MVP

Summary

MVP (major vault protein, HGNC:7531) is a protein-coding gene on chromosome 16p11.2, encoding Major vault protein (Q14764). Required for normal vault structure.

This gene encodes the major component of the vault complex. Vaults are multi-subunit ribonucleoprotein structures that may be involved in nucleo-cytoplasmic transport. The encoded protein may play a role in multiple cellular processes by regulating the MAP kinase, JAK/STAT and phosphoinositide 3-kinase/Akt signaling pathways. The encoded protein also plays a role in multidrug resistance, and expression of this gene may be a prognostic marker for several types of cancer. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 9961 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 151 total — 4 pathogenic
• MANE Select transcript: NM_005115

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7531
Approved symbol	MVP
Name	major vault protein
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	LRP, VAULT1
Ensembl gene	ENSG00000013364
Ensembl biotype	protein_coding
OMIM	605088
Entrez	9961

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 16 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000357402, ENST00000395353, ENST00000562463, ENST00000563096, ENST00000563123, ENST00000563558, ENST00000563915, ENST00000565164, ENST00000565830, ENST00000566066, ENST00000566252, ENST00000566554, ENST00000566859, ENST00000568068, ENST00000569612, ENST00000569887, ENST00000570061, ENST00000570234, ENST00000852129, ENST00000852130, ENST00000852131, ENST00000852132, ENST00000852133, ENST00000852134, ENST00000949029, ENST00000949030

RefSeq mRNA: 4 — MANE Select: NM_005115 NM_001293204, NM_001293205, NM_005115, NM_017458

CCDS: CCDS10656

Canonical transcript exons

ENST00000357402 — 15 exons

Exon	Start	End
ENSE00000681478	29833935	29834066
ENSE00001668720	29844493	29844879
ENSE00001686549	29841915	29842112
ENSE00001706097	29846158	29846284
ENSE00001781320	29845863	29845979
ENSE00001783042	29847197	29847385
ENSE00001801748	29820462	29820510
ENSE00003483921	29833733	29833856
ENSE00003559624	29840178	29840459
ENSE00003583755	29836722	29836958
ENSE00003642888	29830515	29830674
ENSE00003649043	29841596	29841840
ENSE00003669765	29835704	29835798
ENSE00003691011	29830878	29831073
ENSE00003847321	29847762	29848021

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.7462 / max 525.9354, expressed in 1718 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153543	74.6649	1680
153542	7.0997	1482
153552	0.7167	465
153545	0.5665	309
153554	0.5093	275
153553	0.4349	235
153551	0.3612	178
153544	0.1601	53
153547	0.0851	24
153548	0.0595	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.19	gold quality
right adrenal gland	UBERON:0001233	98.78	gold quality
left adrenal gland	UBERON:0001234	98.73	gold quality
granulocyte	CL:0000094	98.71	gold quality
left adrenal gland cortex	UBERON:0035825	98.71	gold quality
right adrenal gland cortex	UBERON:0035827	98.69	gold quality
transverse colon	UBERON:0001157	98.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.37	gold quality
adrenal cortex	UBERON:0001235	98.12	gold quality
colonic epithelium	UBERON:0000397	98.04	gold quality
upper lobe of left lung	UBERON:0008952	97.94	gold quality
stromal cell of endometrium	CL:0002255	97.87	gold quality
right ovary	UBERON:0002118	97.81	gold quality
small intestine	UBERON:0002108	97.79	gold quality
gall bladder	UBERON:0002110	97.74	gold quality
rectum	UBERON:0001052	97.73	gold quality
left ovary	UBERON:0002119	97.73	gold quality
monocyte	CL:0000576	97.72	gold quality
upper lobe of lung	UBERON:0008948	97.68	gold quality
adrenal gland	UBERON:0002369	97.67	gold quality
right lung	UBERON:0002167	97.49	gold quality
metanephros cortex	UBERON:0010533	97.39	gold quality
leukocyte	CL:0000738	97.37	gold quality
body of stomach	UBERON:0001161	97.36	gold quality
mononuclear cell	CL:0000842	97.35	gold quality
mucosa of stomach	UBERON:0001199	97.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.23	gold quality
endocervix	UBERON:0000458	97.22	gold quality
oocyte	CL:0000023	97.15	gold quality
body of pancreas	UBERON:0001150	97.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, MYOD1, SP1, STAT1, TP53, USF1, YBX1

