VASH1

Summary

VASH1 (vasohibin 1, HGNC:19964) is a protein-coding gene on chromosome 14q24.3, encoding Tubulinyl-Tyr carboxypeptidase 1 (Q7L8A9). Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function.

Enables actin binding activity and metallocarboxypeptidase activity. Involved in negative regulation of angiogenesis; negative regulation of blood vessel endothelial cell migration; and proteolysis. Acts upstream of or within several processes, including negative regulation of endothelial cell proliferation; negative regulation of lymphangiogenesis; and regulation of cellular senescence. Located in apical part of cell; endoplasmic reticulum; and extracellular space. Implicated in liver cirrhosis and portal hypertension. Biomarker of liver cirrhosis.

Source: NCBI Gene 22846 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_014909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19964
Approved symbol	VASH1
Name	vasohibin 1
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000071246
Ensembl biotype	protein_coding
OMIM	609011
Entrez	22846

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000167106, ENST00000553518, ENST00000554237, ENST00000554743, ENST00000556038

RefSeq mRNA: 1 — MANE Select: NM_014909 NM_014909

CCDS: CCDS9851

Canonical transcript exons

ENST00000167106 — 7 exons

Exon	Start	End
ENSE00001093927	76777959	76778071
ENSE00001245832	76761468	76763130
ENSE00001320354	76778946	76783015
ENSE00003521489	76775892	76776273
ENSE00003616356	76771190	76771246
ENSE00003650755	76769963	76770051
ENSE00003671589	76773137	76773211

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 95.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9590 / max 162.8225, expressed in 1524 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140731	7.5867	1485
140734	1.3383	571
140732	0.4045	185
140735	0.3386	184
140733	0.2909	168

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	95.17	gold quality
embryo	UBERON:0000922	95.16	gold quality
cortical plate	UBERON:0005343	93.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.96	gold quality
spinal cord	UBERON:0002240	90.68	gold quality
right atrium auricular region	UBERON:0006631	90.01	gold quality
apex of heart	UBERON:0002098	89.48	gold quality
cardiac atrium	UBERON:0002081	88.96	gold quality
right coronary artery	UBERON:0001625	88.36	gold quality
right adrenal gland	UBERON:0001233	87.15	gold quality
amygdala	UBERON:0001876	86.90	gold quality
sural nerve	UBERON:0015488	86.76	gold quality
left adrenal gland cortex	UBERON:0035825	86.49	gold quality
left adrenal gland	UBERON:0001234	86.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.41	gold quality
ventricular zone	UBERON:0003053	86.38	gold quality
hypothalamus	UBERON:0001898	86.08	gold quality
right adrenal gland cortex	UBERON:0035827	85.93	gold quality
cerebellar hemisphere	UBERON:0002245	85.77	gold quality
cerebellar cortex	UBERON:0002129	85.69	gold quality
popliteal artery	UBERON:0002250	85.40	gold quality
tibial artery	UBERON:0007610	85.39	gold quality
adrenal cortex	UBERON:0001235	85.19	gold quality
anterior cingulate cortex	UBERON:0009835	85.19	gold quality
adrenal tissue	UBERON:0018303	85.16	gold quality
right frontal lobe	UBERON:0002810	85.13	gold quality
adrenal gland	UBERON:0002369	85.08	gold quality
substantia nigra	UBERON:0002038	84.82	gold quality
prefrontal cortex	UBERON:0000451	84.72	gold quality
putamen	UBERON:0001874	84.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.89
E-MTAB-7381	no	749.28
E-MTAB-6075	no	310.97
E-GEOD-109979	no	162.10
E-GEOD-124858	no	49.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

217 targeting VASH1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431

Literature-anchored findings (GeneRIF, showing 40)

