PLEKHA7

Summary

PLEKHA7 (pleckstrin homology domain containing A7, HGNC:27049) is a protein-coding gene on chromosome 11p15, encoding Pleckstrin homology domain-containing family A member 7 (Q6IQ23). Required for zonula adherens biogenesis and maintenance.

Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex.

Source: NCBI Gene 144100 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cleft lip/palate (Moderate, GenCC)
• GWAS associations: 35
• Clinical variants (ClinVar): 277 total — 4 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001329630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27049
Approved symbol	PLEKHA7
Name	pleckstrin homology domain containing A7
Location	11p15
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686M22243
Ensembl gene	ENSG00000166689
Ensembl biotype	protein_coding
OMIM	612686
Entrez	144100

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 12 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000332954, ENST00000355661, ENST00000525049, ENST00000525177, ENST00000525581, ENST00000525781, ENST00000528376, ENST00000528637, ENST00000529213, ENST00000530489, ENST00000531066, ENST00000531079, ENST00000531776, ENST00000532079, ENST00000533251, ENST00000533901, ENST00000636090, ENST00000636113, ENST00000637162, ENST00000696749, ENST00000698836, ENST00000917925

RefSeq mRNA: 4 — MANE Select: NM_001329630 NM_001329630, NM_001329631, NM_001410960, NM_175058

CCDS: CCDS31434, CCDS86182, CCDS91448

Canonical transcript exons

ENST00000531066 — 27 exons

Exon	Start	End
ENSE00001311152	16816800	16817322
ENSE00001412274	16851191	16851291
ENSE00001422757	16841547	16841722
ENSE00001422842	16791011	16791199
ENSE00001424127	16852283	16852355
ENSE00001426741	17013989	17014046
ENSE00001432515	17014125	17014201
ENSE00001432543	16826120	16826590
ENSE00002147453	16777297	16779020
ENSE00002176144	17014316	17014414
ENSE00002186769	16786229	16786387
ENSE00003481261	16802972	16803052
ENSE00003497703	16790798	16790915
ENSE00003544060	16854889	16854993
ENSE00003571290	16871099	16871182
ENSE00003575821	16816178	16816264
ENSE00003585318	16794910	16795018
ENSE00003601414	16782754	16782896
ENSE00003605105	16789096	16789296
ENSE00003611581	16801668	16801817
ENSE00003635369	16783700	16783833
ENSE00003643499	16789775	16789878
ENSE00003645497	16855803	16855914
ENSE00003672114	16794488	16794714
ENSE00003693487	16813113	16813166
ENSE00003694431	16800974	16801075
ENSE00003755260	16803227	16803295

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 98.17.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2636 / max 123.1802, expressed in 840 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118841	4.1400	805
118823	0.0901	35
118838	0.0336	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.17	gold quality
pancreatic ductal cell	CL:0002079	96.01	gold quality
lower esophagus mucosa	UBERON:0035834	96.01	gold quality
ventricular zone	UBERON:0003053	95.43	gold quality
kidney epithelium	UBERON:0004819	94.71	silver quality
apex of heart	UBERON:0002098	94.63	gold quality
esophagus mucosa	UBERON:0002469	94.63	gold quality
tibial nerve	UBERON:0001323	94.14	gold quality
metanephros cortex	UBERON:0010533	93.37	gold quality
left ventricle myocardium	UBERON:0006566	92.42	gold quality
right atrium auricular region	UBERON:0006631	92.37	gold quality
ileal mucosa	UBERON:0000331	92.17	gold quality
minor salivary gland	UBERON:0001830	91.92	gold quality
cardiac atrium	UBERON:0002081	91.67	gold quality
heart left ventricle	UBERON:0002084	90.45	gold quality
mucosa of transverse colon	UBERON:0004991	90.08	gold quality
right uterine tube	UBERON:0001302	89.92	gold quality
cardiac ventricle	UBERON:0002082	89.81	gold quality
rectum	UBERON:0001052	89.73	gold quality
adrenal tissue	UBERON:0018303	89.68	gold quality
epithelial cell of pancreas	CL:0000083	89.67	silver quality
mouth mucosa	UBERON:0003729	89.53	gold quality
vagina	UBERON:0000996	89.09	gold quality
saliva-secreting gland	UBERON:0001044	89.09	gold quality
body of stomach	UBERON:0001161	89.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.06	gold quality
heart	UBERON:0000948	88.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.75	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	88.72	gold quality
metanephros	UBERON:0000081	88.56	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	7.98
E-ANND-3	yes	7.19
E-MTAB-7381	no	284.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting PLEKHA7, 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-4692	100.00	67.32	2066
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4318	99.38	66.94	1505

Literature-anchored findings (GeneRIF, showing 25)

• PLEKHA7 binds with p120catenin and non-centrosomal minus end protein Nezha and plays a linker role between adherens junction and non-centrosomal microtubules. (PMID:19041755)
• PLEKHA7 is a cytoplasmic component of the epithelial adherens junction belt, distinct from ZO-1 and E-cadherin (PMID:20808826)
• ZO-1 and PLEKHA7 are paracingulin-interacting proteins that are involved in its recruitment to epithelial tight and adherens junctions, respectively (PMID:21454477)
• Genetic variations in CYP17A1, CACNB2 and PLEKHA7 were related to blood pressure traits and/or hypertension in Chinese She population. (PMID:21963141)
• Overexpression of PLEKHA7 is common in in-vasive lobular carcinomas and could be a molecular marker to differentiate them from invasive ductal carcinomas. (PMID:22542108)
• Axial length, anterior chamber depth and keratometry were not associated with rs3753841 or rs11024102 genotypes including after adjusting for age and sex. (PMID:23505305)
• The three genetic susceptibility loci for primary angle-closure glaucoma did not underlie any major phenotypic diversity in terms of disease severity or progression. (PMID:24474268)
• Specific localization of PLEKHA7 was found within PACG-related structures (iris, ciliary body, and choroid) and blood-aqueous barrier (BAB) structures (posterior iris epithelium, nonpigmented ciliary epithelium, iris and ciliary body microvasculature). (PMID:24801512)
• Our study suggests that rs1676486 and rs12138977 in COL11A1 as well as rs216489 and rs11024102 in PLEKHA7 are associated with an increased risk of PAC/PACG in the Han Chinese population (PMID:24854855)
• This meta-analysis suggests that PLEKHA7 rs11024102 is associated with PACG (primary angle closure glaucoma) in Asian population and COL11A1 rs3753841 has a genetic association with the development of PACG both in Caucasian and Asian populations. (PMID:25732101)
• PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas (PMID:26270346)
• PLEKHA7 localization to adherens junctions is E-cadherin and p120 dependent. (PMID:26302406)
• PLEKHA7 recruits the microprocessor complex and its core components DROSHA and DGCR8 to the zonula adherens, to suppress growth-related signaling via miRNAs (PMID:26302406)
• Familial linkage studies for primary angle-closure glaucoma have been performed and identified PLEKHA7 causative primary glaucoma disease (PMID:26497787)
• our findings support a multi-layered role of PLEKHA7 in converging cytoskeletal dynamics and miRNA-mediated growth regulation at the ZA, with potentially critical implications in cancer that warrant further investigation. (PMID:26822694)
• These results show that the PLEKHA7-PDZD11 complex stabilizes nectins to promote efficient early junction assembly and uncover a new molecular mechanism through which PLEKHA7 recruits PDZ-binding membrane proteins to epithelial adherens junctions. (PMID:27044745)
• No significant association of PLEKHA7 rs11024102, COL11A1 rs3753841 and PCMTD1-ST18 rs1015213 with primary angle closure glaucoma was found among ethnic Han Chinese from Sichuan (PMID:27455018)
• Downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology. (PMID:29016860)
• Cooperative binding of the tandem WW domains of PLEKHA7 to PDZD11 promotes conformation-dependent interaction with tetraspanin 33. (PMID:32371390)
• PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression. (PMID:33525380)
• Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids. (PMID:33878292)
• PLEKHA5, PLEKHA6, and PLEKHA7 bind to PDZD11 to target the Menkes ATPase ATP7A to the cell periphery and regulate copper homeostasis. (PMID:34613798)
• PLEKHA7 signaling is necessary for the growth of mutant KRAS driven colorectal cancer. (PMID:34800542)
• The PLEKHA7-PDZD11 complex regulates the localization of the calcium pump PMCA and calcium handling in cultured cells. (PMID:35714771)
• The hTERT-p50 homodimer inhibits PLEKHA7 expression to promote gastric cancer invasion and metastasis. (PMID:36823376)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekha7b	ENSDARG00000062220
mus_musculus	Plekha7	ENSMUSG00000045659
rattus_norvegicus	Plekha7	ENSRNOG00000024602

Paralogs (3): PLEKHA5 (ENSG00000052126), PLEKHA4 (ENSG00000105559), PLEKHA6 (ENSG00000143850)

Protein

Protein identifiers

Pleckstrin homology domain-containing family A member 7 — Q6IQ23 (reviewed: Q6IQ23)

All UniProt accessions (11): A0A1B0GTN9, A0A1B0GUM1, A0A1B0GUN0, A0A8Q3WLI9, A0A8V8TMS3, E9PIK1, E9PKC0, E9PL74, E9PN45, Q6IQ23, H0YDE2

UniProt curated annotations — full annotation on UniProt →

Function. Required for zonula adherens biogenesis and maintenance. Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site. Mediates docking of ADAM10 to zonula adherens through a PDZD11-dependent interaction with the ADAM10-binding protein TSPAN33.

Subunit / interactions. Interacts with CAMSAP3 and CTNND1. Interacts (via WW domains) with TSPAN33 (via cytoplasmic domain) and with PDZD11; the interaction with TSPAN33 is dependent on PDZD11 being bound to PLEKHA7 and facilitates the docking of ADAM10 to zonula adherens through interaction of TSPAN33 with ADAM10.

Subcellular location. Cell junction. Adherens junction. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6IQ23-1	1	yes
Q6IQ23-2	2
Q6IQ23-3	3

RefSeq proteins (4): NP_001316559, NP_001316560, NP_001397889, NP_778228 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR040392	PKHA4-7_PH	Domain
IPR057971	PKHA4-7_TBCA	Domain

Pfam: PF00169, PF25541

UniProt features (58 total): modified residue 14, compositionally biased region 11, region of interest 8, strand 8, sequence variant 5, domain 3, coiled-coil region 2, splice variant 2, sequence conflict 2, helix 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7KJO	X-RAY DIFFRACTION	1.45
7KJZ	X-RAY DIFFRACTION	2.43
7KK7	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IQ23-F1	57.68	0.21

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 (14): 536, 545, 569, 604, 608, 612, 858, 860, 867, 870, 871, 903, 907, 986

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (6): cell-cell adhesion mediated by cadherin (GO:0044331), zonula adherens maintenance (GO:0045218), pore complex assembly (GO:0046931), epithelial cell-cell adhesion (GO:0090136), vasodilation (GO:0042311), cell-cell adhesion (GO:0098609)

GO Molecular Function (2): delta-catenin binding (GO:0070097), protein binding (GO:0005515)

GO Cellular Component (13): nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), zonula adherens (GO:0005915), cell junction (GO:0030054), pore complex (GO:0046930), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell-cell junction (GO:0005911), adherens junction (GO:0005912), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell-cell adhesion	2
adherens junction maintenance	1
protein-containing complex assembly	1
blood vessel diameter maintenance	1
cell adhesion	1
protein binding	1
binding	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
adherens junction	1
apical junction complex	1
membrane protein complex	1
extracellular vesicle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
anchoring junction	1
cell-cell junction	1
cell junction	1

Protein interactions and networks

STRING

2006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHA7	CAMSAP3	Q9P1Y5	991
PLEKHA7	KIFC3	Q9BVG8	955
PLEKHA7	CTNND1	O60716	946
PLEKHA7	CGNL1	Q0VF96	826
PLEKHA7	CGN	Q9P2M7	783
PLEKHA7	PDZD11	Q5EBL8	767
PLEKHA7	TJP1	Q07157	728
PLEKHA7	PCMTD1	Q96MG8	728
PLEKHA7	KIF3C	O14782	703
PLEKHA7	AFDN	P55196	651
PLEKHA7	CDH17	Q12864	618
PLEKHA7	COL11A1	P12107	583
PLEKHA7	EEIG1	Q5T9C2	580
PLEKHA7	CTNNA1	P35221	577
PLEKHA7	CDH1	P12830	567

IntAct

136 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CDH1	CTNND1	psi-mi:“MI:0914”(association)	0.730
PLEKHA7	YWHAE	psi-mi:“MI:0915”(physical association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CDH1	PLEKHA7	psi-mi:“MI:0403”(colocalization)	0.700
PLEKHA7	CDH1	psi-mi:“MI:0403”(colocalization)	0.700
PLEKHA7	CTNND1	psi-mi:“MI:0914”(association)	0.640
CTNND1	PLEKHA7	psi-mi:“MI:2364”(proximity)	0.640
PLEKHA7	CTNND1	psi-mi:“MI:0915”(physical association)	0.640
PLEKHA7	CTNND1	psi-mi:“MI:0403”(colocalization)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
AGO2	PLEKHA7	psi-mi:“MI:0403”(colocalization)	0.570
PLEKHA7	AGO2	psi-mi:“MI:0914”(association)	0.570
AGO2	PLEKHA7	psi-mi:“MI:2364”(proximity)	0.570
AGO2	PLEKHA7	psi-mi:“MI:0915”(physical association)	0.570
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (158): PLEKHA7 (Affinity Capture-MS), PLEKHA7 (Affinity Capture-MS), PLEKHA7 (Proximity Label-MS), PLEKHA7 (Proximity Label-MS), PLEKHA7 (Affinity Capture-MS), PLEKHA7 (Proximity Label-MS), PLEKHA7 (Affinity Capture-MS), PLEKHA7 (Affinity Capture-MS), PLEKHA7 (Affinity Capture-MS), KIF13B (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), PLEKHA7 (Affinity Capture-MS), GIGYF1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), PLEKHA7 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3PDQ1, A0M8S4, A0M8T5, A5GFW5, B6RSP1, B9EJA2, D4A039, E9Q0S6, O00750, O35177, Q00PJ1, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07E15, Q07E28, Q07E41, Q08EC4, Q09YG9, Q09YI1, Q09YK4, Q09YM8, Q108T9, Q14511, Q155Q3, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2QL82, Q2QLA2, Q2QLB3, Q2QLF8, Q2QLG9, Q2VUH7, Q3UIL6, Q5JV73, Q61140

Diamond homologs: B6RSP1, D3ZL52, G9CGD6, O08967, O43739, P54644, P60669, P97434, P97696, Q3UIL6, Q5DU31, Q6IQ23, Q6WCQ1, Q6ZNL6, Q7TQG1, Q80UZ0, Q80VL0, Q80YA9, Q86IV4, Q8BH49, Q8C4V1, Q8N264, Q8N4B1, Q8VC98, Q8WWN9, Q8WXI2, Q99KW3, Q9ERE6, Q9ERS5, Q9H4M7, Q9HAU0, Q9HB19, Q9Y2H5, Q9Z1T4, A2A5R2, D4A631, F4IXW2, F4JN05, F4JSZ5, F4K2K3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PLEKHA7	“up-regulates activity”	TSPAN33	binding
PLEKHA7	“up-regulates activity”	PDZD11	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	77.9×	1e-11
Activation of BAD and translocation to mitochondria	7	77.2×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	68.2×	4e-10
Activation of BH3-only proteins	7	50.4×	3e-09
RHO GTPases activate PKNs	8	36.8×	2e-09
Intrinsic Pathway for Apoptosis	7	29.7×	9e-08
FOXO-mediated transcription	6	29.2×	1e-06
Apoptosis	9	21.9×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	23.4×	2e-04
positive regulation of autophagy	5	11.1×	6e-03
regulation of small GTPase mediated signal transduction	6	9.2×	5e-03
intracellular protein localization	8	8.9×	1e-03
protein phosphorylation	9	6.5×	3e-03
cilium assembly	8	6.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	4
Uncertain significance	201
Likely benign	37
Benign	11

