PARVB

Summary

PARVB (parvin beta, HGNC:14653) is a protein-coding gene on chromosome 22q13.31, encoding Beta-parvin (Q9HBI1). Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6.

This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 29780 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_013327

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14653
Approved symbol	PARVB
Name	parvin beta
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	CGI-56
Ensembl gene	ENSG00000188677
Ensembl biotype	protein_coding
OMIM	608121
Entrez	29780

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000338758, ENST00000402876, ENST00000404989, ENST00000406477, ENST00000444029, ENST00000477438, ENST00000477795, ENST00000484345, ENST00000495824, ENST00000619710

RefSeq mRNA: 4 — MANE Select: NM_013327 NM_001003828, NM_001243385, NM_001243386, NM_013327

CCDS: CCDS14056, CCDS46724, CCDS58808, CCDS74874

Canonical transcript exons

ENST00000338758 — 13 exons

Exon	Start	End
ENSE00001369466	44131487	44131627
ENSE00001619032	44151483	44151551
ENSE00001694882	44140124	44140143
ENSE00001738801	44157982	44158083
ENSE00001774993	44136460	44136518
ENSE00001797593	44147861	44147922
ENSE00001916829	44024302	44024451
ENSE00001952025	44168602	44172939
ENSE00002182433	44132894	44133009
ENSE00003513902	44163858	44163930
ENSE00003703499	44119038	44119140
ENSE00003705159	44100053	44100123
ENSE00003707472	44093928	44094017

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.7428 / max 398.8839, expressed in 1752 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192635	27.0738	1744
192636	1.5415	832
192646	1.2498	166
192632	0.3935	139
192633	0.3584	166
209496	0.2571	137
192634	0.2041	85
192642	0.1296	26
192645	0.1235	63
192637	0.1166	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.72	gold quality
gastrocnemius	UBERON:0001388	97.71	gold quality
muscle of leg	UBERON:0001383	97.28	gold quality
apex of heart	UBERON:0002098	95.85	gold quality
muscle organ	UBERON:0001630	95.09	gold quality
monocyte	CL:0000576	95.07	gold quality
heart left ventricle	UBERON:0002084	94.98	gold quality
right atrium auricular region	UBERON:0006631	94.72	gold quality
mononuclear cell	CL:0000842	94.63	gold quality
cardiac ventricle	UBERON:0002082	94.43	gold quality
leukocyte	CL:0000738	94.29	gold quality
omental fat pad	UBERON:0010414	94.13	gold quality
peritoneum	UBERON:0002358	94.05	gold quality
cardiac atrium	UBERON:0002081	93.28	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.12	gold quality
heart	UBERON:0000948	92.32	gold quality
islet of Langerhans	UBERON:0000006	92.03	gold quality
right lung	UBERON:0002167	91.87	gold quality
right adrenal gland	UBERON:0001233	91.67	gold quality
upper lobe of left lung	UBERON:0008952	91.62	gold quality
left adrenal gland	UBERON:0001234	91.54	gold quality
right adrenal gland cortex	UBERON:0035827	91.44	gold quality
left adrenal gland cortex	UBERON:0035825	91.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.09	gold quality
lower esophagus	UBERON:0013473	91.03	gold quality
right ovary	UBERON:0002118	90.92	gold quality
sural nerve	UBERON:0015488	90.91	gold quality
granulocyte	CL:0000094	90.90	gold quality
skeletal muscle tissue	UBERON:0001134	90.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.69	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	36.16
E-HCAD-4	yes	35.12
E-CURD-122	yes	19.71
E-CURD-119	yes	16.83
E-HCAD-10	yes	16.47
E-MTAB-9221	yes	15.86
E-MTAB-5061	yes	10.27
E-MTAB-7303	no	494.48
E-GEOD-81547	no	10.34
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMAD1

miRNA regulators (miRDB)

27 targeting PARVB, 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-4500	99.99	72.72	2367
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646
HSA-MIR-3130-3P	94.98	66.97	574

Literature-anchored findings (GeneRIF, showing 22)

