PDLIM2

Summary

PDLIM2 (PDZ and LIM domain 2, HGNC:13992) is a protein-coding gene on chromosome 8p21.3, encoding PDZ and LIM domain protein 2 (Q96JY6). Probable adapter protein located at the actin cytoskeleton that promotes cell attachment.

This gene encodes a member of the ALP subfamily of PDZ-LIM domain proteins. The encoded protein suppresses anchorage-dependent growth and promotes cell migration and adhesion through interactions with the actin cytoskeleton via the PDZ domain. The encoded protein is also a putative tumor suppressor protein, and decreased expression of this gene is associated with several malignancies including breast cancer and adult T-cell leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 64236 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 154 total
• MANE Select transcript: NM_001368120

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13992
Approved symbol	PDLIM2
Name	PDZ and LIM domain 2
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000120913
Ensembl biotype	protein_coding
OMIM	609722
Entrez	64236

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 21 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000265810, ENST00000308354, ENST00000339162, ENST00000397760, ENST00000397761, ENST00000409141, ENST00000409417, ENST00000416159, ENST00000426493, ENST00000429812, ENST00000436754, ENST00000443561, ENST00000448520, ENST00000452226, ENST00000456545, ENST00000464275, ENST00000491330, ENST00000614502, ENST00000616289, ENST00000622226, ENST00000884623, ENST00000884624, ENST00000884625, ENST00000884626, ENST00000884627

RefSeq mRNA: 4 — MANE Select: NM_001368120 NM_001368120, NM_021630, NM_176871, NM_198042

CCDS: CCDS34860, CCDS34861, CCDS6032, CCDS94264

Canonical transcript exons

ENST00000409417 — 9 exons

Exon	Start	End
ENSE00003485597	22589298	22589374
ENSE00003537302	22584821	22584890
ENSE00003626335	22581379	22581530
ENSE00003648215	22593733	22594298
ENSE00003675409	22591551	22591668
ENSE00003789317	22585321	22585399
ENSE00003789968	22589596	22589741
ENSE00003791641	22585017	22585162
ENSE00003978173	22580475	22580697

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.3489 / max 403.4485, expressed in 1739 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87831	39.8585	1372
87820	10.0673	1317
87823	0.9570	258
87825	0.6329	209
87824	0.4734	197
87822	0.4666	118
205113	0.2367	126
87829	0.1770	72
87830	0.1281	56
87818	0.0788	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	98.66	gold quality
pharyngeal mucosa	UBERON:0000355	98.28	gold quality
lower esophagus mucosa	UBERON:0035834	98.03	gold quality
skin of leg	UBERON:0001511	98.00	gold quality
ascending aorta	UBERON:0001496	97.70	gold quality
thoracic aorta	UBERON:0001515	97.69	gold quality
skin of abdomen	UBERON:0001416	97.68	gold quality
descending thoracic aorta	UBERON:0002345	97.59	gold quality
right coronary artery	UBERON:0001625	97.53	gold quality
stromal cell of endometrium	CL:0002255	97.35	gold quality
nipple	UBERON:0002030	97.33	gold quality
tibial nerve	UBERON:0001323	97.18	gold quality
aorta	UBERON:0000947	97.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.98	gold quality
upper lobe of left lung	UBERON:0008952	96.96	gold quality
popliteal artery	UBERON:0002250	96.82	gold quality
tibial artery	UBERON:0007610	96.82	gold quality
upper lobe of lung	UBERON:0008948	96.61	gold quality
granulocyte	CL:0000094	96.55	gold quality
zone of skin	UBERON:0000014	96.52	gold quality
esophagus mucosa	UBERON:0002469	96.50	gold quality
left coronary artery	UBERON:0001626	96.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.41	gold quality
gastrocnemius	UBERON:0001388	96.37	gold quality
ectocervix	UBERON:0012249	96.37	gold quality
cerebellar hemisphere	UBERON:0002245	96.34	gold quality
saphenous vein	UBERON:0007318	96.29	gold quality
coronary artery	UBERON:0001621	96.26	gold quality
cerebellar cortex	UBERON:0002129	96.22	gold quality
esophagus	UBERON:0001043	96.20	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	5399.90
E-MTAB-6701	yes	37.06
E-HCAD-10	yes	28.41
E-HCAD-13	yes	25.96
E-MTAB-9388	yes	10.43
E-ANND-3	yes	10.36
E-CURD-112	yes	4.18
E-MTAB-6379	no	332.01

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 27)

• Knockdown of Mystique 2 with small interfering RNA abrogated both adhesion and migration in MCF10A and MCF-7 cells (PMID:15659642)
• PDLIM2 deficiency resulted in larger amounts of nuclear p65, defective p65 ubiquitination and augmented production of proinflammatory cytokines in response to innate stimuli (PMID:17468759)
• Suppression of PDLIM2 expression resulted in decreased cell adhesion, increased NF-kappaB transcription reporter activity, and increased LPS-induced TNF-alpha production. (PMID:19052146)
• Data show that the PDLIM2 repression was independent of the viral regulatory protein Tax because neither short-term induction nor long-term stable expression of Tax could downregulate PDLIM2 expression. (PMID:19794962)
• PDLIM2, an essential terminator of NF-kappaB activation, is repressed in both estrogen receptor-positive and estrogen receptor-negative breast cancer cells, suggesting one important mechanism for the constitutive activation of NF-kappaB. (PMID:20185823)
• PDLIM2 binds to Tax directly, which was mediated by a putative alpa-helix motif of PDLIM2 at amino acids 236-254. (PMID:20838382)
• Pdlim2 is a novel actin-regulating protein of podocyte foot processes that may have a role in the pathogenesis of glomerular diseases. (PMID:21814175)
• PDLIM2 was a direct target gene of 1,25(OH)2D3 (PMID:23584482)
• PDLIM2 integrates cytoskeleton signaling with gene expression in epithelial differentiation by controlling the stability of key transcription factors and COP9 signalosome activity. (PMID:24196835)
• PDLIM2 expression is essential for feedback regulation of the beta1-integrin-RhoA signalling axis and integration of cellular microenvironment signals with gene expression to control the polarity of breast epithelial acini structures. (PMID:24863845)
• epigenetic repression of PDLIM2 can be reversed by 5-aza-2-deoxycytidine and vitamin D to suppress KSHV-associated cancer cell growth (PMID:25681443)
• The suppression of PDLIM2 expression significantly reduced cell proliferation, cell growth and neoplasm invasiveness in prostate cancer cells. (PMID:26499308)
• PDLIM2 is epigenetically repressed in ovarian cancer development and inhibition of PDLIM2 promoted ovarian cancer growth both in vivo and in vitro via NOS2-derived nitric oxide signaling, leading to recruitment of M2 type macrophages. (PMID:26593252)
• Data indicate that OR3A4 upregulation contributes to metastasis and tumorigenesis in gastric cancer by regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. (PMID:26863570)
• We conclude that inactivation of PDLIM2 is a recurrent finding in cHL and ALCL, promotes activation of inflammatory signaling pathways and thereby contributes to their pathogenesis (PMID:27538486)
• Data show that shRNA mediated knockdown of PDZ and LIM domain protein 2 (PDLIM2) in both primary meningioma and schwannoma leads to significant reductions in cellular proliferation. (PMID:28126595)
• The results showed that (i) the use of SPR chip led to comparable data compared to on-column streptavidin beads, (ii) gravity flow and microflow in wash and elution steps provided better results than centrifugation, and (iii) type and concentration of detergent did not significantly affect the interactome data of cancer-associated PDLIM2. (PMID:30194080)
• study shows that PDLIM2 expression defines a subset of triple-negative breast cancer that may benefit from targeting the beta-catenin and adhesion signaling pathways (PMID:30885980)
• Systematic profiling identifies PDLIM2 as a novel prognostic predictor for oesophageal squamous cell carcinoma (ESCC). (PMID:31222932)
• Compared to normal lung tissues, the expression of PDLIM2 was significantly decreased in human lung cancers. (PMID:31757943)
• PDLIM2 acts as a cancer suppressor gene in non-small cell lung cancer via the down regulation of NF-kappaB signaling. (PMID:32621848)
• Central Nervous System-Infecting Pathogens Escherichia coli and Cryptococcus neoformans Exploit the Host Pdlim2 for Intracellular Traversal and Exocytosis in the Blood-Brain Barrier. (PMID:34228504)
• Kruppel like factor 10 up-regulates PDZ and LIM domain containing protein 2 via nuclear factor kappa-B pathway to inhibit proliferation and inflammatory of fibroblastoid synovial cell in rheumatoid arthritis. (PMID:34713769)
• Systematic evaluation of the prognostic and immunological role of PDLIM2 across 33 cancer types. (PMID:35121770)
• High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration. (PMID:35707002)
• PDLIM2 can inactivate the TGF-beta/Smad pathway to inhibit the malignant behavior of ovarian cancer cells. (PMID:37170668)
• Tumor promoting effect of PDLIM2 downregulation involves mitochondrial ROS, oncometabolite accumulations and HIF-1alpha activation. (PMID:38880883)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdlim2	ENSDARG00000069956
mus_musculus	Pdlim2	ENSMUSG00000022090
rattus_norvegicus	Pdlim2	ENSRNOG00000008543
drosophila_melanogaster	Zasp52	FBGN0265991
caenorhabditis_elegans		WBGENE00001132

Paralogs (7): PDLIM1 (ENSG00000107438), LDB3 (ENSG00000122367), PDLIM4 (ENSG00000131435), PDLIM3 (ENSG00000154553), PDLIM5 (ENSG00000163110), PDLIM7 (ENSG00000196923), PRICKLE4 (ENSG00000278224)

Protein

Protein identifiers

PDZ and LIM domain protein 2 — Q96JY6 (reviewed: Q96JY6)

Alternative names: PDZ-LIM protein mystique

All UniProt accessions (11): A0A087WU48, A0A087WUQ1, A0A087WXJ0, B3KPU0, C9J0X3, C9J760, C9JS55, C9JSR2, C9K0F0, Q96JY6, F8WFB8

UniProt curated annotations — full annotation on UniProt →

Function. Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity.

Subunit / interactions. Interacts with alpha-actinins ACTN1 and ACTN4, FLNA and MYH9. Interacts (via LIM zinc-binding domain) with MKRN2.

Subcellular location. Cytoplasm. Nucleus Cytoplasm. Cytoskeleton Cytoplasm. Cytoskeleton Nucleus.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96JY6-1	1, Mystique 2	yes
Q96JY6-2	2
Q96JY6-3	3, Mystique 1
Q96JY6-4	4, Mystique 3
Q96JY6-5	5

RefSeq proteins (4): NP_001355049, NP_067643, NP_789847, NP_932159 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR001781	Znf_LIM	Domain
IPR031847	PDLI1-4/Zasp-like_mid	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR050604	PDZ-LIM_domain	Family

Pfam: PF00412, PF00595, PF15936

UniProt features (42 total): modified residue 12, strand 8, splice variant 5, mutagenesis site 3, sequence conflict 3, region of interest 3, helix 3, domain 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2PA1	X-RAY DIFFRACTION	1.7
3PDV	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JY6-F1	69.10	0.35

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 (12): 127, 129, 134, 137, 143, 161, 197, 203, 213, 266, 124, 126

Mutagenesis-validated functional residues (3):

Position	Phenotype
80	abolishes cell adhesion to collagen and ability to suppress anchorage independent growth.
313	abolishes ability to suppress anchorage independent growth but not cell adhesion to collagen; when associated with s-316
316	abolishes ability to suppress anchorage independent growth but not cell adhesion to collagen; when associated with s-313

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 227 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, RNGTGGGC_UNKNOWN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GGCNKCCATNK_UNKNOWN, MODULE_205, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, chr8p21, BLALOCK_ALZHEIMERS_DISEASE_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, TGANTCA_AP1_C, MARSON_FOXP3_TARGETS_UP, PU1_Q6, RYTTCCTG_ETS2_B

GO Biological Process (4): heart development (GO:0007507), actin cytoskeleton organization (GO:0030036), protein catabolic process (GO:0030163), muscle structure development (GO:0061061)

GO Molecular Function (5): actin binding (GO:0003779), ubiquitin protein ligase binding (GO:0031625), metal ion binding (GO:0046872), muscle alpha-actinin binding (GO:0051371), protein binding (GO:0005515)

GO Cellular Component (7): stress fiber (GO:0001725), nucleus (GO:0005634), adherens junction (GO:0005912), Z disc (GO:0030018), filamentous actin (GO:0031941), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
animal organ development	1
circulatory system development	1
cytoskeleton organization	1
actin filament-based process	1
macromolecule catabolic process	1
protein metabolic process	1
anatomical structure development	1
cytoskeletal protein binding	1
ubiquitin-like protein ligase binding	1
cation binding	1
alpha-actinin binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
cell-cell junction	1
I band	1
actin filament	1
protein-containing complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDLIM2	ACTN4	O43707	794
PDLIM2	ACTN1	P12814	759
PDLIM2	LIMD2	Q9BT23	680
PDLIM2	COMMD1	Q8N668	587
PDLIM2	FLNA	P21333	578
PDLIM2	MYH9	P35579	571
PDLIM2	MYO6	Q9UM54	550
PDLIM2	SCRIB	Q14160	535
PDLIM2	AMOTL1	Q8IY63	532
PDLIM2	WTIP	A6NIX2	527
PDLIM2	AJUBA	Q96IF1	525
PDLIM2	LIMD1	Q9UGP4	522
PDLIM2	HBZ	P02008	500
PDLIM2	PDLIM7	Q9NR12	493
PDLIM2	A0A0A0MSP3	A0A0A0MSP3	488
PDLIM2	TOR4A	Q9NXH8	488