Literature-anchored findings (GeneRIF, showing 40)

• MVP gene expression regulated by alternative splicing due to generation of an upstream open reading frame (PMID:11297743)
• findings suggest that Tax-related drug resistance of ATL cells is due to LRP and not MDR1, as reported previously. (PMID:11937269)
• relationship between the expression of lung resistance-related protein (lrp) gene or multidrug resistance-associated protein (mrp) gene and prognosis in untreated acute leukemia (AL) patients (PMID:11940320)
• LRP/MVP mRNA expression decreased as AML disease evolved, suggesting it is not associated with clinical resistant disease in AML. (PMID:11986944)
• identification as a dominant PTEN-binding protein in a yeast two-hybrid screen (PMID:12177006)
• RNA expression of this protein in breast cancer correlates with response to chemotherapy. (PMID:12576456)
• expression of lung resistance-related protein in differentiated cells and subsequent expression after chemotherapy suggests that it plays a role in therapy-induced differentiation (PMID:12612883)
• neither the presence nor the degree of immunoreactivity to MVP/LRP showed any correlation with either tumor grade or the presence of brain invasion (PMID:12622134)
• In gangliogliomas, western blot analysis showed a consistent increase in major vault protein expression compared with control cortex. (PMID:12919388)
• MVP and BCRP were expressed ubiquitously in brain capillary endothelium. Ectopic upregulation of MVP was seen in hilar neurons in HS, dysplastic neurons in FCD, and lesional neurons in DNT. Only in HS cases were rare extralesional neurons immunoreactive. (PMID:14636345)
• Results suggest that major vault protein functions as a novel scaffold protein for both SHP-2 and Erk. (PMID:15133037)
• The inverted MED1 element and the LRP130 protein have a role in transcription of the MVP gene. (PMID:15272088)
• Expression of LRP tended to be down-regulated in carcinomas. Moreover, the expression of LRP inversely correlated with tumor grades. (PMID:15379935)
• Vaults play no direct role in the multiple drug resistance phenotype in non-small cell lung carcinoma cells; their cellular function remains unknown. (PMID:15709737)
• MVP is localized to the cell nucleus in an astrocytoma cell line. (PMID:15902504)
• The nasopharyngeal carcinoma patients with positive LRP and TS expression may be less sensitive to chemotherapy with DDP + 5-FU. (PMID:15952572)
• Results report the structure of the main repeat element in human major vault protein. (PMID:16373071)
• Data show that the interaction between Src and major vault protein (MVP) is critically dependent on Src activity and protein (MVP) tyrosyl phosphorylation, which are induced by epidermal growth factor stimulation. (PMID:16441665)
• The expression of mRNA for MDR1 and LRP was determined in bone marrow samples from control, de novo acute myelocytic leukemia, myelodysplastic syndrome(MDS), MDS at the time of overt leukemia(OL) transformation (MDS –> OL),and after transformation (OL). (PMID:16566920)
• LRP expression affects complete remission and survival rates in acute leukemia (PMID:16614510)
• Taken together, these results suggest that ZNF540 may act as a transcriptional repressor in MAPK signaling pathway to mediate cellular functions. (PMID:16815308)
• LRP was highly expressed and is associated with adult T-cell leukemia/lymphoma (PMID:17134750)
• PTEN reportedly interacts in vitro with the EF hand-like motif of major vault protein in a Ca(2+)-dependent manner in a breast tumor cell line. (PMID:17178862)
• Sequence analysis and molecular modeling were used to show that MVP and the toxic anion resistance protein, TelA of Rhodobacter sphaeroides strain 2.4.1, share a novel fold that consists of a three-stranded antiparallel beta-sheet. (PMID:17337707)
• MVP expression is involved in one of the mechanisms of drug resistance in osteosarcoma and is induced by chemotherapy (PMID:17415755)
• results suggest that LRP expression observed in NSCLC, maintained through the carcinogenesis process of respiratory cells, is not altered by the increased number of copies of chromosome 16. (PMID:17438350)
• results report that MVP is rapidly recruited to lipid rafts when lung epithelial cells are infected with Pseudomonas aeruginosa; MVP was also essential for optimal epithelial cell internalization and clearance of P. aeruginosa (PMID:17615361)
• statistically significant correlations between MRP1 and LRP expression and between MRP1 or LRP expression and MDR1 expression (PMID:17875533)
• Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia. (PMID:18200595)
• MVP and IGF-1R expression were related in clinical cervical tumours and confer reduced long-term local control in patients who achieved clinical complete response to radiochemotherapy. (PMID:18599112)
• MVP is important in the resistance of senescent human diploid fibroblasts to apoptosis by modulation of Bcl-2 expression by c-Jun NH(2)-terminal kinase pathway. (PMID:18600231)
• In multiple myeloma, chemotherapy induces integrin beta-1 expression which in turn upregulates LRP, leading to antineoplastic drug resistance. (PMID:18615555)
• Data demonstrate that exposure of cells to hyperosmotic stress induces major vault protein, which might play a role in protecting cells from the adverse effects of osmotic stress. (PMID:18671966)
• Our study reports expression of MRP and LRP in nasal NK/T-cell lymphoma (PMID:18972317)
• The expression of EGFR and LRP could be used to predict chemotherapy resistance and prognosis of ovarian cancer. (PMID:19080004)
• MVP is involved in intracellular signaling, cell survival, differentiation a& innate immunity. Age-related upregulation of MVP facilitates apoptosis resistance. Review. (PMID:19335069)
• Tumor Suppressor Protein p53 contributes to the major vault protein -facilitated resistance to apoptosis by senescent human diploid fibroblasts by transcriptionally activating MVP gene in these cells. (PMID:19472297)
• P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated non-Hodgkin’s lymphoma. (PMID:19615260)
• tumor hypoxia is associated with high major vault protein expression in clinical cervical tumors (PMID:19660100)
• mRNA expression predicts chemotherapy response and survival in patients with non-small cell lung cancer who received neoadjuvant cisplatin-based chemotherapy (PMID:19875192)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mvp	ENSDARG00000021242
mus_musculus	Mvp	ENSMUSG00000030681
rattus_norvegicus	Mvp	ENSRNOG00000020182