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2635559	NM_001329630.2(PLEKHA7):c.3357+2T>G	Likely pathogenic
834022	NM_001329630.2(PLEKHA7):c.1631G>A (p.Gly544Asp)	Likely pathogenic
834023	NM_001329630.2(PLEKHA7):c.1537C>T (p.Arg513Trp)	Likely pathogenic
834024	NM_001329630.2(PLEKHA7):c.1985A>G (p.Asp662Gly)	Likely pathogenic

SpliceAI

5621 predictions. Top by Δscore:

Variant	Effect	Δscore
11:16789292:GGTCT:G	acceptor_gain	1.0000
11:16789293:GTCT:G	acceptor_gain	1.0000
11:16789295:CT:C	acceptor_gain	1.0000
11:16789297:C:CC	acceptor_gain	1.0000
11:16789297:CT:C	acceptor_loss	1.0000
11:16789298:T:A	acceptor_loss	1.0000
11:16789312:C:CT	acceptor_gain	1.0000
11:16789313:A:T	acceptor_gain	1.0000
11:16789773:A:AC	donor_gain	1.0000
11:16789774:C:CC	donor_gain	1.0000
11:16789877:CC:C	acceptor_gain	1.0000
11:16789877:CCCT:C	acceptor_gain	1.0000
11:16789878:CCT:C	acceptor_gain	1.0000
11:16789879:C:CC	acceptor_gain	1.0000
11:16789879:C:T	acceptor_gain	1.0000
11:16789880:T:C	acceptor_gain	1.0000
11:16789880:T:TC	acceptor_gain	1.0000
11:16789883:G:GC	acceptor_gain	1.0000
11:16790913:CACCT:C	acceptor_loss	1.0000
11:16790915:CCTGT:C	acceptor_loss	1.0000
11:16790916:C:CA	acceptor_loss	1.0000
11:16790917:T:A	acceptor_loss	1.0000
11:16791009:AC:A	donor_gain	1.0000
11:16791010:CC:C	donor_gain	1.0000
11:16791031:A:AC	donor_gain	1.0000
11:16791032:C:CC	donor_gain	1.0000
11:16791043:C:CA	donor_gain	1.0000
11:16791055:T:TA	donor_gain	1.0000
11:16791056:C:A	donor_gain	1.0000
11:16791198:TCCTG:T	acceptor_gain	1.0000

AlphaMissense

8288 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:16854892:C:A	K173N	1.000
11:16854892:C:G	K173N	1.000
11:16817088:C:A	W526C	0.999
11:16817088:C:G	W526C	0.999
11:16817090:A:G	W526R	0.999
11:16817090:A:T	W526R	0.999
11:16841602:A:G	W273R	0.999
11:16841602:A:T	W273R	0.999
11:16841634:A:G	F262S	0.999
11:16851195:A:G	F231S	0.999
11:16851263:G:C	S208R	0.999
11:16851263:G:T	S208R	0.999
11:16851265:T:G	S208R	0.999
11:16852317:A:C	F187L	0.999
11:16852317:A:T	F187L	0.999
11:16852318:A:G	F187S	0.999
11:16852319:A:G	F187L	0.999
11:16852322:A:G	W186R	0.999
11:16852322:A:T	W186R	0.999
11:16852334:A:G	W182R	0.999
11:16852334:A:T	W182R	0.999
11:16854894:T:C	K173E	0.999
11:16854899:A:G	L171P	0.999
11:16789217:C:G	R1079P	0.998
11:16791074:C:A	K957N	0.998
11:16791074:C:G	K957N	0.998
11:16801705:A:G	L757P	0.998
11:16803015:A:G	L705P	0.998
11:16851255:A:G	L211S	0.998
11:16852312:A:G	L189P	0.998

dbSNP variants (sampled 300 via entrez): RS1000010992 (11:16825817 T>C), RS1000018439 (11:16946566 G>C), RS1000064402 (11:16951260 A>G,T), RS1000071100 (11:16864892 T>A,C), RS1000076120 (11:16820001 G>A), RS1000076682 (11:16837346 A>G), RS1000084868 (11:16826531 T>C), RS1000097613 (11:16905510 C>G,T), RS1000101164 (11:16969783 G>A), RS1000116316 (11:16974914 A>G), RS1000121730 (11:16865223 C>G,T), RS1000123640 (11:16989566 T>C), RS1000125366 (11:16851233 A>G), RS1000136401 (11:16810479 T>C), RS1000148678 (11:16920762 C>T)

