PARVA

Summary

PARVA (parvin alpha, HGNC:14652) is a protein-coding gene on chromosome 11p15.3, encoding Alpha-parvin (Q9NVD7). Plays a role in sarcomere organization and in smooth muscle cell contraction.

This gene encodes a member of the parvin family of actin-binding proteins. Parvins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. The encoded protein is part of the integrin-linked kinase signaling complex and plays a role in cell adhesion, motility and survival.

Source: NCBI Gene 55742 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 69 total
• MANE Select transcript: NM_018222

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14652
Approved symbol	PARVA
Name	parvin alpha
Location	11p15.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12254, FLJ10793
Ensembl gene	ENSG00000197702
Ensembl biotype	protein_coding
OMIM	608120
Entrez	55742

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000334956, ENST00000526746, ENST00000528916, ENST00000530755, ENST00000533345, ENST00000533392, ENST00000903580, ENST00000903581, ENST00000903582, ENST00000903583, ENST00000903584, ENST00000903585, ENST00000903586, ENST00000903587, ENST00000912082, ENST00000912083, ENST00000950459

RefSeq mRNA: 1 — MANE Select: NM_018222 NM_018222

CCDS: CCDS44541

Canonical transcript exons

ENST00000334956 — 13 exons

Exon	Start	End
ENSE00001331702	12527849	12535356
ENSE00001403068	12517610	12517711
ENSE00001407717	12513997	12514065
ENSE00001415816	12518445	12518517
ENSE00001420860	12508584	12508642
ENSE00001428986	12513299	12513360
ENSE00003549155	12473745	12473834
ENSE00003591103	12504314	12504429
ENSE00003638051	12477847	12477949
ENSE00003653431	12473913	12473983
ENSE00003655029	12496458	12496598
ENSE00003786772	12511514	12511533
ENSE00003840507	12377571	12377783

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 97.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.9649 / max 845.1085, expressed in 1456 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113144	58.4413	1455
113145	0.5236	272

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
smooth muscle tissue	UBERON:0001135	97.42	gold quality
stromal cell of endometrium	CL:0002255	97.29	gold quality
colonic epithelium	UBERON:0000397	96.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.22	gold quality
lower esophagus	UBERON:0013473	96.17	gold quality
myometrium	UBERON:0001296	95.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.88	gold quality
saphenous vein	UBERON:0007318	95.67	gold quality
mucosa of stomach	UBERON:0001199	95.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.55	gold quality
renal glomerulus	UBERON:0000074	95.53	gold quality
cauda epididymis	UBERON:0004360	95.47	gold quality
metanephric glomerulus	UBERON:0004736	95.37	gold quality
tendon of biceps brachii	UBERON:0008188	95.08	gold quality
urethra	UBERON:0000057	95.05	gold quality
body of uterus	UBERON:0009853	94.31	gold quality
seminal vesicle	UBERON:0000998	94.27	gold quality
synovial joint	UBERON:0002217	94.17	gold quality
popliteal artery	UBERON:0002250	94.17	gold quality
right coronary artery	UBERON:0001625	94.16	gold quality
tibial artery	UBERON:0007610	94.16	gold quality
aorta	UBERON:0000947	93.90	gold quality
thoracic aorta	UBERON:0001515	93.55	gold quality
sigmoid colon	UBERON:0001159	93.52	gold quality
pericardium	UBERON:0002407	93.51	gold quality
ascending aorta	UBERON:0001496	93.47	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.47	gold quality
descending thoracic aorta	UBERON:0002345	93.45	gold quality
vena cava	UBERON:0004087	93.45	gold quality
adipose tissue	UBERON:0001013	93.43	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	28.27
E-ANND-3	yes	14.75
E-HCAD-11	yes	7.10
E-CURD-112	yes	3.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

280 targeting PARVA, 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-8485	100.00	77.57	4731
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 18)

• Mammalian parvins are likely to have arisen late in evolution from gene duplication as they share a remarkably similar exon/intron organization. (PMID:11722847)
• inhibition of the ILK-alpha-parvin complex is sufficient, although not necessary, for promotion of apoptosis (PMID:15284246)
• Phosphorylation of actopaxin regulates cell spreading and migration. (PMID:15353548)
• the association between actopaxin and TESK1, which is likely regulated by phosphorylation of actopaxin, regulates TESK1 activity and subsequent cellular spreading on fibronectin (PMID:15817463)
• the alpha-parvin CH2-paxillin LD1 complex has a role in focal adhesion assembly (PMID:18508764)
• An unusual degree of binding degeneracy in the paxillin/alpha-parvin system that may facilitate the assembly of dynamic signaling complexes in the cell. (PMID:18940607)
• results also identify the integrin-linked kinase (ILK) and alpha-parvin proteins as a new molecular partner and target, respectively, of the Lnk adaptor. (PMID:22441983)
• Actopaxin phosphorylation is required for matrix degradation and cell invasion via regulation of Rho GTPase signaling. (PMID:22955285)
• beta2-adaptin is shown to bind to the focal adhesion protein actopaxin and localize to focal adhesions during cells spreading in an actopaxin dependent manner (PMID:23056266)
• alpha-parvin, beta-parvin and migfilin were expressed in tumor cells in 53%, 2%, 28% and 53% of effusions and 57%, 20%, 83% and 25% of solid lesions, respectively. (PMID:23099104)
• Actopaxin plays a role in hepatocellular carcinoma progression and metastasis, by way of regulation of cell invasiveness and motility, an epithelial-mesenchymal transition process, and chemosensitivity to cytotoxic drugs. (PMID:23504997)
• alpha-Parvin, a pseudopodial constituent, was found to promote migration of breast cancer cells and to be expressed exclusively by Invasive lobular carcinoma (PMID:24496929)
• PARVA promotes metastasis by modulating ILK signalling pathway in lung adenocarcinoma (PMID:25738875)
• alpha-pv-deficient HUVECs show reduced stable adherens junctions, decreased monolayer formation, and impaired motility, associated with reduced formation of integrin-mediated cell-extracellular matrix adhesion structures and an altered actin cytoskeleton. (PMID:25925587)
• Protein expression of alpha-Parvin increases with colorectal cancer progression. (PMID:26115385)
• edited form of miR-378a-3p preferentially binds to the 3’-UTR of the PARVA oncogene and inhibits its expression, thus preventing the progression of melanoma towards the malignant phenotype (PMID:29386624)
• A novel signaling pathway consisting of alpha-parvin, G3BP2, and TWIST1 regulates breast cancer progression and metastasis, this suggests that the activation of this signaling pathway is a key factor for driving the progression and poor clinical outcome of human ER-negative breast cancer. (PMID:30804457)
• Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics. (PMID:33587032)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	parvab	ENSDARG00000035629
danio_rerio	parvaa	ENSDARG00000043710
mus_musculus	Parva	ENSMUSG00000030770
rattus_norvegicus	Parva	ENSRNOG00000015713
drosophila_melanogaster	parvin	FBGN0052528
caenorhabditis_elegans		WBGENE00003932

Paralogs (2): PARVG (ENSG00000138964), PARVB (ENSG00000188677)

Protein

Protein identifiers

Alpha-parvin — Q9NVD7 (reviewed: Q9NVD7)

Alternative names: Actopaxin, CH-ILKBP, Calponin-like integrin-linked kinase-binding protein, Matrix-remodeling-associated protein 2

All UniProt accessions (2): E9PS97, Q9NVD7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in sarcomere organization and in smooth muscle cell contraction. Required for normal development of the embryonic cardiovascular system, and for normal septation of the heart outflow tract. Plays a role in sprouting angiogenesis and is required for normal adhesion of vascular smooth muscle cells to endothelial cells during blood vessel development. Plays a role in the reorganization of the actin cytoskeleton, formation of lamellipodia and ciliogenesis. Plays a role in the establishment of cell polarity, cell adhesion, cell spreading, and directed cell migration. Within the IPP (ILK-PINCH-PARVIN) complex, binds to F-actin, promoting F-actin bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration.

Subunit / interactions. Component of the heterotrimeric IPP (ILK-PINCH-PARVIN) complex composed of ILK, LIMS1/PINCH and PARVA; the complex binds to F-actin via the C-terminal tail of LIMS1 and the N-terminal region of PARVA, promoting F-actin filament bundling. Formation of the IPP complex is dependent on protein kinase C and precedes integrin-mediated cell adhesion and spreading. Interacts with TGFB1I1. Interacts with ARHGAP31. Interacts with the actin cytoskeleton. Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction inhibits TESK1 kinase activity. Interacts with PXN/PAXILLIN (via LD motif 4).

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

Tissue specificity. Widely expressed, with highest levels in heart, skeletal muscle, kidney and liver.

Similarity. Belongs to the parvin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NVD7-1	1	yes
Q9NVD7-2	2

RefSeq proteins (1): NP_060692* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR028433	Parvin	Family
IPR036872	CH_dom_sf	Homologous_superfamily

Pfam: PF00307

UniProt features (30 total): helix 8, modified residue 6, mutagenesis site 4, region of interest 3, splice variant 2, domain 2, initiator methionine 1, chain 1, sequence conflict 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
2VZC	X-RAY DIFFRACTION	1.05
9TP9	X-RAY DIFFRACTION	1.45
9D5E	X-RAY DIFFRACTION	1.5
9D5F	X-RAY DIFFRACTION	1.5
9D5H	X-RAY DIFFRACTION	1.5
9D5I	X-RAY DIFFRACTION	1.5
9D5P	X-RAY DIFFRACTION	1.5
9TPD	X-RAY DIFFRACTION	1.5
9D5G	X-RAY DIFFRACTION	1.55
2VZG	X-RAY DIFFRACTION	1.8
3KMU	X-RAY DIFFRACTION	1.8
3REP	X-RAY DIFFRACTION	1.8
6MIB	X-RAY DIFFRACTION	1.8
3KMW	X-RAY DIFFRACTION	2
2VZD	X-RAY DIFFRACTION	2.1
2VZI	X-RAY DIFFRACTION	2.2
9UIU	X-RAY DIFFRACTION	2.35
2K2R	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVD7-F1	80.18	0.49

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 (6): 14, 19, 28, 62, 2, 8

Mutagenesis-validated functional residues (4):

Position	Phenotype
4	loss of interaction with tesk1, however no effect on interaction with ilk; when associated with d-8.
8	loss of interaction with tesk1, however no effect on interaction with ilk; when associated with d-4.
37–42	reduced actin binding.
271	loss of interaction with ilk. loss of localization to focal adhesions.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-446343	Localization of the PINCH-ILK-PARVIN complex to focal adhesions
R-HSA-446353	Cell-extracellular matrix interactions
R-HSA-446388	Regulation of cytoskeletal remodeling and cell spreading by IPP complex components

MSigDB gene sets: 202 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GU_PDEF_TARGETS_DN, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_CELL_CHEMOTAXIS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_CELL_CELL_ADHESION, GOBP_TAXIS, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS

GO Biological Process (17): sprouting angiogenesis (GO:0002040), outflow tract septum morphogenesis (GO:0003148), establishment or maintenance of cell polarity (GO:0007163), actin cytoskeleton organization (GO:0030036), heterotypic cell-cell adhesion (GO:0034113), substrate adhesion-dependent cell spreading (GO:0034446), protein stabilization (GO:0050821), cilium assembly (GO:0060271), actin-mediated cell contraction (GO:0070252), smooth muscle cell chemotaxis (GO:0071670), establishment or maintenance of cell polarity regulating cell shape (GO:0071963), angiogenesis (GO:0001525), chemotaxis (GO:0006935), cell adhesion (GO:0007155), regulation of cell shape (GO:0008360), cell projection organization (GO:0030030), plasma membrane bounded cell projection assembly (GO:0120031)

GO Molecular Function (4): actin binding (GO:0003779), protein kinase inhibitor activity (GO:0004860), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cell-extracellular matrix interactions	2
Cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	2
angiogenesis	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
cytoskeleton organization	1
actin filament-based process	1
cell-cell adhesion	1
cell-substrate adhesion	1
regulation of protein stability	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
actin filament-based movement	1
smooth muscle cell migration	1
cell chemotaxis	1
establishment or maintenance of cell polarity	1
regulation of cell shape	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
response to chemical	1
taxis	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cellular component organization	1
cell projection assembly	1
plasma membrane bounded cell projection organization	1
cytoskeletal protein binding	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
cell adhesion molecule binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARVA	LIMS1	P48059	999
PARVA	ILK	P57043	999
PARVA	PXN	P49023	995
PARVA	VCL	P18206	947
PARVA	TLN1	Q9Y490	939
PARVA	TLN2	Q9Y4G6	939
PARVA	RSU1	Q15404	928
PARVA	LIMS2	Q7Z4I7	844
PARVA	FERMT2	Q96AC1	810
PARVA	NCK2	O43639	777
PARVA	TGFB1I1	O43294	683
PARVA	SLC36A3	Q495N2	656
PARVA	PTK2	Q05397	652
PARVA	GIT2	Q14161	650
PARVA	ARHGEF6	Q15052	645

IntAct

88 interactions, top by confidence:

A	B	Type	Score
ILK	PARVA	psi-mi:“MI:0915”(physical association)	0.970
PARVA	ILK	psi-mi:“MI:0915”(physical association)	0.970
ILK	LIMS1	psi-mi:“MI:0914”(association)	0.960
LIMS1	ILK	psi-mi:“MI:0914”(association)	0.960
RSU1	LIMS1	psi-mi:“MI:0914”(association)	0.850
MOCOS	PARVA	psi-mi:“MI:0915”(physical association)	0.800
PARVA	MOCOS	psi-mi:“MI:0915”(physical association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ILK	PXN	psi-mi:“MI:0915”(physical association)	0.670
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
PARVA	LIMS1	psi-mi:“MI:0914”(association)	0.640
ENKD1	PARVA	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	PARVA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (128): PARVA (Two-hybrid), PARVA (Two-hybrid), PARVA (Affinity Capture-MS), PARVA (Affinity Capture-MS), PARVA (Affinity Capture-MS), MOCOS (Affinity Capture-MS), PARVB (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), VPS11 (Affinity Capture-MS), GCA (Affinity Capture-MS), ILK (Affinity Capture-MS), DDX47 (Affinity Capture-MS), PARVA (Two-hybrid), PARVA (Co-fractionation), PARVA (Co-fractionation)

ESM2 similar proteins: A0JMA8, A1A535, A2AIV2, A6H8H2, A8E7C5, B7PXE3, D3ZHV2, F1REV3, O14617, O16785, O35711, O43150, O43903, O54774, P11862, P30427, Q14D04, Q5PQS3, Q5RAV3, Q5VZ89, Q61QK6, Q69YN4, Q6S5J6, Q6ZWQ0, Q6ZWR6, Q7SIG6, Q7Z3E5, Q865S1, Q8C1B1, Q8C4Q6, Q8CDA1, Q8NF91, Q8NFA0, Q91V36, Q91ZU6, Q96BJ3, Q99K01, Q9BXL7, Q9EPC1, Q9ERD8

Diamond homologs: O16785, Q1ZXH8, Q9EPC1, Q9ERD8, Q9ES46, Q9HB97, Q9HBI0, Q9HBI1, Q9NVD7, Q9VEN1, A4IF63, A5D7D1, D2GXS7, D3ZHA0, D3ZHV2, D3ZQG6, E7FAM5, F7H9X2, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O97592, P05094, P05095, P11277, P11530, P11531, P11532, P11533, P12814, P15508, P18091, P20111, P21333

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MAPK1	“up-regulates activity”	PARVA	phosphorylation
PARVA	“form complex”	“IPP complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3134 predictions. Top by Δscore:

Variant	Effect	Δscore
11:12377779:GGAGG:G	donor_gain	1.0000
11:12377780:GAGG:G	donor_gain	1.0000
11:12377780:GAGGG:G	donor_gain	1.0000
11:12377782:GG:G	donor_gain	1.0000
11:12377783:GG:G	donor_gain	1.0000
11:12377785:T:A	donor_loss	1.0000
11:12473743:A:AG	acceptor_gain	1.0000
11:12473744:G:GA	acceptor_gain	1.0000
11:12473744:GT:G	acceptor_gain	1.0000
11:12473911:A:AG	acceptor_gain	1.0000
11:12473912:G:GG	acceptor_gain	1.0000
11:12477841:CTGTA:C	acceptor_loss	1.0000
11:12477842:TGTAG:T	acceptor_loss	1.0000
11:12477843:GTA:G	acceptor_loss	1.0000
11:12477844:TA:T	acceptor_loss	1.0000
11:12477845:A:T	acceptor_loss	1.0000
11:12477959:T:G	donor_gain	1.0000
11:12496446:T:TA	acceptor_gain	1.0000
11:12496450:A:AG	acceptor_gain	1.0000
11:12496451:C:G	acceptor_gain	1.0000
11:12496453:CTCA:C	acceptor_loss	1.0000
11:12496454:TCA:T	acceptor_loss	1.0000
11:12496455:CAGAG:C	acceptor_loss	1.0000
11:12496456:A:AG	acceptor_gain	1.0000
11:12496456:A:C	acceptor_loss	1.0000
11:12496457:G:GA	acceptor_gain	1.0000
11:12496457:GA:G	acceptor_gain	1.0000
11:12496457:GAGA:G	acceptor_gain	1.0000
11:12496457:GAGAA:G	acceptor_gain	1.0000
11:12496594:GGATT:G	donor_gain	1.0000

AlphaMissense

2433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:12473976:T:C	L97P	1.000
11:12477859:T:A	W104R	1.000
11:12477859:T:C	W104R	1.000
11:12477875:T:G	L109W	1.000
11:12477887:G:C	R113T	1.000
11:12477896:T:A	V116E	1.000
11:12477913:G:C	D122H	1.000
11:12477922:G:C	D125H	1.000
11:12477923:A:C	D125A	1.000
11:12477923:A:G	D125G	1.000
11:12477923:A:T	D125V	1.000
11:12477925:G:A	G126R	1.000
11:12477925:G:C	G126R	1.000
11:12477926:G:A	G126E	1.000
11:12477926:G:T	G126V	1.000
11:12477944:T:C	L132P	1.000
11:12496516:G:C	Q153H	1.000
11:12496516:G:T	Q153H	1.000
11:12496527:T:C	L157P	1.000
11:12496536:T:A	V160D	1.000
11:12496539:T:C	L161P	1.000
11:12496586:T:A	W177R	1.000
11:12496586:T:C	W177R	1.000
11:12504317:T:A	V182D	1.000
11:12513304:G:C	D248H	1.000
11:12513310:T:C	F250L	1.000
11:12513311:T:C	F250S	1.000
11:12513311:T:G	F250C	1.000
11:12513312:T:A	F250L	1.000
11:12513312:T:G	F250L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007411 (11:12406959 C>T), RS1000037270 (11:12518086 G>A), RS1000058440 (11:12499261 C>T), RS1000097388 (11:12503001 T>C), RS1000106818 (11:12456127 C>T), RS1000129265 (11:12462679 C>T), RS1000146510 (11:12406817 C>G,T), RS1000160296 (11:12462988 C>T), RS1000163499 (11:12387529 T>G), RS1000176748 (11:12380965 T>C), RS1000183545 (11:12432257 G>A,C), RS1000190294 (11:12425741 A>C,G), RS1000208111 (11:12380676 G>A,C,T), RS1000237877 (11:12509684 C>T), RS1000250668 (11:12515223 C>T)

Disease associations

OMIM: gene MIM:608120 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000661_8	Mortality in heart failure	7.000000e-06
GCST002755_4	Depressive symptoms (SSRI exposure interaction)	8.000000e-07
GCST002875_36	Diisocyanate-induced asthma	2.000000e-06
GCST004735_9	Epstein-Barr virus copy number in lymphoblastoid cell lines	6.000000e-06
GCST004744_51	Lung adenocarcinoma	3.000000e-06
GCST010724_20	HOMA-B (corrected for HOMA-IR)	5.000000e-08
GCST012116_3	Rheumatic heart disease	3.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0007006	depressive symptom measurement
EFO:0007010	drug use measurement
EFO:0007011	SSRI use measurement
EFO:0006995	response to diisocyanate
EFO:0004469	HOMA-B

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
sodium arsenite	decreases expression, increases expression, increases stability	3
bisphenol A	decreases expression, decreases methylation	2
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, increases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases methylation	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1

Clinical trials (associated diseases)

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