Protein

Protein identifiers

Major vault protein — Q14764 (reviewed: Q14764)

Alternative names: Lung resistance-related protein

All UniProt accessions (12): Q14764, H3BNF2, H3BNF6, H3BP76, H3BPZ2, H3BQE7, H3BQK6, H3BRL2, H3BUK7, H3BUP3, I3L155, X5D2M8

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases.

Subunit / interactions. The vault ribonucleoprotein particle is a huge (400 A x 670 A) cage structure of 12.9 MDa. It consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains, PARP4 and one or more vault RNAs (vRNAs). Interacts with TEP1. Interacts with PTEN and activated MAPK1. The phosphorylated protein interacts with the SH2 domains of PTPN11 and SRC. Interacts with APEX1. May interact with ZNF540.

Subcellular location. Cytoplasm. Nucleus. Nuclear pore complex. Perinuclear region.

Tissue specificity. Present in most normal tissues. Higher expression observed in epithelial cells with secretory and excretory functions, as well as in cells chronically exposed to xenobiotics, such as bronchial cells and cells lining the intestine. Overexpressed in many multidrug-resistant cancer cells.

Post-translational modifications. Phosphorylated on Tyr residues after EGF stimulation. Dephosphorylated by PTPN11.

Domain organisation. MVP 3 mediates interaction with PTEN. MVP 4 mediates interaction with PARP4.

Induction. Up-regulated by IFNG/IFN-gamma.

