB. Interacts with IPO13; may be implicated in SYNOP2 nuclear import. Interacts with ZYX, FLNC, ILK. Interacts with BAG3 (via WW 1 domain). May associate with the CASA complex consisting of HSPA8, HSPB8 and BAG3. Interacts with VPS18.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Myofibril. Sarcomere. Z line. Cell junction. Focal adhesion Cytoplasm. Cytoskeleton Cytoplasm.

Tissue specificity. Expressed in heart muscle. Isoform 5 is specifically expressed in skeletal muscle.

Post-translational modifications. Phosphorylated by PKA, and by CaMK2 at multiple sites. Dephosphorylated by calcineurin; abrogating interaction with YWHAB and impairing nuclear import. Phosphorylated by ILK.

Domain organisation. The PPPY motif interacts with the WW domain 1 of BAG3.

Induction. Down-regulated in muscle cell lines derived from patients with Duchenne muscular dystrophy (DMD).

Miscellaneous. Produced by alternative promoter usage. =Produced by alternative splicing of isoform 1. =Produced by alternative splicing of isoform 1. =Produced by alternative splicing of isoform 1. Produced by alternative promoter usage.

Similarity. Belongs to the synaptopodin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9UMS6-1	1, Myo1, SYNOPb, Synop2A	yes
Q9UMS6-2	2, Myo3, SYNOPa, Synop2C
Q9UMS6-3	3, Myo2, SYNOPc, Synop2B
Q9UMS6-4	4, Myo4, Synop2D
Q9UMS6-5	5, (delta)N-MYO1, SYNOPd, SYNOP2As

RefSeq proteins (7): NP_001122405, NP_001122406, NP_001273683, NP_001273684, NP_001376192, NP_001376193, NP_597734* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR051976	Synaptopodin_domain	Family

Pfam: PF00595

UniProt features (76 total): modified residue 26, region of interest 19, compositionally biased region 12, sequence conflict 7, splice variant 4, sequence variant 4, short sequence motif 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMS6-F1	49.86	0.09

Functional residue map

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

Post-translational modifications (26): 274, 310, 329, 330, 333, 548, 549, 551, 604, 610, 611, 622, 626, 705, 729, 755, 774, 777, 781, 902 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 256 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOZGIT_ESR1_TARGETS_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CHANDRAN_METASTASIS_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, WANG_LMO4_TARGETS_DN, GOBP_ACTIN_FILAMENT_ORGANIZATION, WONG_ENDMETRIUM_CANCER_DN

GO Biological Process (3): positive regulation of cell migration (GO:0030335), positive regulation of actin filament bundle assembly (GO:0032233), obsolete regulation of Rho-dependent protein serine/threonine kinase activity (GO:2000298)

GO Molecular Function (6): actin binding (GO:0003779), filamin binding (GO:0031005), muscle alpha-actinin binding (GO:0051371), alpha-actinin binding (GO:0051393), 14-3-3 protein binding (GO:0071889), protein binding (GO:0005515)

GO Cellular Component (11): stress fiber (GO:0001725), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), organelle (GO:0043226), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoskeletal protein binding	2
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of actin filament bundle assembly	1
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
alpha-actinin binding	1
actinin binding	1
protein binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
cell-substrate junction	1
cytoskeleton	1
I band	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

1214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNPO2	FLNC	Q14315	767
SYNPO2	BAG3	O95817	740
SYNPO2	HSPB8	Q9UJY1	695
SYNPO2	MYOT	Q9UBF9	647
SYNPO2	MYOZ1	Q9NP98	639
SYNPO2	FLNB	O75369	617
SYNPO2	FLNA	P21333	605
SYNPO2	PGM5	Q15124	568
SYNPO2	ACTN2	P35609	561
SYNPO2	HSPA4	P34932	544
SYNPO2	PPP3CB	P16298	536
SYNPO2	STUB1	Q9UNE7	530
SYNPO2	ACTN1	P12814	491
SYNPO2	YWHAB	P31946	479
SYNPO2	SQSTM1	Q13501	475