IntAct

187 interactions, top by confidence:

A	B	Type	Score
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
ZNF695	PDLIM2	psi-mi:“MI:0915”(physical association)	0.560
ACD	PDLIM2	psi-mi:“MI:0915”(physical association)	0.510
rep	ACTN4	psi-mi:“MI:0914”(association)	0.480
PDLIM2	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	PDLIM2	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
CARD11	PDLIM2	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	CASK	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
WHRN	PDLIM2	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
DLG5	PDLIM2	psi-mi:“MI:0407”(direct interaction)	0.440
PDLIM2	DVL3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (30): UBE2E2 (Reconstituted Complex), PDLIM2 (Biochemical Activity), STAT4 (Affinity Capture-Western), PDLIM2 (Two-hybrid), PDLIM2 (Two-hybrid), PDLIM2 (Two-hybrid), PDLIM2 (Two-hybrid), PDLIM2 (Two-hybrid), PDLIM2 (Two-hybrid), PDLIM2 (Two-hybrid), PDLIM2 (Two-hybrid), MKRN2 (Two-hybrid), PDLIM2 (Affinity Capture-Western), PDLIM2 (Affinity Capture-MS), ZNF695 (Two-hybrid)

ESM2 similar proteins: A2A9T0, A4D2P6, A6NIX2, A7MCY6, D3Z9H7, F5GYI3, O43281, O43559, O70142, O95153, O97581, P98077, Q07912, Q148E7, Q148V8, Q15654, Q15942, Q1JQB5, Q3SX26, Q3T0C8, Q494U1, Q4KLY2, Q5REN1, Q5TM48, Q62523, Q63767, Q64355, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZRV2, Q6ZVH7, Q71FD7, Q75VX8, Q7TNF8, Q7TQJ8, Q8BG80, Q8BNN1, Q8C0R7

Diamond homologs: A1Z9P3, A1ZA47, A2ALU4, A8E0R9, D4A702, E9Q9W7, O00151, O14910, O70209, O70400, O75112, O88952, P36202, P50479, P52944, P70271, P97879, Q01613, Q09JY9, Q0P5E6, Q0P5F3, Q13424, Q13796, Q27IV2, Q28626, Q2M3G4, Q32LM6, Q3SYZ8, Q3T005, Q3T0C8, Q53GG5, Q5E9E1, Q5F425, Q5RAA5, Q5RBI7, Q5SX79, Q61234, Q62920, Q66HS7, Q6AYD6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PDLIM2	“down-regulates quantity by destabilization”	RELA	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
Ras activation upon Ca2+ influx through NMDA receptor	5	29.7×	5e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	28.3×	5e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	28.3×	5e-05
Assembly and cell surface presentation of NMDA receptors	10	26.4×	6e-10
Dopamine Neurotransmitter Release Cycle	5	25.9×	7e-05
Long-term potentiation	5	24.8×	8e-05
Neurexins and neuroligins	11	22.6×	6e-10
Protein-protein interactions at synapses	7	19.4×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	49.2×	1e-13
protein localization to synapse	6	35.4×	3e-06
receptor clustering	7	33.6×	6e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	26.7×	2e-06
bicellular tight junction assembly	5	12.7×	3e-03
protein-containing complex assembly	11	9.6×	4e-06
cell-cell adhesion	10	7.8×	8e-05
regulation of small GTPase mediated signal transduction	7	7.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1891 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22580598:CTCA:C	acceptor_loss	1.0000
8:22580599:TCA:T	acceptor_loss	1.0000
8:22580600:CAGGT:C	acceptor_loss	1.0000
8:22580601:AGGTA:A	acceptor_loss	1.0000
8:22580602:GGT:G	acceptor_gain	1.0000
8:22580694:TAAGG:T	donor_loss	1.0000
8:22580696:AGGTA:A	donor_loss	1.0000
8:22581373:CTACA:C	acceptor_loss	1.0000
8:22581374:TACA:T	acceptor_loss	1.0000
8:22581376:CA:C	acceptor_loss	1.0000
8:22581377:A:AG	acceptor_gain	1.0000
8:22581378:G:GG	acceptor_gain	1.0000
8:22581526:GACCG:G	donor_gain	1.0000
8:22581527:ACCGG:A	donor_loss	1.0000
8:22581528:CCGGT:C	donor_loss	1.0000
8:22581529:CGG:C	donor_loss	1.0000
8:22581530:GGTAG:G	donor_loss	1.0000
8:22581531:G:GG	donor_gain	1.0000
8:22581531:GTAG:G	donor_loss	1.0000
8:22581532:T:C	donor_loss	1.0000
8:22584816:CTCA:C	acceptor_loss	1.0000
8:22584819:A:AG	acceptor_gain	1.0000
8:22584819:AG:A	acceptor_gain	1.0000
8:22584820:G:GT	acceptor_gain	1.0000
8:22584820:GG:G	acceptor_gain	1.0000
8:22584820:GGT:G	acceptor_gain	1.0000
8:22584820:GGTC:G	acceptor_gain	1.0000
8:22584820:GGTCT:G	acceptor_gain	1.0000
8:22584890:GGTA:G	donor_loss	1.0000
8:22584891:G:GG	donor_gain	1.0000

AlphaMissense

2256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22580648:T:C	F15S	0.999
8:22581431:T:A	I49N	0.998
8:22581491:T:C	I69T	0.998
8:22593788:T:C	C313R	0.998
8:22593851:T:C	C334R	0.998
8:22580647:T:C	F15L	0.997
8:22580649:C:A	F15L	0.997
8:22580649:C:G	F15L	0.997
8:22580660:G:A	G19E	0.997
8:22593790:T:G	C313W	0.997
8:22593827:T:C	F326L	0.997
8:22593829:C:A	F326L	0.997
8:22593829:C:G	F326L	0.997
8:22593851:T:A	C334S	0.997
8:22593852:G:A	C334Y	0.997
8:22593852:G:C	C334S	0.997
8:22580654:T:C	I17T	0.996
8:22581431:T:G	I49S	0.996
8:22581440:T:A	I52N	0.996
8:22591643:T:C	C286R	0.996
8:22593789:G:A	C313Y	0.996
8:22593810:T:C	L320P	0.996
8:22593852:G:T	C334F	0.996
8:22593853:T:G	C334W	0.996
8:22580641:T:A	W13R	0.995
8:22580641:T:C	W13R	0.995
8:22580648:T:G	F15C	0.995
8:22581440:T:C	I52T	0.995
8:22581479:C:A	A65D	0.995
8:22589702:T:C	F242L	0.995

dbSNP variants (sampled 300 via entrez): RS1000049085 (8:22586688 C>T), RS1000238811 (8:22594771 T>C), RS1000292520 (8:22591196 T>G), RS1000352024 (8:22596576 A>G), RS1000411599 (8:22589448 C>G,T), RS1000555990 (8:22581895 C>T), RS1000558866 (8:22578294 A>G), RS1000567184 (8:22588476 T>G), RS1000572976 (8:22596149 G>A), RS1000740890 (8:22590773 T>C), RS1000899514 (8:22592615 G>A), RS1000910313 (8:22587569 G>T), RS1000940134 (8:22583417 C>T), RS1001137466 (8:22587213 C>G,T), RS1001414485 (8:22595103 GCT>G)

Disease associations

OMIM: gene MIM:609722 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004902_25	Parkinson’s disease	3.000000e-08
GCST005901_1	Survival in breast cancer (estrogen-receptor positive)	2.000000e-08
GCST005901_2	Survival in breast cancer (estrogen-receptor positive)	2.000000e-07
GCST010002_271	Refractive error	2.000000e-17
GCST90002400_64	Plateletcrit	1.000000e-20
GCST90002402_43	Platelet count	2.000000e-21

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0000482	event free survival time
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
(+)-JQ1 compound	decreases expression	2
Air Pollutants	affects cotreatment, affects expression, increases abundance	2
Ozone	affects cotreatment, affects expression, increases abundance	2
Testosterone	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
2,4,6-tribromophenol	increases expression	1
daidzein	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects expression, increases abundance, affects cotreatment	1
lead acetate	decreases expression	1
kojic acid	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, affects expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
octa-2,4,6-trienoic acid	decreases expression	1
Am 580	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
glycitein	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1

Clinical trials (associated diseases)

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