• Results suggest that KIAA1036, or vasohibin, is an endothelium-derived negative feedback regulator of angiogenesis [vasohibin] (PMID:15467828)
• Recombinant amino-terminal truncated forms of vasohibin retain inhibitory activity of angiogenesis in mouse corneal assay and show strong affinity to heparin. (PMID:16488400)
• vasohibin has an activity to prevent neointimal formation by inhibiting adventitial angiogenesis (PMID:16707096)
• expression of vasohibin in the stromal endothelial cells in human carcinomas. (PMID:18325046)
• vasohibin-1 is associated with neovascularization and may especially play important roles in the regulation of intratumoral angiogenesis in human breast cancer. (PMID:19037993)
• Hypoxia induces VEGF, which induces the production of vasohibin-1 in endothelial cells and inhibits angiogenesis as a negative feedback regulator. (PMID:19057892)
• These results suggest a role for VASH1 in negative feedback regulation of haematopoietic progenitors proliferation during recovery following bone marrow ablation. (PMID:19179360)
• These results suggest that endogenous vasohibin-1 is involved in tumor angiogenesis and exogenous vasohibin-1 blocks sprouting angiogenesis by tumors, matures the remaining vessels, and enhances the antitumor effect of conventional chemotherapy (PMID:19498005)
• Streptozotocin- induced type 1 diabetic mice received intravenous injections of adenoviral vectors encoding VASH-1, which suppressed diabetic retinopathy. (PMID:19587360)
• Overexpression of human VASH1 inhibited angiogenic sprouting and supports vascular maturation processes in vivo. (PMID:19682397)
• These results suggest that vasohibin-1 is expressed in RA synovial tissue and might be regulated by inflammatory cytokines. (PMID:20035291)
• vasohibin1 is the first known intrinsic factor having broad-spectrum antilymphangiogenic activity (PMID:20133819)
• This review focuses on negative regulators of angiogenesis delta-like 4 and vasohibin 1 produced by endothelial cells. (PMID:20167561)
• SVBP(CCDC23)acts as a secretory chaperone for VASH1. (PMID:20736312)
• Reduced vasohibin and VEGF expression may be responsible, at least in part, for the impaired vascular development which occurs during pre-eclampsia. (PMID:21302448)
• Vasohibin-1 and VEGF-A are the most important factors influencing the dismal prognosis based on the modulation of angiogenesis in hepatocellular carcinoma (HCC). (PMID:22101788)
• 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)
• Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft and significantly reduced aberrant angiogenesis. (PMID:22564651)
• Data suggest that vasohibin inhibits cell proliferation of umbilical vein endothelial cells through degradation of HIF-1alpha via proline hydroxylase during oxidative stress. Vasohibin may be a negative feedback regulator of angiogenesis. (PMID:22569265)
• Results suggest that Vasohibin-1 (VASH1)density could become a new biomarker and provide additional prognostic information in patients with upper urinary tract urothelial carcinomas (UTUC). (PMID:22675166)
• we postulate that VASH1 would potentially be a biomarker and a candidate for molecular targeted therapy for patients with renal cell carcinoma (PMID:22865127)
• VASH1 is a critical factor that improves the stress tolerance of ECs via the induction of SOD2 and SIRT1 (PMID:23056314)
• 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)
• novel candidate master regulator of endothelial cell apoptosis (PMID:23324451)
• Vasohibin-1 is a new predictor of disease-free survival in operated patients with renal cell carcinoma. (PMID:23543668)
• VASH1 density represents a clinically relevant predictor of patient prognosis and can be a new biomarker that would provide additional prognostic information in prostate cancer. (PMID:23591203)
• Data show expression of TGF-beta1, TGF-beta2, BMP-4, and BMP-7 was increased in tumor-associated macrophages (TAMs) cocultured with pancreatic cancer cells, and vasohibin-1, VEGF-A, and vVEGF-C expression in pancreatic cancer cells was upregulated by TAMs. (PMID:23651239)
• High Vasohibin-1 expression is associated with colorectal cancer. (PMID:24366689)
• We found that vasohibin-1 and VEGF are up-regulated, in mesentery and liver, in cirrhotic and precirrhotic portal hypertensive rats and cirrhosis patients. (PMID:24390792)
• Vasohibin 1/CD34 could identify the proliferative vessels and could be a useful biomarker for predicting the clinical outcome of hepatocellular carcinoma patients. (PMID:24444468)
• High VASH1 expression is associated with non-small cell lung cancer. (PMID:24748406)
• These results suggest that the renal levels of VASH-1 may be affected by local inflammation, crescentic lesions and VEGFR-2. (PMID:25145408)
• VASH1 and VASH2 showed distinctive localization and opposing function on the fetoplacental vascularization. (PMID:25184477)
• Overexpression of VASH1 in CRC cells increased malignant potential and promoted metastasis. (PMID:25275025)
• Knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo. (PMID:25797264)
• VASH1 expression levels in atheroma reflects both enhanced neovascularization and the inflammatory burden (PMID:25843115)
• VASH1 exerts an antitumor effect on ovarian cancer by inhibiting angiogenesis in the tumor environment (PMID:26460696)
• in this study, the length of tube forming structures of endothelial cells in vitro showed that Vasohibin-1 expression in gastric cancer cells significantly decreased the ability of vessel formation of endothelium cells. (PMID:26666821)
• VASH1 expression inhibited tumor vascularization and growth, not only in high VEGF-producing cells, but also in high PDGF-producing cells, reduced their peritoneal dissemination and ascites, and prolonged the survival time of the host (PMID:26893100)
• Our present findings on VASH1A and VASH1B should provide an innovative approach that would improve the efficacy of antiangiogenic cancer therapy by balancing vascular normalization and pruning. (PMID:27080222)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	VASH1	ENSDARG00000092716
mus_musculus	Vash1	ENSMUSG00000021256
rattus_norvegicus	Vash1	ENSRNOG00000010457

Paralogs (1): VASH2 (ENSG00000143494)

Protein

Protein identifiers

Tubulinyl-Tyr carboxypeptidase 1 — Q7L8A9 (reviewed: Q7L8A9)

Alternative names: Tubulin carboxypeptidase 1, Tyrosine carboxypeptidase 1, Vasohibin-1

All UniProt accessions (2): Q7L8A9, G3V4N9

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 angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis. This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts.

Subunit / interactions. Interacts with SVBP; interaction enhances VASH1 tyrosine carboxypeptidase activity.

Subcellular location. Cytoplasm. Secreted.

Tissue specificity. Preferentially expressed in endothelial cells. Highly expressed in fetal organs. Expressed in brain and placenta, and at lower level in heart and kidney. Highly detected in microvessels endothelial cells of atherosclerotic lesions.

Post-translational modifications. 2 major forms (42 and 36 kDa) and 2 minors (32 and 27 kDa) may be processed by proteolytic cleavage. The largest form (42 kDa) seems to be secreted and the other major form (63 kDa) seems to accumulate within the cells or pericellular milieu. Polypeptide consisting of Met-77 to Arg-318 may correspond to the 27 kDa form and that consisting of Met-77 to Val-365 may correspond to the 36 kDa form. Ubiquitinated in vitro.

Induction. By VEGF.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L8A9-1	1	yes
Q7L8A9-2	2

RefSeq proteins (1): NP_055724* (*=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 (59 total): mutagenesis site 25, strand 10, helix 8, compositionally biased region 4, region of interest 3, active site 3, site 2, splice variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6J7B	X-RAY DIFFRACTION	1.62
6OCG	X-RAY DIFFRACTION	1.83
6J8O	X-RAY DIFFRACTION	1.85
6J8N	X-RAY DIFFRACTION	1.95
6J4U	X-RAY DIFFRACTION	2
6OCH	X-RAY DIFFRACTION	2
6NVQ	X-RAY DIFFRACTION	2.1
6OCF	X-RAY DIFFRACTION	2.1
6K81	X-RAY DIFFRACTION	2.28
6J8F	X-RAY DIFFRACTION	2.28
6LPG	X-RAY DIFFRACTION	2.3
6J9H	X-RAY DIFFRACTION	2.31
6WSL	ELECTRON MICROSCOPY	3.1
6J91	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L8A9-F1	79.44	0.67

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 (5): 221; 29–30 (cleavage); 76–77 (cleavage); 169; 204

Mutagenesis-validated functional residues (25):

Position	Phenotype
29	disappearance of 42 kda processed form.
74–78	strongly reduced interaction with svbp.
76	disappearance of 36, 32 and 27 kda processed forms.
77–81	no effect on tyrosine carboxypeptidase activity on alpha-tubulin.
77	no effect on tyrosine carboxypeptidase activity on alpha-tubulin. reduced tyrosine carboxypeptidase activity on alpha-tu
81	no effect on tyrosine carboxypeptidase activity on alpha-tubulin. reduced tyrosine carboxypeptidase activity on alpha-tu
134	abolished tyrosine carboxypeptidase activity on alpha-tubulin.
141	no effect on tyrosine carboxypeptidase activity on alpha-tubulin. reduced tyrosine carboxypeptidase activity on alpha-tu
145	reduced tyrosine carboxypeptidase activity on alpha-tubulin.
146	abolished tyrosine carboxypeptidase activity on alpha-tubulin. abolished tyrosine carboxypeptidase activity on alpha-tub
165–166	almost abolished interaction with vash1.
168	abolished tyrosine carboxypeptidase activity on alpha-tubulin.
169	abolished tyrosine carboxypeptidase activity on alpha-tubulin.
194	no effect on tyrosine carboxypeptidase activity on alpha-tubulin. no effect on tyrosine carboxypeptidase activity on alp
203	no effect on tyrosine carboxypeptidase activity on alpha-tubulin. strongly reduced tyrosine carboxypeptidase activity on
204	abolished tyrosine carboxypeptidase activity on alpha-tubulin.
221	abolished tyrosine carboxypeptidase activity on alpha-tubulin.
222	abolished tyrosine carboxypeptidase activity on alpha-tubulin. abolished tyrosine carboxypeptidase activity on alpha-tub
222	reduced tyrosine carboxypeptidase activity on alpha-tubulin.
223	slightly reduced tyrosine carboxypeptidase activity on alpha-tubulin.
226	slightly reduced tyrosine carboxypeptidase activity on alpha-tubulin.
247	slightly reduced tyrosine carboxypeptidase activity on alpha-tubulin.
256	no effect on tyrosine carboxypeptidase activity on alpha-tubulin; when associated with e-194. reduced tyrosine carboxype
258	no effect on tyrosine carboxypeptidase activity on alpha-tubulin. no effect on tyrosine carboxypeptidase activity on alp
276	no effect on tyrosine carboxypeptidase activity on alpha-tubulin. no effect on tyrosine carboxypeptidase activity on alp