RefSeq proteins (4): NP_001280133, NP_001280134, NP_005106, NP_059447 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002499	Vault_N	Repeat
IPR021870	MVP_shoulder	Domain
IPR036013	Band_7/SPFH_dom_sf	Homologous_superfamily
IPR039059	MVP	Family
IPR040989	Vault_3	Domain
IPR041134	Vault_2	Domain
IPR041136	Vault_4	Domain
IPR041139	MVP_rep_dom	Domain
IPR043023	MVP_rep_sf	Homologous_superfamily
IPR043179	Vault_2_sf	Homologous_superfamily

Pfam: PF01505, PF11978, PF17794, PF17795, PF17796

UniProt features (88 total): strand 52, repeat 9, helix 9, turn 8, sequence variant 3, modified residue 2, cross-link 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
11EE	ELECTRON MICROSCOPY	1.87
11FH	ELECTRON MICROSCOPY	1.92
11JC	ELECTRON MICROSCOPY	1.96
11JB	ELECTRON MICROSCOPY	2.16
11EQ	ELECTRON MICROSCOPY	2.17
11DV	ELECTRON MICROSCOPY	2.33
11JD	ELECTRON MICROSCOPY	2.37
11DR	ELECTRON MICROSCOPY	2.62
9MXV	ELECTRON MICROSCOPY	2.68
11JF	ELECTRON MICROSCOPY	2.85
9BW6	ELECTRON MICROSCOPY	2.9
9BW7	ELECTRON MICROSCOPY	2.9
9MXH	ELECTRON MICROSCOPY	3.07
9QW9	ELECTRON MICROSCOPY	3.09
9R86	ELECTRON MICROSCOPY	3.1
9BW5	ELECTRON MICROSCOPY	3.3
9MXJ	ELECTRON MICROSCOPY	3.49
9R87	ELECTRON MICROSCOPY	3.6
9QWQ	ELECTRON MICROSCOPY	4.45
1Y7X	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14764-F1	81.87	0.33

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 (4): 2, 445, 444, 704

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 202 (showing top): GOBP_PROTEIN_ACTIVATION_CASCADE, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_SECRETORY_GRANULE, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, MODULE_45, GOZGIT_ESR1_TARGETS_DN, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_PROTEIN_MATURATION, GOBP_ERBB_SIGNALING_PATHWAY, chr16p11, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT

GO Biological Process (9): cell population proliferation (GO:0008283), protein transport (GO:0015031), intracellular signal transduction (GO:0035556), ERBB signaling pathway (GO:0038127), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), mRNA transport (GO:0051028), protein activation cascade (GO:0072376), negative regulation of protein autophosphorylation (GO:0031953), negative regulation of protein tyrosine kinase activity (GO:0061099)

GO Molecular Function (4): protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (12): extracellular region (GO:0005576), nucleus (GO:0005634), nuclear pore (GO:0005643), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), membrane (GO:0016020), secretory granule lumen (GO:0034774), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular anatomical structure	2
negative regulation of protein kinase activity	2
cytoplasm	2
cellular process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
RNA transport	1
protein maturation	1
negative regulation of protein phosphorylation	1
regulation of protein autophosphorylation	1
protein autophosphorylation	1
protein tyrosine kinase activity	1
negative regulation of peptidyl-tyrosine phosphorylation	1
regulation of protein tyrosine kinase activity	1
kinase binding	1
phosphatase binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear envelope	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
protein-containing complex	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MVP	PARP4	Q9UKK3	999
MVP	TEP1	Q99973	997
MVP	PARP1	P09874	766
MVP	ABCB1	P08183	751
MVP	PTEN	P60484	710
MVP	ABCC1	P33527	691
MVP	MYD88	P78397	673
MVP	Q6RUI8	Q6RUI8	572
MVP	ESR1	P03372	548
MVP	ABCG2	Q9UNQ0	506
MVP	EIF2AK3	Q9NZJ5	483
MVP	RIMBP3	Q9UFD9	476
MVP	AGO2	Q9UKV8	466
MVP	ZNF540	Q8NDQ6	466
MVP	PTPN11	Q06124	452

IntAct

140 interactions, top by confidence:

A	B	Type	Score
MVP	MVP	psi-mi:“MI:0915”(physical association)	0.800
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
UBTD2	MVP	psi-mi:“MI:0915”(physical association)	0.560
TOLLIP	MVP	psi-mi:“MI:0915”(physical association)	0.560
MVP	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
MVP	NRF1	psi-mi:“MI:0915”(physical association)	0.560
MVP	DTX2	psi-mi:“MI:0915”(physical association)	0.560
MVP	UBTD2	psi-mi:“MI:0915”(physical association)	0.560
MVP	FNDC3B	psi-mi:“MI:0915”(physical association)	0.560
MVP	TOLLIP	psi-mi:“MI:0915”(physical association)	0.560
MVP	GOPC	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (219): MVP (Two-hybrid), MVP (Affinity Capture-MS), MVP (Synthetic Lethality), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS), MVP (Affinity Capture-MS)

ESM2 similar proteins: A0JWY3, A4H452, A4HSC9, A4WYU7, A8NS89, A9WSI4, B8NHD6, B8ZRF0, C0ZZV2, C6WIC8, C8XAR0, F4IF36, O15706, O50202, O96553, P0DV51, P17255, P23225, P34118, P46509, P53904, P54659, P84193, Q0JKD0, Q14764, Q2UMG1, Q3KRE0, Q3SYU9, Q4CUM2, Q4QJJ7, Q54WZ2, Q54WZ3, Q57Z03, Q5EAJ7, Q5R9N2, Q5T9A4, Q5ZMI4, Q62667, Q69RJ0, Q6P3L0

Diamond homologs: A4H452, A4HSC9, P34118, P54659, Q14764, Q3SYU9, Q4CUM2, Q4QJJ7, Q57Z03, Q5EAJ7, Q5R9N2, Q5ZMI4, Q62667, Q6P3L0, Q6PF69, Q90405, Q9DGM7, Q9EQK5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MVP	“form complex”	“Vault ribonucleoprotein complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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
Transcriptional regulation of granulopoiesis	9	13.4×	1e-05
Packaging Of Telomere Ends	5	13.1×	5e-03
Recognition and association of DNA glycosylase with site containing an affected purine	5	12.1×	5e-03
Cleavage of the damaged purine	5	12.1×	5e-03
Regulation of PD-L1(CD274) transcription	9	11.7×	2e-05
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	5	11.0×	5e-03
Cleavage of the damaged pyrimidine	5	11.0×	5e-03
RHOQ GTPase cycle	5	10.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	14.1×	7e-03
erythrocyte differentiation	5	13.0×	8e-03
response to xenobiotic stimulus	9	6.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	113
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1172563	GRCh37/hg19 16p11.2(chr16:29545794-30307472)x1	Pathogenic
2685573	GRCh37/hg19 16p11.2(chr16:29589674-30226930)x1	Pathogenic
395601	GRCh37/hg19 16p12.3-11.2(chr16:19424115-30142220)x3	Pathogenic
625607	GRCh37/hg19 16p11.2(chr16:29678569-30199578)	Pathogenic

SpliceAI

2016 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29830672:GAG:G	donor_gain	1.0000
16:29830876:A:AG	acceptor_gain	1.0000
16:29830876:AG:A	acceptor_gain	1.0000
16:29830877:G:GG	acceptor_gain	1.0000
16:29830877:GG:G	acceptor_gain	1.0000
16:29831058:G:T	donor_gain	1.0000
16:29831070:AAAG:A	donor_loss	1.0000
16:29831071:AAG:A	donor_loss	1.0000
16:29831072:AG:A	donor_loss	1.0000
16:29831073:GGTA:G	donor_loss	1.0000
16:29831074:GT:G	donor_loss	1.0000
16:29833728:ACTAG:A	acceptor_gain	1.0000
16:29833729:CTA:C	acceptor_loss	1.0000
16:29833731:A:AG	acceptor_gain	1.0000
16:29833731:A:G	acceptor_loss	1.0000
16:29833731:AG:A	acceptor_gain	1.0000
16:29833732:G:GG	acceptor_gain	1.0000
16:29833732:GG:G	acceptor_gain	1.0000
16:29833732:GGA:G	acceptor_gain	1.0000
16:29833732:GGAC:G	acceptor_gain	1.0000
16:29833830:GAGA:G	donor_gain	1.0000
16:29833833:A:G	donor_gain	1.0000
16:29833855:TGG:T	donor_loss	1.0000
16:29833856:GGT:G	donor_loss	1.0000
16:29833857:G:GA	donor_loss	1.0000
16:29833857:G:GG	donor_gain	1.0000
16:29833858:TAAGT:T	donor_loss	1.0000
16:29833933:A:AC	acceptor_loss	1.0000
16:29833933:A:AG	acceptor_gain	1.0000
16:29833933:AG:A	acceptor_gain	1.0000