• Mammalian parvins are likely to have arisen late in evolution from gene duplication as they share a remarkably similar exon/intron organization. (PMID:11722847)
• the ILK-affixin complex has a role in integrin-cytoskeleton linkage during platelet aggregation [affixin] (PMID:12372433)
• affixin provide a novel signalling pathway that links integrin signalling to Cdc42/Rac1 activation. (PMID:15005707)
• ILK-affixin complex serves as an integrin-anchoring site for alpha-actinin and thereby mediates integrin signaling to alpha-actinin, which has been shown to play a critical role in actin polymerization at focal adhesions. (PMID:15159419)
• alpha- and beta-parvins play distinct roles in Rac activation or lamellipodium formation and protection of cells from apoptosis. (PMID:15284246)
• loss of ParvB expression is a novel mechanism for upregulating ILK activity in tumors (PMID:15467740)
• Data show that affixin is a dysferlin binding protein that colocalizes with dysferlin at the sarcolemma of normal skeletal muscle. (PMID:15835269)
• Parvin-beta might influence breast cancer progression (PMID:17998334)
• results suggest that affixin is involved in reorganization of subsarcolemmal cytoskeletal actin by activation of Rac1 through alpha and betaPIXs in skeletal muscle (PMID:18325335)
• Data from functional molecular imaging demonstrated that beta-parvin plays a regulatory role in the ILK-mediated Akt (also called protein kinase B) signaling cascades, suggesting that beta-parvin might be a crucial modulator of cell survival. (PMID:20164304)
• Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication. (PMID:20345489)
• downexpression of ParvB level in urothelial cell carcinoma of the upper urinary tract (UUT-UC) correlated with tumour stage, and was an independent unfavourable prognostic factor for disease-specific survival of patients with UUT-UC (PMID:20736946)
• proper localization of beta-parvin to focal adhesions requires both the paxillin and integrin-linked kinase binding sites and that paxillin is important for early targeting of beta-parvin. (PMID:22869380)
• 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)
• Polymorphisms in the SAMM50 and PARVB genes in addition to those in the PNPLA3 gene were observed to be associated with the development and progression of NAFLD. (PMID:23535911)
• PARVB plays a potential role in the pathogenesis of coronary restenosis. (PMID:23950981)
• Our results suggested that variations, including insertion/deletions, in PARVB, as well as those in PNPLA3, are important in the progression of NAFLD. (PMID:24621583)
• PARVB overexpression is a candidate biomarker for endophytic tumours and metastasis. (PMID:25422907)
• Targeted-bisulfite sequence analysis of the methylation of CpG islands in genes encoding PNPLA3, SAMM50, and PARVB of patients with non-alcoholic fatty liver disease. (PMID:25776890)
• Protein expression of beta-Parvin increases with colorectal cancer progression. (PMID:26115385)
• study found polymorphisms of rs5764455 and rs6006473 in PARVB gene in the Han Chinese population, and these polymorphisms were associated with the occurrence and progression of NAFLD. (PMID:26343796)
• Taken together, our results indicate that 24-MCF treatment increases parvin-beta expression, which may inhibit ILK downstream signaling. (PMID:26549231)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	parvb	ENSDARG00000019117
mus_musculus	Parvb	ENSMUSG00000022438
rattus_norvegicus	Parvb	ENSRNOG00000055305
drosophila_melanogaster	parvin	FBGN0052528
caenorhabditis_elegans		WBGENE00003932

Paralogs (2): PARVG (ENSG00000138964), PARVA (ENSG00000197702)

Protein

Protein identifiers

Beta-parvin — Q9HBI1 (reviewed: Q9HBI1)

Alternative names: Affixin

All UniProt accessions (3): A0A087WZB5, B0QYP8, Q9HBI1

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6. Is involved in the reorganization of the actin cytoskeleton and formation of lamellipodia. Plays a role in cell adhesion, cell spreading, establishment or maintenance of cell polarity, and cell migration.

Subunit / interactions. Interacts with DYSF. Interacts with ILK, ARHGEF6, PXN (via LD motifs), ACTN2 and actin.

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

Tissue specificity. Expressed predominantly in heart and skeletal muscle.

Similarity. Belongs to the parvin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HBI1-1	1	yes
Q9HBI1-2	2
Q9HBI1-3	3

RefSeq proteins (4): NP_001003828, NP_001230314, NP_001230315, NP_037459* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00307

UniProt features (29 total): helix 9, sequence conflict 6, domain 2, sequence variant 2, mutagenesis site 2, modified residue 2, splice variant 2, chain 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4EDM	X-RAY DIFFRACTION	2
4EDL	X-RAY DIFFRACTION	2.1
4EDN	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBI1-F1	82.03	0.54

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 (2): 7, 54

Mutagenesis-validated functional residues (2):

Position	Phenotype
256	abolishes interaction with pxn.
299	abolishes interaction with ilk. abolishes location at focal adhesion sites.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-446353	Cell-extracellular matrix interactions
R-HSA-446388	Regulation of cytoskeletal remodeling and cell spreading by IPP complex components

MSigDB gene sets: 143 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, KAAB_FAILED_HEART_ATRIUM_DN, DOANE_BREAST_CANCER_CLASSES_DN, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_LAMELLIPODIUM_ORGANIZATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, GOMF_ACTIN_BINDING, GOBP_CELL_PROJECTION_ORGANIZATION, YAMAZAKI_TCEB3_TARGETS_UP, GOBP_CELL_SUBSTRATE_ADHESION

GO Biological Process (7): cell projection assembly (GO:0030031), lamellipodium assembly (GO:0030032), actin cytoskeleton organization (GO:0030036), substrate adhesion-dependent cell spreading (GO:0034446), establishment or maintenance of cell polarity regulating cell shape (GO:0071963), cell adhesion (GO:0007155), plasma membrane bounded cell projection assembly (GO:0120031)

GO Molecular Function (2): actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (12): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), lamellipodium (GO:0030027), cytoskeleton (GO:0005856), membrane (GO:0016020), sarcomere (GO:0030017), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cellular component assembly	1
cell projection organization	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
cytoskeleton organization	1
actin filament-based process	1
cell-substrate adhesion	1
establishment or maintenance of cell polarity	1
regulation of cell shape	1
cellular process	1
cell projection assembly	1
plasma membrane bounded cell projection organization	1
cytoskeletal protein binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cell-substrate junction	1
cytoskeleton	1
I band	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular membraneless organelle	1
myofibril	1
cell junction	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARVB	ILK	P57043	999
PARVB	LIMS1	P48059	998
PARVB	ARHGEF6	Q15052	993
PARVB	PXN	P49023	965
PARVB	TLN2	Q9Y4G6	911
PARVB	TLN1	Q9Y490	910
PARVB	RSU1	Q15404	881
PARVB	VCL	P18206	859
PARVB	CAPN3	P20807	801
PARVB	CDC42	P21181	737
PARVB	MIOX	Q9UGB7	720
PARVB	CAV3	P56539	686
PARVB	AHNAK	Q09666	677
PARVB	LIMS2	Q7Z4I7	675
PARVB	ADM2	Q7Z4H4	672

IntAct

46 interactions, top by confidence:

A	B	Type	Score
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
PARVB	Arhgef7	psi-mi:“MI:0403”(colocalization)	0.620
PARVB	Arhgef7	psi-mi:“MI:0915”(physical association)	0.620
Arhgef7	PARVB	psi-mi:“MI:0915”(physical association)	0.620
PARVB	Arhgef7	psi-mi:“MI:0407”(direct interaction)	0.620
LIMS1	TYMS	psi-mi:“MI:0914”(association)	0.530
ILK	HSPA8	psi-mi:“MI:0914”(association)	0.530
PARVA	CCNB1	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
PARVB	Arhgef6	psi-mi:“MI:0403”(colocalization)	0.460
PARVB	Arhgef6	psi-mi:“MI:0915”(physical association)	0.460
Arhgef6	PARVB	psi-mi:“MI:0915”(physical association)	0.460
PARVB	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.400
PARVB	STK4	psi-mi:“MI:0915”(physical association)	0.370
ILK	ELOC	psi-mi:“MI:0914”(association)	0.350
HMGN2	NSD2	psi-mi:“MI:0914”(association)	0.350
RSU1	ICAM2	psi-mi:“MI:0914”(association)	0.350
ILK	PGAM2	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Co-fractionation), PARVB (Co-fractionation), PFKFB2 (Co-fractionation), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-MS), PARVB (Affinity Capture-RNA), PARVB (Affinity Capture-MS)

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

SIGNOR signaling

1 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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
Cell-extracellular matrix interactions	5	120.0×	8e-08
mRNA Splicing - Major Pathway	5	9.8×	4e-03
Dengue Virus-Host Interactions	5	8.2×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	5	14.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3041 predictions. Top by Δscore:

Variant	Effect	Δscore
22:44024432:G:GT	donor_gain	1.0000
22:44024450:GG:G	donor_gain	1.0000
22:44024451:GG:G	donor_gain	1.0000
22:44093918:T:TA	acceptor_gain	1.0000
22:44093923:A:AG	acceptor_gain	1.0000
22:44093925:CAGT:C	acceptor_loss	1.0000
22:44093925:CAGTG:C	acceptor_gain	1.0000
22:44093926:A:AG	acceptor_gain	1.0000
22:44093926:A:G	acceptor_loss	1.0000
22:44093926:AGT:A	acceptor_gain	1.0000
22:44093926:AGTGA:A	acceptor_gain	1.0000
22:44093927:G:GT	acceptor_gain	1.0000
22:44093927:GT:G	acceptor_gain	1.0000
22:44093927:GTG:G	acceptor_gain	1.0000
22:44093927:GTGA:G	acceptor_gain	1.0000
22:44093927:GTGAG:G	acceptor_gain	1.0000
22:44094013:GCTTG:G	donor_gain	1.0000
22:44094014:C:G	donor_gain	1.0000
22:44094018:G:C	donor_loss	1.0000
22:44094018:G:GG	donor_gain	1.0000
22:44094019:T:G	donor_loss	1.0000
22:44094053:T:G	donor_gain	1.0000
22:44100047:T:TA	acceptor_gain	1.0000
22:44100051:A:AG	acceptor_gain	1.0000
22:44100052:G:GG	acceptor_gain	1.0000
22:44100052:GA:G	acceptor_gain	1.0000
22:44100120:CAAGG:C	donor_loss	1.0000
22:44100121:AAGG:A	donor_loss	1.0000
22:44100122:AGGTA:A	donor_loss	1.0000
22:44100123:GGTA:G	donor_loss	1.0000

AlphaMissense

2381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:44147882:T:A	L245Q	1.000
22:44151487:T:C	L260P	1.000
22:44151495:T:C	F263L	1.000
22:44151497:T:A	F263L	1.000
22:44151497:T:G	F263L	1.000
22:44151511:T:C	L268P	1.000
22:44157991:G:C	G285R	1.000
22:44157992:G:A	G285D	1.000
22:44157992:G:T	G285V	1.000
22:44168635:G:T	R351M	1.000
22:44119117:G:A	G118D	0.999
22:44131556:T:C	L149P	0.999
22:44147866:G:C	D240H	0.999
22:44147867:A:C	D240A	0.999
22:44147867:A:T	D240V	0.999
22:44147872:T:C	F242L	0.999
22:44147873:T:C	F242S	0.999
22:44147873:T:G	F242C	0.999
22:44147874:C:A	F242L	0.999
22:44147874:C:G	F242L	0.999
22:44147876:A:T	D243V	0.999
22:44147882:T:C	L245P	0.999
22:44147906:T:C	L253P	0.999
22:44151487:T:A	L260H	0.999
22:44151496:T:C	F263S	0.999
22:44157991:G:T	G285C	0.999
22:44158007:T:C	L290P	0.999
22:44158010:T:C	L291P	0.999
22:44158015:G:C	G293R	0.999
22:44158016:G:A	G293D	0.999

dbSNP variants (sampled 300 via entrez): RS1000027483 (22:44097959 C>T), RS1000039364 (22:44027173 G>C), RS1000066302 (22:44171451 T>C,G), RS1000109619 (22:44101438 T>A,G), RS1000115794 (22:44149435 C>A,G), RS1000127948 (22:44124829 G>A), RS1000137112 (22:44138363 G>A,C), RS1000139718 (22:44032385 C>T), RS1000145977 (22:44169660 C>A,T), RS1000147856 (22:44075816 C>A,T), RS1000148384 (22:44068549 C>T), RS1000169519 (22:44089963 T>C), RS1000175847 (22:44118371 G>A), RS1000182908 (22:44069309 G>A), RS1000188515 (22:44083714 A>T)

Disease associations

OMIM: gene MIM:608121 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000583_15	Hematological and biochemical traits	2.000000e-12
GCST000583_18	Hematological and biochemical traits	2.000000e-12
GCST001576_4	Nonalcoholic fatty liver disease	8.000000e-07
GCST001915_43	Alzheimer’s disease (cognitive decline)	5.000000e-07
GCST001928_4	Pediatric non-alcoholic fatty liver disease activity score	2.000000e-20
GCST002566_2	Response to chemotherapy in breast cancer hypertensive cases (cumulative dose) (bevacizumab)	4.000000e-07
GCST002567_2	Response to chemotherapy in breast cancer (hypertension) (bevacizumab)	4.000000e-06
GCST002591_10	Lewy body disease	7.000000e-06
GCST005552_3	Systemic sclerosis (anti-centromere-positive)	8.000000e-07
GCST90002393_594	Monocyte count	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0005944	cumulative dose response to bevacizumab
EFO:0005943	response to bevacizumab
EFO:0006799	Lewy body dementia measurement
EFO:0008536	anti-centromere-antibody-positive systemic scleroderma
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Smoke	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
belinostat	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	decreases methylation	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Formaldehyde	decreases expression	1
Lovastatin	decreases response to substance	1
Methyl Methanesulfonate	decreases expression	1
Selenomethionine	affects expression	1
Vanadates	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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