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 189 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BENPORATH_ES_WITH_H3K27ME3, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_CELLULAR_SENESCENCE, GOBP_PLACENTA_BLOOD_VESSEL_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, chr14q24

GO Biological Process (12): angiogenesis (GO:0001525), negative regulation of endothelial cell proliferation (GO:0001937), proteolysis (GO:0006508), response to wounding (GO:0009611), negative regulation of angiogenesis (GO:0016525), negative regulation of blood vessel endothelial cell migration (GO:0043537), regulation of angiogenesis (GO:0045765), regulation of cell cycle (GO:0051726), labyrinthine layer blood vessel development (GO:0060716), negative regulation of lymphangiogenesis (GO:1901491), regulation of cellular senescence (GO:2000772), placenta blood vessel development (GO:0060674)

GO Molecular Function (7): actin binding (GO:0003779), metallocarboxypeptidase activity (GO:0004181), 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 (5): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), apical part of cell (GO:0045177), extracellular region (GO:0005576)

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
regulation of cellular process	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
protein metabolic process	1
response to stress	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
negative regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
cell cycle	1
embryonic organ development	1
placenta blood vessel development	1
labyrinthine layer development	1
lymphangiogenesis	1
negative regulation of developmental process	1
regulation of lymphangiogenesis	1
cellular senescence	1
blood vessel development	1
placenta development	1
cytoskeletal protein binding	1
carboxypeptidase activity	1
metalloexopeptidase activity	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
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VASH1	SVBP	Q8N300	989
VASH1	ANGEL1	Q9UNK9	845
VASH1	POMT2	Q9UKY4	663
VASH1	TTL	Q8NG68	648
VASH1	FGF2	P09038	574
VASH1	TGFB3	P10600	551
VASH1	FGF13	Q92913	528
VASH1	TMEM43	Q9BTV4	497
VASH1	TUBA1B	P04687	476
VASH1	ANGPT4	Q9Y264	433
VASH1	DSC2	Q02487	423
VASH1	DSC3	Q14574	423
VASH1	ANGPTL7	O43827	410
VASH1	ANGPT1	Q15389	403
VASH1	NDRG1	Q92597	400

IntAct

9 interactions, top by confidence:

A	B	Type	Score
VASH1	DHPS	psi-mi:“MI:0915”(physical association)	0.560
VASH1	TUFM	psi-mi:“MI:0915”(physical association)	0.400
VASH1	HSPA8	psi-mi:“MI:0915”(physical association)	0.400
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
VASH1	PGAM2	psi-mi:“MI:0914”(association)	0.350
VASH1	NAA30	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): VASH1 (Two-hybrid), HSPA8 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA1L (Affinity Capture-MS), AMY1C (Affinity Capture-MS), RAB6B (Affinity Capture-MS), C9orf142 (Affinity Capture-MS), RAP1GDS1 (Affinity Capture-MS), RHOA (Affinity Capture-MS), VASH1 (Synthetic Lethality), VASH1 (Proximity Label-MS), HSPA8 (Affinity Capture-MS), ISOC2 (Affinity Capture-MS), PGAM2 (Affinity Capture-MS), VASH1 (Affinity Capture-MS)

ESM2 similar proteins: A0AUR5, A2VE39, A7E2V1, B0V3H4, B3MCF3, B3NQ86, B4HSF8, B4J8A0, B4KPY6, B4MDT2, B4MQL4, B4P6V4, B4QGZ1, B8AXU2, D2HRF1, O00418, O22944, O60551, O70310, P30419, P31717, Q1LWX3, Q28WL0, Q3T0D3, Q4KLT3, Q4R6F3, Q503I8, Q5BJV9, Q5PPU8, Q5R981, Q5RAF3, Q5U2Z5, Q5XI55, Q5ZJM3, Q60E61, Q6DDX8, Q6GQ76, Q6NX27, Q7F0R1, Q7K2Y9

Diamond homologs: Q7L8A9, Q86V25, Q8C1W1, Q8C5G2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1656 predictions. Top by Δscore:

Variant	Effect	Δscore
14:76763128:AAGGT:A	donor_loss	1.0000
14:76763129:AGGTG:A	donor_loss	1.0000
14:76763130:GGT:G	donor_loss	1.0000
14:76763131:GTGA:G	donor_loss	1.0000
14:76763132:T:A	donor_loss	1.0000
14:76770052:G:GG	donor_gain	1.0000
14:76773131:CCACA:C	acceptor_loss	1.0000
14:76773132:CACAG:C	acceptor_loss	1.0000
14:76773134:CAGG:C	acceptor_loss	1.0000
14:76773135:A:AG	acceptor_gain	1.0000
14:76773135:A:G	acceptor_loss	1.0000
14:76773135:AG:A	acceptor_gain	1.0000
14:76773135:AGGCT:A	acceptor_gain	1.0000
14:76773136:G:GG	acceptor_gain	1.0000
14:76773136:GG:G	acceptor_gain	1.0000
14:76773136:GGCT:G	acceptor_gain	1.0000
14:76773136:GGCTG:G	acceptor_gain	1.0000
14:76773192:G:GT	donor_gain	1.0000
14:76773209:A:T	donor_gain	1.0000
14:76777957:A:AG	acceptor_gain	1.0000
14:76777958:G:GG	acceptor_gain	1.0000
14:76778068:GACG:G	donor_gain	1.0000
14:76778069:ACGG:A	donor_loss	1.0000
14:76778070:CGGTG:C	donor_loss	1.0000
14:76778071:GGTG:G	donor_loss	1.0000
14:76778072:G:GG	donor_gain	1.0000
14:76778072:GTGAG:G	donor_loss	1.0000
14:76778073:T:G	donor_loss	1.0000
14:76770065:TC:T	donor_gain	0.9900
14:76770249:A:G	donor_gain	0.9900

AlphaMissense

2380 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:76771191:T:C	Y134H	1.000
14:76771196:T:A	N135K	1.000
14:76771196:T:G	N135K	1.000
14:76771204:G:A	G138E	1.000
14:76773139:T:C	L153P	1.000
14:76773151:C:A	A157D	1.000
14:76773185:A:C	K168N	1.000
14:76773185:A:T	K168N	1.000
14:76773186:T:C	C169R	1.000
14:76773187:G:A	C169Y	1.000
14:76773188:C:G	C169W	1.000
14:76773193:A:T	E171V	1.000
14:76773195:G:C	A172P	1.000
14:76775939:T:C	F193S	1.000
14:76775945:C:T	T195I	1.000
14:76775971:C:A	H204N	1.000
14:76775971:C:G	H204D	1.000
14:76775972:A:G	H204R	1.000
14:76775973:C:A	H204Q	1.000
14:76775973:C:G	H204Q	1.000
14:76775981:T:C	L207P	1.000
14:76775983:G:T	G208W	1.000
14:76775984:G:A	G208E	1.000
14:76776008:G:A	G216D	1.000
14:76776016:G:C	G219R	1.000
14:76776017:G:A	G219D	1.000
14:76776022:A:C	S221R	1.000
14:76776024:T:A	S221R	1.000
14:76776024:T:G	S221R	1.000
14:76776038:T:C	L226P	1.000

dbSNP variants (sampled 300 via entrez): RS1000052445 (14:76776526 A>G), RS1000104062 (14:76767263 T>G), RS1000214828 (14:76781825 G>A,C), RS1000489191 (14:76776282 G>A,T), RS1000575931 (14:76777495 G>A,C), RS1000583365 (14:76760955 C>A), RS1000584999 (14:76771328 G>A,T), RS1000845518 (14:76766299 C>T), RS1000847014 (14:76766026 G>C), RS1000872658 (14:76772250 A>C,G,T), RS1000926765 (14:76777144 G>A), RS1000942610 (14:76760871 G>C), RS1000944037 (14:76771969 C>T), RS1000951054 (14:76771638 C>T), RS1000980037 (14:76761206 G>C)

Disease associations

OMIM: gene MIM:609011 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
Valproic Acid	affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	increases abundance, increases expression	2
FR900359	affects phosphorylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
gallium arsenide	decreases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Decitabine	affects expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects expression	1
Diazinon	decreases methylation	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Latex	increases expression	1

Clinical trials (associated diseases)

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