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SYNPO2	ILK	psi-mi:“MI:0915”(physical association)	0.610
ILK	SYNPO2	psi-mi:“MI:0915”(physical association)	0.610
SYNPO2	ILK	psi-mi:“MI:0407”(direct interaction)	0.610
SYNPO2	ILK	psi-mi:“MI:0403”(colocalization)	0.610
NEDD4	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
SYNPO2	CDK6	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ABCC4	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
SYNPO2	ASIC3	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
SYNPO2	FZD7	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
E6	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
ORF putative E6	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
KIR3DL3	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
MAP2K2	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
PBK	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
RALBP1	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
RASSF6	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC15A5	SYNPO2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (34): SYNPO2 (Affinity Capture-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Proximity Label-MS), SYNPO2 (Affinity Capture-RNA), SYNPO2 (Affinity Capture-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Protein-peptide), SYNPO2 (Proximity Label-MS), SYNPO2 (Affinity Capture-MS), SYNPO2 (Protein-peptide)

ESM2 similar proteins: A2APB8, A4IG59, A4IH24, A5A6J4, A6H6Z7, A8K0Z3, B0BM24, B2RYF7, C4AMC7, E2RYF8, E7EXT2, F4I2H7, M0R3K6, O13024, O60566, O95990, P13505, P14317, P49710, Q0IHP2, Q0VBD2, Q2KI00, Q32N93, Q3B820, Q3TGF2, Q5NVP3, Q5RAF2, Q5U4F3, Q5ZKA6, Q62736, Q66KE9, Q68FU8, Q6AY14, Q6DDV8, Q6NUF4, Q6VEQ5, Q6ZQ58, Q78TU8, Q7L590, Q84ZT9

Diamond homologs: A1ZA47, A2ALU4, A5H447, D4A702, E1BKA3, O00151, O14639, O43294, O60711, O70209, O70400, O75112, O94929, P20271, P48059, P49023, P49024, P50464, P52944, Q09476, Q0WSN2, Q13796, Q15942, Q1JQB5, Q2KJ33, Q2TCH4, Q2YDK0, Q3MHZ4, Q3SX26, Q3SX40, Q3SYZ8, Q3T0X8, Q3TJD7, Q55BI0, Q5F464, Q5R7I1, Q5RCF7, Q5TD97, Q5U2Z2, Q5XI07

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ILK	“up-regulates activity”	SYNPO2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	181
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1700 predictions. Top by Δscore:

Variant	Effect	Δscore
4:118888959:C:G	donor_gain	1.0000
4:118889031:G:GT	donor_gain	1.0000
4:118889032:A:T	donor_gain	1.0000
4:119023419:A:AG	acceptor_gain	1.0000
4:119023424:A:AG	acceptor_gain	1.0000
4:119023545:A:T	donor_gain	1.0000
4:119023577:AAAAG:A	donor_loss	1.0000
4:119023582:G:GC	donor_loss	1.0000
4:119023583:T:G	donor_loss	1.0000
4:118953155:GC:G	donor_gain	0.9900
4:119017526:T:TA	donor_gain	0.9900
4:119017527:A:AA	donor_gain	0.9900
4:119023420:C:G	acceptor_gain	0.9900
4:119023425:C:G	acceptor_gain	0.9900
4:119023425:CTCA:C	acceptor_loss	0.9900
4:119023426:TCAG:T	acceptor_loss	0.9900
4:119023427:CA:C	acceptor_loss	0.9900
4:119023428:A:AG	acceptor_gain	0.9900
4:119023429:G:GC	acceptor_gain	0.9900
4:119023429:G:GT	acceptor_loss	0.9900
4:119023429:GA:G	acceptor_gain	0.9900
4:119023429:GATTC:G	acceptor_gain	0.9900
4:119026625:A:AG	acceptor_gain	0.9900
4:119026626:G:GG	acceptor_gain	0.9900
4:119026626:GACC:G	acceptor_gain	0.9900
4:119027435:GCAC:G	donor_gain	0.9900
4:119027439:G:GG	donor_gain	0.9900
4:119029841:CTA:C	acceptor_loss	0.9900
4:119029842:TAG:T	acceptor_loss	0.9900
4:119029843:A:AG	acceptor_gain	0.9900

AlphaMissense

8155 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:119029911:T:A	I379N	0.999
4:119029914:C:A	A380D	0.999
4:119029923:T:C	L383P	0.999
4:119029964:T:C	F397L	0.999
4:119029965:T:C	F397S	0.999
4:119029966:T:A	F397L	0.999
4:119029966:T:G	F397L	0.999
4:119030990:G:A	G739R	0.999
4:119030990:G:C	G739R	0.999
4:119030990:G:T	G739W	0.999
4:119031008:T:C	F745L	0.999
4:119031010:C:A	F745L	0.999
4:119031010:C:G	F745L	0.999
4:119029889:G:C	A372P	0.998
4:119029901:T:C	C376R	0.998
4:119029911:T:G	I379S	0.998
4:119029920:T:C	L382P	0.998
4:119029923:T:A	L383Q	0.998
4:119029952:G:A	G393R	0.998
4:119029952:G:C	G393R	0.998
4:119029965:T:G	F397C	0.998
4:119030991:G:A	G739E	0.998
4:119030993:G:C	A740P	0.998
4:119031007:T:A	N744K	0.998
4:119031007:T:G	N744K	0.998
4:119031009:T:C	F745S	0.998
4:119031705:T:C	F977S	0.998
4:118889085:T:A	W17R	0.997
4:118889085:T:C	W17R	0.997
4:119029895:T:C	S374P	0.997

dbSNP variants (sampled 300 via entrez): RS1000000983 (4:118938551 A>C,T), RS1000008612 (4:118914593 GT>G,GTT), RS1000011219 (4:118873671 T>G), RS1000018217 (4:118894724 G>C), RS1000026019 (4:119048370 A>C), RS1000044333 (4:118979732 C>T), RS1000048163 (4:118975584 A>G), RS1000056006 (4:118869392 T>C), RS1000070021 (4:119048659 C>A), RS1000070470 (4:118998905 G>T), RS1000079136 (4:118887714 G>A), RS10000943 (4:118918154 C>G,T), RS10001115 (4:118860712 A>C), RS1000115306 (4:119018768 T>C), RS1000134731 (4:118952367 CT>C,CTT)

Disease associations

OMIM: gene MIM:620941 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002122_4	IgE levels in asthmatics	8.000000e-06
GCST002337_125	Amyotrophic lateral sclerosis (sporadic)	2.000000e-06
GCST002748_14	Epithelial ovarian cancer	2.000000e-08
GCST002748_19	Epithelial ovarian cancer	2.000000e-08
GCST006627_72	Diastolic blood pressure	3.000000e-09
GCST006979_450	Heel bone mineral density	3.000000e-09
GCST007648_5	Estimated glomerular filtration rate after 5 years in renal transplantation (donor effect)	4.000000e-06
GCST010396_216	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06
GCST012171_2	Aortic vascular smooth muscle cell calcification in response to osteogenic stimuli	3.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0005199	renal transplant outcome measurement
EFO:0007892	donor genotype effect measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Valproic Acid	increases expression	4
bisphenol F	affects cotreatment, increases methylation, increases expression	2
bisphenol A	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Tretinoin	increases expression	2
FR900359	increases phosphorylation	1
methyleugenol	decreases expression	1
trichostatin A	increases expression	1
trimellitic anhydride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Dasatinib	increases expression	1
Temozolomide	affects response to substance	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Glyphosate	affects methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenicals	increases expression	1
Benzo(a)pyrene	affects methylation	1
Bleomycin	affects expression	1
Camptothecin	increases expression	1
Carmustine	affects response to substance	1
Dactinomycin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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