AlphaMissense

5754 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:29844632:C:G	H592D	1.000
16:29844819:T:C	L654P	1.000
16:29844837:T:C	L660P	1.000
16:29844843:T:A	I662N	1.000
16:29844860:T:C	S668P	1.000
16:29844869:G:C	A671P	1.000
16:29844875:G:C	A673P	1.000
16:29845891:G:C	A684P	1.000
16:29846195:G:C	A726P	1.000
16:29841926:G:A	G483E	0.999
16:29842082:C:A	A535D	0.999
16:29842088:T:C	L537P	0.999
16:29842111:T:A	W545R	0.999
16:29842111:T:C	W545R	0.999
16:29844620:T:C	F588L	0.999
16:29844621:T:G	F588C	0.999
16:29844622:C:A	F588L	0.999
16:29844622:C:G	F588L	0.999
16:29844630:T:C	F591S	0.999
16:29844810:G:C	R651P	0.999
16:29844815:G:C	A653P	0.999
16:29844819:T:A	L654Q	0.999
16:29844825:G:C	R656P	0.999
16:29844831:T:A	V658D	0.999
16:29844839:G:C	A661P	0.999
16:29844840:C:A	A661D	0.999
16:29844843:T:G	I662S	0.999
16:29844849:T:C	I664T	0.999
16:29844849:T:G	I664S	0.999
16:29844864:A:C	Q669P	0.999

dbSNP variants (sampled 300 via entrez): RS1000028521 (16:29833498 G>A), RS1000170079 (16:29845451 C>G,T), RS1000197357 (16:29823680 C>G,T), RS1000534770 (16:29839612 A>G), RS1000551883 (16:29822991 T>C), RS1000808122 (16:29822750 C>T), RS1000848620 (16:29835365 G>A), RS1000883393 (16:29823410 G>T), RS1001039451 (16:29835008 A>G), RS1001046559 (16:29847445 C>G), RS1001205160 (16:29827827 G>A), RS1001263439 (16:29821930 G>A), RS1001333614 (16:29828291 T>A,C,G), RS1001343244 (16:29835608 G>A), RS1001352779 (16:29834529 C>G,T)

Disease associations

OMIM: gene MIM:605088 | disease phenotypes: MIM:614671

GenCC curated gene-disease

Mondo (1): chromosome 16p11.2 duplication syndrome (MONDO:0013847)

Orphanet (1): Proximal 16p11.2 microduplication syndrome (Orphanet:370079)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90020029_565	Waist circumference adjusted for body mass index	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1057451	LRP1, MVP, PAGR1		0.00	0
rs4788184	LRP1, MVP, PAGR1		0.00	0
rs4788186	LRP1, MVP		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, affects cotreatment, affects methylation	6
Tetrachlorodibenzodioxin	increases expression	3
sodium arsenite	increases expression	2
Temozolomide	decreases response to substance, increases expression, decreases expression, affects cotreatment	2
Zoledronic Acid	increases expression, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cisplatin	decreases response to substance, increases expression, affects cotreatment	2
Doxorubicin	decreases expression, affects response to substance	2
Fluorouracil	affects binding, increases reaction, affects cotreatment, decreases response to substance, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
polymarcine	decreases response to substance, increases expression, affects cotreatment	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
decamethrin	increases expression, affects cotreatment, decreases response to substance	1
ferrous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
epigallocatechin gallate	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1XZ	Abcam HeLa MVP KO	Cancer cell line	Female
CVCL_D7VD	Ubigene A-549 MVP KO	Cancer cell line	Male
CVCL_SZ50	HAP1 MVP (-) 1	Cancer cell line	Male
CVCL_SZ51	HAP1 MVP (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight