VASH2

Summary

VASH2 (vasohibin 2, HGNC:25723) is a protein-coding gene on chromosome 1q32.3, encoding Tubulinyl-Tyr carboxypeptidase 2 (Q86V25). Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function.

Enables actin binding activity; metallocarboxypeptidase activity; and microtubule binding activity. Involved in axon development and proteolysis. Acts upstream of or within cell-cell fusion; positive regulation of angiogenesis; and positive regulation of endothelial cell proliferation. Located in cytosol.

Source: NCBI Gene 79805 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 55 total — 1 pathogenic
• MANE Select transcript: NM_001301056

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25723
Approved symbol	VASH2
Name	vasohibin 2
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12505
Ensembl gene	ENSG00000143494
Ensembl biotype	protein_coding
OMIM	610471
Entrez	79805

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000271776, ENST00000366964, ENST00000366965, ENST00000366966, ENST00000366967, ENST00000366968, ENST00000366969, ENST00000481097, ENST00000490792, ENST00000493155, ENST00000517399, ENST00000519906, ENST00000917479, ENST00000917480, ENST00000917481, ENST00000917482, ENST00000917483, ENST00000917484, ENST00000917485, ENST00000917486, ENST00000917487, ENST00000917488, ENST00000917489, ENST00000917490, ENST00000917491

RefSeq mRNA: 4 — MANE Select: NM_001301056 NM_001136474, NM_001136475, NM_001301056, NM_024749

CCDS: CCDS1511, CCDS44315, CCDS44316, CCDS73026

Canonical transcript exons

ENST00000517399 — 8 exons

Exon	Start	End
ENSE00001068457	212951339	212951818
ENSE00001443139	212988512	212991585
ENSE00002118849	212973955	212974070
ENSE00003509952	212972580	212972961
ENSE00003719847	212966271	212966345
ENSE00003722022	212965722	212965778
ENSE00003722762	212961166	212961254
ENSE00003919619	212950541	212950740

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 95.57.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3966 / max 302.3597, expressed in 834 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8500	3.9341	645
8499	1.1690	464
8501	0.2935	150

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.57	gold quality
sperm	CL:0000019	87.02	gold quality
ganglionic eminence	UBERON:0004023	86.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.53	gold quality
male germ cell	CL:0000015	83.87	gold quality
left testis	UBERON:0004533	79.70	gold quality
right testis	UBERON:0004534	79.14	gold quality
adrenal tissue	UBERON:0018303	78.46	gold quality
testis	UBERON:0000473	78.21	gold quality
embryo	UBERON:0000922	76.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.88	gold quality
parietal pleura	UBERON:0002400	75.68	gold quality
ventricular zone	UBERON:0003053	74.85	gold quality
buccal mucosa cell	CL:0002336	74.07	gold quality
tibia	UBERON:0000979	71.95	gold quality
pleura	UBERON:0000977	71.51	gold quality
gall bladder	UBERON:0002110	70.23	gold quality
pituitary gland	UBERON:0000007	69.65	gold quality
vermiform appendix	UBERON:0001154	68.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	68.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	68.82	gold quality
lower esophagus	UBERON:0013473	68.81	gold quality
mucosa of stomach	UBERON:0001199	68.38	gold quality
adenohypophysis	UBERON:0002196	68.21	gold quality
ectocervix	UBERON:0012249	68.15	gold quality
lymph node	UBERON:0000029	67.71	gold quality
body of uterus	UBERON:0009853	67.71	gold quality
endocervix	UBERON:0000458	67.61	gold quality
granulocyte	CL:0000094	67.44	gold quality
smooth muscle tissue	UBERON:0001135	67.42	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	190.67
E-ANND-3	yes	5.50
E-GEOD-81608	no	9.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

182 targeting VASH2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3613-3P	100.00	76.36	7965
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-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-493-5P	99.96	72.47	2382

Literature-anchored findings (GeneRIF, showing 29)

• vasohibin-1 and vasohibin-2 mRNA are expressed in gastric cancer cells and in tumor-associated macrophages (TAMs), and their expressions are altered by hypoxia. (PMID:22438034)
• VASH2 contributes to the angiogenesis in hepatocellular carcinoma via an Small vasohibin binding protein-mediated paracrine mechanism. (PMID:22614011)
• VASH2 expressed in serous ovarian carcinoma cells promoted tumor growth and peritoneal dissemination by promoting angiogenesis. (PMID:22826464)
• Data suggest that VASH1 is expressed in vascular endothelium to terminate angiogenesis; VASH2 appears to be expressed in other cells (primarily mononuclear leukocytes) to promote angiogenesis. [REVIEW] (PMID:23100270)
• This is the first study to report differences in the intracellular localization of the VASH2 protein and, hence, a new research direction on the study of VASH2 (PMID:23615928)
• VASH2 overexpression downregulated wild-type p53. (PMID:24595063)
• VASH1 and VASH2 showed distinctive localization and opposing function on the fetoplacental vascularization. (PMID:25184477)
• MiR200-upregulated Vasohibin 2 promotes the malignant transformation of tumors by inducing epithelial-mesenchymal transition in hepatocellular carcinoma (PMID:25269476)
• Suggest that overexpression of VASH2 in pancreatic ductal adenocarcinoma accelerated the pace of tumor development toward a more serious malignant phenotype and was associated with a poor clinical outcome. (PMID:25916042)
• to the best of our knowledge, these results are the first clinical data indicating that nuclear VASH2, but not cytoplasmic VASH2, promotes cell proliferation by driving the cell cycle from the G0/G1 to S phase. (PMID:26177649)
• VASH2 expression is positively correlated with FGF2 expression and promotes angiogenesis in human luminal breast cancer by transcriptional activation of fibroblast growth factor 2 through non-paracrine mechanisms. (PMID:27702660)
• identified a novel UPS regulatory system in which essential domain architecture (VASH-PS) of VASHs, comprising regions VASH191-180 and VASH280-169 , regulate the cytosolic punctate structure formation in the absence of SVBP. (PMID:27879017)
• The results indicate that VASH2 played a significant role in the epithelial-mesenchymal transition by modulating the TGF-beta signaling. (PMID:28064471)
• These data suggest that VASH2 reduces the chemosensitivity to gemcitabine in pancreatic cancer cells via JUN-dependent transactivation of RRM2. (PMID:28327155)
• The present study suggests a protective effect of miR-200b/c on high glucose induced human retinal microvascular endothelial cell line dysfunction by inhibiting VASH2. (PMID:28882646)
• These results suggest that VASH2 plays an important role in gastric tumor progression via the accumulation of cancer-associated fibroblasts (PMID:28960674)
• VASH2 may promote drug resistance of breast cancer cells through regulating ABCG2 via the AKT signaling pathway. (PMID:29039601)
• These results suggest that VASH-2 could play an important role in the pathogenesis of renal diseases, and that VASH-2 is closely associated with hypertension and impaired glucose tolerance. (PMID:29042694)
• VASH1 and VASH2 but not SVBP alone, increased detyrosination of -tubulin, and purified vasohibins removed the C-terminal tyrosine of -tubulin. (PMID:29146869)
• Study demonstrates that VASH2 promotes malignant behaviors of pancreatic cancer cells by inducing EMT via activation of the Hedgehog signaling pathway. (PMID:30318866)
• VASH2 Promotes Cell Proliferation and Resistance to Doxorubicin in Non-Small Cell Lung Cancer via AKT Signaling. (PMID:30940294)
• VASH2 promotes tumor angiogenesis as a result of paracrine activity and evasion of tumor immunity as a result of altered gene expression in pancreatic ductal adenocarcinoma cells. (PMID:31074083)
• This study examined the crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal alpha-tubulin peptide. (PMID:31235911)
• Prognostic significance of vasohibin-1 and vasohibin-2 immunohistochemical expression in gastric cancer. (PMID:32494966)
• Vasohibin-1 and -2 in pulmonary lymphangioleiomyomatosis (LAM) cells associated with angiogenic and prognostic factors. (PMID:35026646)
• [Vasohibin-2 promotes proliferation and metastasis of cervical cancer cells by regulating epithelial-mesenchymal transition]. (PMID:35869758)
• Pathological Study on the Expression of Vasohibins in Peripheral Artery Disease. (PMID:35922907)
• A preliminary study on the mechanism of VASH2 in childhood medulloblastoma. (PMID:37821528)
• High Vasohibin-2 expression correlated with autophagy in proliferative diabetic retinopathy. (PMID:38278467)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vash2	ENSDARG00000007774
mus_musculus	Vash2	ENSMUSG00000037568
rattus_norvegicus	Vash2	ENSRNOG00000003832

Paralogs (1): VASH1 (ENSG00000071246)

Protein

Protein identifiers

Tubulinyl-Tyr carboxypeptidase 2 — Q86V25 (reviewed: Q86V25)

Alternative names: Vasohibin-2, Vasohibin-like protein

All UniProt accessions (3): Q86V25, A0A140VJZ5, C9JY36

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function. Critical for spindle function and accurate chromosome segregation during mitosis since microtubule detyronisation regulates mitotic spindle length and postioning. Acts as an activator of angiogenesis: expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis. Plays a role in axon formation.

Subunit / interactions. Interacts with SVBP; interaction enhances VASH2 tyrosine carboxypeptidase activity.

Subcellular location. Cytoplasm. Secreted. Cytoskeleton.

Induction. By VEGF.

Similarity. Belongs to the transglutaminase-like superfamily. Vasohibin family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q86V25-1	1	yes
Q86V25-2	2
Q86V25-3	3
Q86V25-4	4
Q86V25-5	5
Q86V25-6	6

RefSeq proteins (4): NP_001129946, NP_001129947, NP_001287985, NP_079025 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028131	VASH1	Family

Pfam: PF14822

Catalyzed reactions (Rhea), 1 shown:

• C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-L-tyrosyl-[tubulin] + H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + L-tyrosine (RHEA:57444)

UniProt features (46 total): mutagenesis site 12, splice variant 8, helix 8, strand 8, active site 3, region of interest 2, compositionally biased region 2, chain 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6J4P	X-RAY DIFFRACTION	1.6
6QBY	X-RAY DIFFRACTION	2.09
6J4V	X-RAY DIFFRACTION	2.1
6J4O	X-RAY DIFFRACTION	2.3
6J4Q	X-RAY DIFFRACTION	2.7
6J4S	X-RAY DIFFRACTION	2.8
7ZCW	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V25-F1	81.46	0.70

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 (3): 158; 193; 210

Post-translational modifications (1): 302

Mutagenesis-validated functional residues (12):

Position	Phenotype
63–67	disrupted interaction with svbp. reduced tyrosine carboxypeptidase activity.
123	reduced tyrosine carboxypeptidase activity.
134	slightly reduced tyrosine carboxypeptidase activity.
135	reduced tyrosine carboxypeptidase activity.
154–155	disrupted interaction with svbp. reduced tyrosine carboxypeptidase activity.
157	reduced tyrosine carboxypeptidase activity.
158	abolished tyrosine carboxypeptidase activity. no effect on binding to microtubule.
192	no effect on tyrosine carboxypeptidase activity.
193	strongly reduced tyrosine carboxypeptidase activity.
210	reduced tyrosine carboxypeptidase activity.
211	reduced tyrosine carboxypeptidase activity.
215	slightly reduced tyrosine carboxypeptidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin

MSigDB gene sets: 183 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_NEUROGENESIS, MODULE_503, GOBP_PLACENTA_BLOOD_VESSEL_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, MODULE_195, GOBP_LABYRINTHINE_LAYER_BLOOD_VESSEL_DEVELOPMENT, GOBP_BLOOD_VESSEL_MORPHOGENESIS, RICKMAN_HEAD_AND_NECK_CANCER_A, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (10): syncytium formation by cell-cell fusion (GO:0000768), positive regulation of endothelial cell proliferation (GO:0001938), proteolysis (GO:0006508), regulation of angiogenesis (GO:0045765), positive regulation of angiogenesis (GO:0045766), labyrinthine layer blood vessel development (GO:0060716), axon development (GO:0061564), cell-cell fusion (GO:0140253), placenta blood vessel development (GO:0060674), labyrinthine layer development (GO:0060711)

GO Molecular Function (8): actin binding (GO:0003779), metallocarboxypeptidase activity (GO:0004181), microtubule binding (GO:0008017), tubulin-tyrosine carboxypeptidase activity (GO:0106423), carboxypeptidase activity (GO:0004180), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (4): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
angiogenesis	2
cell-cell fusion	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
protein metabolic process	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
embryonic organ development	1
placenta blood vessel development	1
labyrinthine layer development	1
neuron projection development	1
cellular process	1
blood vessel development	1
placenta development	1
embryonic placenta development	1
anatomical structure development	1
cytoskeletal protein binding	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
tubulin binding	1
metallocarboxypeptidase activity	1
exopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VASH2	SVBP	Q8N300	862
VASH2	TTL	Q8NG68	607
VASH2	FGF13	Q92913	604
VASH2	FGF2	P09038	587
VASH2	HSF2	Q03933	432
VASH2	PODXL2	Q9NZ53	320
VASH2	GCM1	Q9NP62	306
VASH2	IFNG	P01579	300
VASH2	TTLL8	A6PVC2	280
VASH2	EIF4E2	O60573	278
VASH2	NDNF	Q8TB73	269
VASH2	MAP4	P27816	265
VASH2	WNT2B	Q93097	262
VASH2	WDR88	Q6ZMY6	258
VASH2	SLC25A12	O75746	251

IntAct

14 interactions, top by confidence:

A	B	Type	Score
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
VASH2	YWHAH	psi-mi:“MI:0914”(association)	0.530
VASH2	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
VASH2	NEIL1	psi-mi:“MI:0915”(physical association)	0.400
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
MAP2K2	IPO5	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): NME2P1 (Affinity Capture-MS), VASH2 (Reconstituted Complex), YWHAH (Affinity Capture-MS), VASH2 (Affinity Capture-MS), VASH2 (Affinity Capture-MS), RHEB (Affinity Capture-MS), VASH2 (Affinity Capture-MS), VASH2 (Affinity Capture-MS), VASH2 (Affinity Capture-MS), NEIL1 (Affinity Capture-MS), VASH2 (Affinity Capture-MS), VASH2 (Cross-Linking-MS (XL-MS)), VASH2 (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A4FUD6, A4FVD8, A6QQL9, A7YWS7, B2GUZ5, B5KFI0, O22969, O54956, O95803, P11497, P13984, P16254, P16255, P21282, P21283, P37108, P52865, P52907, P56282, Q01750, Q13085, Q1RMS5, Q28H91, Q29S16, Q2T9L9, Q2TAD4, Q4R5C7, Q4R5H9, Q4R959, Q5FVI6, Q5NVM0, Q5RBS7, Q5RBX7, Q5RCC1, Q5RDQ7, Q5SQF8, Q5SWU9, Q5ZKQ6, Q6NYV5, Q7T385

Diamond homologs: Q7L8A9, Q86V25, Q8C1W1, Q8C5G2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
Viral Infection Pathways	5	14.0×	7e-05
Infectious disease	6	13.5×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	5	43.6×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
832455	NC_000001.11:g.(?212782372)(212951818_?)del	Pathogenic

SpliceAI

1992 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212966358:T:G	donor_gain	1.0000
1:212973949:CTTCA:C	acceptor_loss	1.0000
1:212973950:TTCAG:T	acceptor_loss	1.0000
1:212973952:CA:C	acceptor_loss	1.0000
1:212973953:A:AG	acceptor_gain	1.0000
1:212973954:G:GA	acceptor_gain	1.0000
1:212974066:AAGTC:A	donor_gain	1.0000
1:212974068:GTC:G	donor_gain	1.0000
1:212974069:TC:T	donor_gain	1.0000
1:212974071:G:GG	donor_gain	1.0000
1:212951814:CAAAG:C	donor_loss	0.9900
1:212951815:AAAG:A	donor_loss	0.9900
1:212951817:AGG:A	donor_loss	0.9900
1:212951820:T:G	donor_loss	0.9900
1:212961164:A:AG	acceptor_gain	0.9900
1:212961165:G:GA	acceptor_gain	0.9900
1:212961165:GC:G	acceptor_gain	0.9900
1:212961165:GCCTT:G	acceptor_gain	0.9900
1:212966343:C:T	donor_gain	0.9900
1:212973954:GAT:G	acceptor_gain	0.9900
1:212973954:GATC:G	acceptor_gain	0.9900
1:212973954:GATCC:G	acceptor_gain	0.9900
1:212974067:AGTC:A	donor_gain	0.9900
1:212974068:GTCG:G	donor_gain	0.9900
1:212974068:GTCGT:G	donor_loss	0.9900
1:212974069:TCG:T	donor_loss	0.9900
1:212974069:TCGT:T	donor_gain	0.9900
1:212974072:T:TG	donor_loss	0.9900
1:212974073:G:GT	donor_loss	0.9900
1:212974074:A:AA	donor_loss	0.9900

AlphaMissense

2338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212951741:T:A	W67R	1.000
1:212951741:T:C	W67R	1.000
1:212965723:T:C	Y123H	1.000
1:212965724:A:G	Y123C	1.000
1:212965726:A:G	N124D	1.000
1:212965728:T:A	N124K	1.000
1:212965728:T:G	N124K	1.000
1:212965729:C:G	H125D	1.000
1:212965735:G:A	G127R	1.000
1:212965735:G:C	G127R	1.000
1:212965735:G:T	G127W	1.000
1:212965736:G:A	G127E	1.000
1:212965736:G:T	G127V	1.000
1:212966285:C:A	A146E	1.000
1:212966294:T:G	M149R	1.000
1:212966312:C:A	P155H	1.000
1:212966315:T:A	I156N	1.000
1:212966317:A:G	K157E	1.000
1:212966318:A:T	K157I	1.000
1:212966319:A:C	K157N	1.000
1:212966319:A:T	K157N	1.000
1:212966320:T:C	C158R	1.000
1:212966321:G:A	C158Y	1.000
1:212966322:C:G	C158W	1.000
1:212966324:T:A	L159H	1.000
1:212966324:T:C	L159P	1.000
1:212966326:G:A	E160K	1.000
1:212966327:A:T	E160V	1.000
1:212966329:G:C	A161P	1.000
1:212966339:T:C	L164P	1.000

dbSNP variants (sampled 300 via entrez): RS1000016203 (1:212949214 C>T), RS1000025293 (1:212975179 T>C), RS1000033660 (1:212961639 G>T), RS1000065266 (1:212960447 T>G), RS1000077727 (1:212975490 G>A,C), RS1000105658 (1:212967618 C>T), RS1000289761 (1:212951572 C>A), RS1000311346 (1:212950763 C>T), RS1000319915 (1:212961867 T>C), RS1000356950 (1:212991060 T>C), RS1000391927 (1:212951021 C>T), RS1000412874 (1:212956960 A>G), RS1000441184 (1:212957365 C>G,T), RS1000551431 (1:212957972 G>C), RS1000621919 (1:212979688 G>A,C)

Disease associations

OMIM: gene MIM:610471 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001929_1	Eye color	7.000000e-08
GCST007831_6	Anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003949	eye color

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
bisphenol A	increases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	decreases expression	1
NSC 689534	decreases expression, affects binding	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Silicon Dioxide	decreases expression	1
Thiram	increases expression	1

Clinical trials (associated diseases)

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