Disease associations

OMIM: gene MIM:612686 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cleft lip/palate	Moderate	Autosomal dominant

Mondo (1): cleft lip/palate (MONDO:0016044)

Orphanet (1): Cleft lip with or without cleft palate (Orphanet:1991)

HPO phenotypes

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

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST000393_4	Systolic blood pressure	2.000000e-09
GCST000396_7	Diastolic blood pressure	1.000000e-06
GCST001235_1	Blood pressure	7.000000e-06
GCST001236_14	Blood pressure	3.000000e-08
GCST001649_3	Glaucoma (primary angle closure)	5.000000e-12
GCST003467_16	Glaucoma (primary angle closure)	2.000000e-18
GCST003467_17	Glaucoma (primary angle closure)	8.000000e-19
GCST003825_10	Systolic blood pressure change trajectory	2.000000e-07
GCST003825_6	Systolic blood pressure change trajectory	8.000000e-06
GCST004776_57	Systolic blood pressure	3.000000e-06
GCST004777_24	Diastolic blood pressure	1.000000e-06
GCST005194_215	Coronary artery disease	1.000000e-06
GCST005196_47	Coronary artery disease	7.000000e-08
GCST005580_251	Intraocular pressure	1.000000e-10
GCST005580_264	Intraocular pressure	3.000000e-10
GCST005951_67	Body mass index	6.000000e-09
GCST005951_68	Body mass index	3.000000e-09
GCST006166_9	Diastolic blood pressure x alcohol consumption interaction (2df test)	6.000000e-10
GCST006167_8	Mean arterial pressure x alcohol consumption interaction (2df test)	2.000000e-10
GCST006231_46	Mean arterial pressure	3.000000e-11
GCST006258_20	Diastolic blood pressure	4.000000e-11
GCST006259_4	Systolic blood pressure	6.000000e-10
GCST006394_87	Intraocular pressure	4.000000e-16
GCST006412_117	Intraocular pressure	7.000000e-21
GCST006434_28	Systolic blood pressure x alcohol consumption interaction (2df test)	6.000000e-16
GCST006434_37	Systolic blood pressure x alcohol consumption interaction (2df test)	5.000000e-13
GCST006585_2449	Blood protein levels	1.000000e-08
GCST006976_32	Macular thickness	7.000000e-19
GCST007094_15	Diastolic blood pressure	3.000000e-06
GCST007099_97	Systolic blood pressure	2.000000e-07

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0006944	systolic blood pressure change measurement
EFO:0004695	intraocular pressure measurement
EFO:0004340	body mass index
EFO:0004329	alcohol drinking

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296241 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
phenethyl isothiocyanate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	affects expression	1
Estradiol	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4420444	Binding	Binding affinity to N-terminal GST-tagged PLEKHA7 PHD (unknown origin) by SPR assay	Compounds, compositions and methods for inhibiting cnksr1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04234971	PHASE4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	PHASE4	RECRUITING	Ketorolac in Palatoplasty
NCT03766217	PHASE3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	PHASE3	RECRUITING	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT00930124	PHASE2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT06408337	PHASE1/PHASE2	RECRUITING	Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00156442	Not specified	COMPLETED	A Study to Examine the Relationship Between Sleep Apnea and Cleft Lip/Palate
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01871623	Not specified	UNKNOWN	One-Piece Le Fort I Osteotomy Versus Segmental Le Fort I Osteotomy
NCT01932164	Not specified	COMPLETED	Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02789787	Not specified	COMPLETED	Clinical Effectiveness of Late Maxillary Protraction for Cleft Lip and Palate
NCT02845193	Not specified	COMPLETED	Effect of Novel Nasoalveolar Molding Techniques on Parents’ Satisfaction and Short Term Treatment Outcomes in Unilateral Cleft Lip and Palate Infants: A Randomized Controlled Trial
NCT02881606	Not specified	COMPLETED	Evaluation of the Clinical Effectiveness of Naso-alveolar Molding (NAM) Versus Computer Aided Design NAM (CAD/NAM) in Infants With Bilateral Cleft Lip and Palate: A Randomized Clinical Trial
NCT03011489	Not specified	UNKNOWN	Parent’s Satisfaction and Evaluation of Postsurgical Outcomes in Unilateral Cleft Lip / Palate Newly Born Infants With / Without Vacuum Formed Nasoalveolar Molding Aligners : A Controlled Clinical Trial
NCT03065686	Not specified	RECRUITING	Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing
NCT03165331	Not specified	UNKNOWN	Online Psychosocial Support for Young People With a Visible Difference: A Randomised Control Study
NCT03217890	Not specified	UNKNOWN	the Relationship Between Cleft Lip and / or Palate (Different Types) and ABO Blood Groups.
NCT03308266	Not specified	COMPLETED	Electromyographic Analysis of the Masticatory Muscles in Cleft Lip and Palate Children With Temporomandibular Disorders
NCT03395015	Not specified	COMPLETED	Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations
NCT03514563	Not specified	TERMINATED	Three Dimensional Facial Growth Analysis
NCT03563495	Not specified	COMPLETED	Tissue Engineered Constructs for Alveolar Cleft Repair
NCT03582111	Not specified	COMPLETED	Ultrasound Diagnosis of Cleft Lip and Palate
NCT03686761	Not specified	COMPLETED	Periodontal Changes Following Mid Maxillary Distraction
NCT03708406	Not specified	COMPLETED	Otologic and Rhinologic Outcomes in Children With Clef Palate
NCT03740841	Not specified	TERMINATED	Evaluation of the Effects of LUNII on Pre-operative Anxiety and on the Post-operative Period in Children With Cleft Lip and Palate Admitted for Alveolar Bone Graft: Pilot Study
NCT03750708	Not specified	WITHDRAWN	Oral Hygiene and Connected Toothbrush Before Alveolar Bone Graft for Cleft Lip and Palate
NCT03839290	Not specified	UNKNOWN	Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty
NCT03877666	Not specified	COMPLETED	Assessment of the Influence of Cleft Repair on Microcirculation of the Palate
NCT03976609	Not specified	COMPLETED	Three Dimensional Changes on Nasal Septum and Alveolar Cleft After Maxillary Expansion
NCT04108416	Not specified	COMPLETED	Unilateral Cleft Repair in One Surgery With Pure Primary Healing
NCT04236466	Not specified	UNKNOWN	Transverse Dento-skeletal Effects of Two Rapid Palatal Expansion Appliances in Cleft Lip and Palate Patients
NCT04331379	Not specified	COMPLETED	Effectiveness of Nasal-alar Elevator Combined With Taping Vs. Taping Alone on Improving the Nose Esthetics and Maxillary Arch Dimensions in Infants With Unilateral Complete Cleft Lip and Palate
NCT04331977	Not specified	COMPLETED	Effectiveness of Two Maxillary Expanders in Improving the Transverse Skeletal and Dental Dimensions in Patients With Cleft Lip and Palate
NCT04354116	Not specified	UNKNOWN	MARPE in Patients With Cleft Lip and Palate
NCT04369638	Not specified	TERMINATED	Fabrication of Naso-alveolar Molding (NAM) Appliance in Cleft Lip and Palate (CLP) From Digital Magnetic Resonance Imaging (MRI) Face Scan
NCT04381078	Not specified	UNKNOWN	Methods of Providing Information Prior to an Alveolar Bone Graft
NCT04384276	Not specified	COMPLETED	Weigh Easy: Simplifying Home Weight Monitoring for Infants
NCT04422847	Not specified	RECRUITING	Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect