PLEKHA1

Summary

PLEKHA1 (pleckstrin homology domain containing A1, HGNC:14335) is a protein-coding gene on chromosome 10q26.13, encoding Pleckstrin homology domain-containing family A member 1 (Q9HB21). Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides.

This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.

Source: NCBI Gene 59338 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 78 total
• Druggable target: yes
• MANE Select transcript: NM_001001974

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14335
Approved symbol	PLEKHA1
Name	pleckstrin homology domain containing A1
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	TAPP1
Ensembl gene	ENSG00000107679
Ensembl biotype	protein_coding
OMIM	607772
Entrez	59338

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 33 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000368988, ENST00000368989, ENST00000368990, ENST00000392799, ENST00000433307, ENST00000463663, ENST00000481451, ENST00000494222, ENST00000878213, ENST00000878214, ENST00000878215, ENST00000878216, ENST00000878217, ENST00000878218, ENST00000878219, ENST00000878220, ENST00000878221, ENST00000878222, ENST00000878223, ENST00000878224, ENST00000878225, ENST00000878226, ENST00000878227, ENST00000878228, ENST00000878229, ENST00000878230, ENST00000878231, ENST00000919448, ENST00000919449, ENST00000919450, ENST00000949908, ENST00000949909, ENST00000949910, ENST00000949911, ENST00000949912

RefSeq mRNA: 30 — MANE Select: NM_001001974 NM_001001974, NM_001195608, NM_001330178, NM_001377230, NM_001377231, NM_001377232, NM_001377234, NM_001377235, NM_001377237, NM_001377238, NM_001377240, NM_001377241, NM_001377242, NM_001377243, NM_001377244, NM_001377245, NM_001377246, NM_001377247, NM_001377248, NM_001377249, NM_001377250, NM_001377251, NM_001377252, NM_001377253, NM_001377254, NM_001377255, NM_001377256, NM_001377257, NM_001377258, NM_021622

CCDS: CCDS55730, CCDS7629, CCDS81517

Canonical transcript exons

ENST00000368990 — 12 exons

Exon	Start	End
ENSE00003244091	122400343	122400388
ENSE00003244326	122429624	122432345
ENSE00003287400	122406576	122406673
ENSE00003327871	122417900	122417968
ENSE00003342675	122426942	122427031
ENSE00003397141	122424896	122424959
ENSE00003454592	122424199	122424263
ENSE00003546286	122393181	122393341
ENSE00003585558	122415859	122416002
ENSE00003601594	122397918	122397974
ENSE00003686604	122412920	122413045
ENSE00003927861	122374708	122374806

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8654 / max 159.4089, expressed in 1720 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107443	14.8855	1701
107442	2.2012	1005
107441	0.7949	471
107444	0.6673	365
206018	0.3166	151

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	98.01	gold quality
sperm	CL:0000019	97.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.49	gold quality
skin of hip	UBERON:0001554	97.27	gold quality
middle temporal gyrus	UBERON:0002771	97.00	gold quality
postcentral gyrus	UBERON:0002581	96.89	gold quality
gingival epithelium	UBERON:0001949	96.81	gold quality
gingiva	UBERON:0001828	96.58	gold quality
parietal lobe	UBERON:0001872	96.46	gold quality
synovial joint	UBERON:0002217	96.34	gold quality
endothelial cell	CL:0000115	95.92	gold quality
male germ cell	CL:0000015	95.72	gold quality
primary visual cortex	UBERON:0002436	95.71	gold quality
superior frontal gyrus	UBERON:0002661	95.64	gold quality
mammalian vulva	UBERON:0000997	95.49	gold quality
entorhinal cortex	UBERON:0002728	95.15	gold quality
penis	UBERON:0000989	95.08	gold quality
occipital lobe	UBERON:0002021	94.97	gold quality
heart right ventricle	UBERON:0002080	94.91	gold quality
islet of Langerhans	UBERON:0000006	94.86	gold quality
secondary oocyte	CL:0000655	94.82	gold quality
germinal epithelium of ovary	UBERON:0001304	94.74	gold quality
nipple	UBERON:0002030	94.55	gold quality
jejunal mucosa	UBERON:0000399	94.42	gold quality
tibia	UBERON:0000979	94.36	gold quality
endometrium	UBERON:0001295	94.36	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.68	gold quality
corpus callosum	UBERON:0002336	93.66	gold quality
zone of skin	UBERON:0000014	93.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1001.47
E-CURD-114	yes	61.26
E-HCAD-10	yes	26.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

167 targeting PLEKHA1, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Literature-anchored findings (GeneRIF, showing 9)

• TAPP1 binds to protein tyrosine phosphatase PTPL1. (PMID:14516276)
• syntrophins regulate the localization of TAPP1, which may be important for remodeling the actin cytoskeleton in response to growth factor stimulation (PMID:15485858)
• PLEKHA1 is strongly implicated as primarily responsible for the evidence of linkage of age-related maculopathy (ARM) to the 10q26 locus and as a major contributor to ARM.susceptibility. (PMID:16080115)
• Although a role for PLEKHA1 could not be totally excluded, there was a four times higher age-related macular degeneration risk was associated with haplotype “A-T-A” involving “PLEKHA1-LOC387715-HTRA1” risk alleles. (PMID:18079691)
• Independent of CFH genotype or smoking history, an individual’s risk of AMD (age-related macular degeneration) could be increased or decreased, depending on their genotype or haplotype in the 10q26 region. (PMID:18164066)
• This study provides evidence of the joint contribution of genetic variants in PLEKHA1/ARMS2/HTRA1 to age-related macular degeneration risk. (PMID:24013816)
• CX3CR1 (T280M and V249I) and PLEKHA1 (A320T) polymorphisms were not found to be associated with age-related macular degeneration in an Indian population. (PMID:25050486)
• Studies indicate that the high-risk allele of the 10q26 locus encompasses three genes, PLEKHA1, ARMS2, and HTRA1 with high linkage disequilibrium. (PMID:26427389)
• investigated the association of PLEKHA1 958A/G, polymorphisms with Age-Related Macular Degeneration (AMD) risk. PLEKHA1 958A/G polymorphism was associated with a decreased AMD risk (additive model: aOR=0.722, 95% CI=0.450-0.979, P=0.019; allele model: aOR=0.883, 95% CI=0.736-0.992, P=0.014) (PMID:29565837)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekha1a	ENSDARG00000030064
danio_rerio	plekha1b	ENSDARG00000094504
mus_musculus	Plekha1	ENSMUSG00000040268
rattus_norvegicus	Plekha1	ENSRNOG00000020497

Paralogs (1): PLEKHA2 (ENSG00000169499)

Protein

Protein identifiers

Pleckstrin homology domain-containing family A member 1 — Q9HB21 (reviewed: Q9HB21)

Alternative names: Tandem PH domain-containing protein 1

All UniProt accessions (3): Q9HB21, Q5RGS4, R4GMZ9

UniProt curated annotations — full annotation on UniProt →

Function. Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane.

Subunit / interactions. Interacts with MPDZ and PTPN13.

Subcellular location. Cytoplasm. Cell membrane. Nucleus.

Tissue specificity. Highly expressed in skeletal muscle, thymus, pancreas, placenta and lung. Detected at low levels in brain, heart, peripheral blood leukocytes, testis, ovary, spinal cord, thyroid, kidney, liver, small intestine and colon.

Domain organisation. Binds to membranes enriched in PtdIns3,4P2 via the C-terminal PH domain.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HB21-1	1	yes
Q9HB21-2	2

RefSeq proteins (30): NP_001001974, NP_001182537, NP_001317107, NP_001364159, NP_001364160, NP_001364161, NP_001364163, NP_001364164, NP_001364166, NP_001364167, NP_001364169, NP_001364170, NP_001364171, NP_001364172, NP_001364173, NP_001364174, NP_001364175, NP_001364176, NP_001364177, NP_001364178, NP_001364179, NP_001364180, NP_001364181, NP_001364182, NP_001364183, NP_001364184, NP_001364185, NP_001364186, NP_001364187, NP_067635 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR051707	PI-Interact_SigTrans_Reg	Family

Pfam: PF00169

UniProt features (30 total): mutagenesis site 9, strand 7, helix 3, domain 2, region of interest 2, modified residue 2, chain 1, turn 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1EAZ	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HB21-F1	71.25	0.39

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): 332, 362

Mutagenesis-validated functional residues (9):

Position	Phenotype
28	no effect on phosphatidylinositide binding.
203–205	abolishes phosphatidylinositide binding.
203–205	binds both ptdins3,4p2 and ptdins3,4,5p3.
203–204	binds both ptdins3,4p2 and ptdins3,4,5p3.
203	binds both ptdins3,4p2 and ptdins3,4,5p3.
204	no effect.
205	no effect.
207	no effect.
211	abolishes phosphatidylinositide binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane

MSigDB gene sets: 368 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_BODY_MORPHOGENESIS, GCM_PTPRD, PAX4_01, TGCGCANK_UNKNOWN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_RUFFLE, GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MODULE_313

GO Biological Process (18): luteinization (GO:0001553), spermatogenesis (GO:0007283), androgen metabolic process (GO:0008209), estrogen metabolic process (GO:0008210), post-embryonic development (GO:0009791), ruffle organization (GO:0031529), Leydig cell differentiation (GO:0033327), multicellular organism growth (GO:0035264), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), establishment of protein localization (GO:0045184), platelet-derived growth factor receptor signaling pathway (GO:0048008), skeletal system morphogenesis (GO:0048705), B cell receptor signaling pathway (GO:0050853), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), roof of mouth development (GO:0060021), face morphogenesis (GO:0060325), cellular response to hydrogen peroxide (GO:0070301), female gonad development (GO:0008585)

GO Molecular Function (5): phospholipid binding (GO:0005543), PDZ domain binding (GO:0030165), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (8): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), ruffle membrane (GO:0032587), extracellular exosome (GO:0070062), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PI Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
developmental process involved in reproduction	2
steroid metabolic process	2
hormone metabolic process	2
multicellular organismal process	2
binding	2
female gonad development	1
ovulation cycle process	1
male gamete generation	1
multicellular organism development	1
plasma membrane bounded cell projection organization	1
male gonad development	1
cell differentiation	1
developmental growth	1
intracellular signaling cassette	1
establishment of localization	1
cell surface receptor protein tyrosine kinase signaling pathway	1
skeletal system development	1
animal organ morphogenesis	1
antigen receptor-mediated signaling pathway	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
anatomical structure development	1
anatomical structure morphogenesis	1
head morphogenesis	1
face development	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
gonad development	1
development of primary female sexual characteristics	1
lipid binding	1
protein domain specific binding	1
phosphatidylinositol bisphosphate binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
ruffle	1

Protein interactions and networks

STRING

1074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHA1	ARMS2	P0C7Q2	915
PLEKHA1	CFH	P08603	847
PLEKHA1	HTRA1	Q92743	730
PLEKHA1	HMCN1	Q96RW7	666
PLEKHA1	EFEMP1	Q12805	605
PLEKHA1	C2	P06681	587
PLEKHA1	BTBD16	Q32M84	575
PLEKHA1	PLEKHA3	Q9HB20	546
PLEKHA1	PTPN13	Q12923	542
PLEKHA1	PLCD1	P51178	480
PLEKHA1	INPP4A	Q96PE3	399
PLEKHA1	INPPL1	O15357	390
PLEKHA1	SRF	P11831	387
PLEKHA1	CFHR1	Q03591	370
PLEKHA1	CFHR3	Q02985	370

IntAct

188 interactions, top by confidence:

A	B	Type	Score
PLEKHA1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.770
MPDZ	PLEKHA1	psi-mi:“MI:0915”(physical association)	0.770
PLEKHA1	MPDZ	psi-mi:“MI:0915”(physical association)	0.770
PLEKHA1	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.680
PTPN13	PLEKHA1	psi-mi:“MI:0915”(physical association)	0.680
PLEKHA1	PTPN13	psi-mi:“MI:0915”(physical association)	0.680
PTPN13	PLEKHA1	psi-mi:“MI:0403”(colocalization)	0.680
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
PPP1R15A	POP4	psi-mi:“MI:0914”(association)	0.530
PLEKHA1	PBX2	psi-mi:“MI:0914”(association)	0.530
PLEKHA1	SH3BP4	psi-mi:“MI:0915”(physical association)	0.510
CLDN14	PLEKHA1	psi-mi:“MI:0915”(physical association)	0.490
PLEKHA1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
PLEKHA1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
PLEKHA1	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (136): PLEKHA1 (Proximity Label-MS), PLEKHA1 (Proximity Label-MS), PLEKHA1 (Proximity Label-MS), PLEKHA1 (Proximity Label-MS), PLEKHA1 (Affinity Capture-MS), PLEKHA1 (Proximity Label-MS), PLEKHA1 (Affinity Capture-MS), MSL3 (Affinity Capture-MS), WDR45B (Affinity Capture-MS), PBX2 (Affinity Capture-MS), PLEKHA1 (Biochemical Activity), PLEKHA1 (Two-hybrid), PLEKHA1 (Proximity Label-MS), PLEKHA1 (Proximity Label-MS), PLEKHA1 (Proximity Label-MS)

ESM2 similar proteins: A5D7P8, A6QLK2, F1LQ48, O55047, O95628, P25916, P35226, P59326, P97855, Q08CW1, Q0VCY1, Q0VCZ3, Q12906, Q13148, Q13283, Q1ECX4, Q32KX7, Q32LC7, Q3SWT1, Q3ZBD9, Q4R5D9, Q5FVP2, Q5PRC7, Q5R601, Q5R8L2, Q5RB87, Q5SDR3, Q5U2U0, Q5ZLN5, Q64213, Q66K94, Q6DE02, Q6NRF9, Q86UE8, Q8BGW5, Q8BT14, Q8C0V0, Q8R2Y9, Q90ZY6, Q91YT7

Diamond homologs: A6QLU3, Q00IB7, Q13480, Q2WGN9, Q86SQ0, Q8BUL6, Q8K1N2, Q8WWW8, Q99PF6, Q9EQH1, Q9HB21, Q9QYY0, Q9ULM0, Q9UQC2, Q9VZZ9, Q9W5D0, Q9Z1S8, A0JN54, A8JQ65, B3LXF2, B3NYS4, B4I4Y1, B4JHJ7, B4K6T8, B4PRE2, B4R0A5, D3YWQ0, D3YXJ0, D3YZU1, D3ZEY4, E9PUQ8, F1MAB7, F4JKI3, F4JQ95, G9CGD6, O08560, O75912, O88673, P09216, P10830

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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
Activation of BAD and translocation to mitochondria	7	53.3×	2e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	47.0×	5e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	47.0×	5e-09
Activation of BH3-only proteins	7	34.8×	4e-08
Ras activation upon Ca2+ influx through NMDA receptor	5	28.6×	2e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	27.2×	2e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	27.2×	2e-05
Assembly and cell surface presentation of NMDA receptors	10	25.4×	9e-10

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	45.0×	9e-12
protein localization to synapse	6	35.6×	3e-06
receptor clustering	7	33.9×	6e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	23.1×	3e-05
establishment of cell polarity	6	17.8×	9e-05
protein targeting	6	17.0×	1e-04
ephrin receptor signaling pathway	5	13.3×	2e-03
bicellular tight junction assembly	5	12.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2204 predictions. Top by Δscore:

Variant	Effect	Δscore
10:122393176:TACA:T	acceptor_loss	1.0000
10:122393178:CA:C	acceptor_loss	1.0000
10:122393179:A:AG	acceptor_gain	1.0000
10:122393179:AGT:A	acceptor_gain	1.0000
10:122393180:G:GG	acceptor_gain	1.0000
10:122393180:GT:G	acceptor_gain	1.0000
10:122393180:GTG:G	acceptor_gain	1.0000
10:122393180:GTGT:G	acceptor_gain	1.0000
10:122393180:GTGTA:G	acceptor_gain	1.0000
10:122393340:AG:A	donor_loss	1.0000
10:122393341:GG:G	donor_loss	1.0000
10:122393342:G:GC	donor_loss	1.0000
10:122393343:T:A	donor_loss	1.0000
10:122400389:G:GA	donor_loss	1.0000
10:122400389:G:GG	donor_gain	1.0000
10:122400390:TA:T	donor_loss	1.0000
10:122400391:AA:A	donor_loss	1.0000
10:122406574:A:AG	acceptor_gain	1.0000
10:122406575:G:GG	acceptor_gain	1.0000
10:122406669:TTACA:T	donor_gain	1.0000
10:122406674:G:GG	donor_gain	1.0000
10:122412914:TTTCA:T	acceptor_loss	1.0000
10:122412915:TTCA:T	acceptor_loss	1.0000
10:122412917:CAGGT:C	acceptor_loss	1.0000
10:122412918:A:AG	acceptor_gain	1.0000
10:122412918:AGGT:A	acceptor_loss	1.0000
10:122412919:G:GA	acceptor_gain	1.0000
10:122413043:CAGG:C	donor_loss	1.0000
10:122413044:AG:A	donor_loss	1.0000
10:122413045:GG:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000067663 (10:122440585 A>C), RS1000085922 (10:122438682 G>A), RS1000121943 (10:122396113 A>G), RS1000177195 (10:122388606 A>G), RS1000203756 (10:122433525 T>C), RS1000257091 (10:122413560 C>A,G), RS1000286052 (10:122438385 A>G), RS1000381532 (10:122427447 C>A), RS1000387031 (10:122382657 C>T), RS1000471436 (10:122395718 C>T), RS1000480796 (10:122427111 G>A), RS1000540959 (10:122414082 T>C), RS1000543535 (10:122376350 AAG>A), RS1000562592 (10:122438969 G>A), RS1000562872 (10:122427433 C>T)

Disease associations

OMIM: gene MIM:607772 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000611_10	Height	2.000000e-06
GCST001899_2	Age-related macular degeneration	1.000000e-16
GCST001986_3	Age-related macular degeneration	8.000000e-27
GCST001987_1	Age-related macular degeneration (extreme sampling)	3.000000e-29
GCST002352_47	Type 2 diabetes	1.000000e-07
GCST004773_6	Type 2 diabetes	2.000000e-13
GCST004894_1	Type 2 diabetes	2.000000e-08
GCST004894_105	Type 2 diabetes	4.000000e-11
GCST005146_37	Birth weight	6.000000e-09
GCST005795_30	Femoral neck bone mineral density	2.000000e-08
GCST006196_3	Type 1 diabetes in high risk HLA genotype individuals (time to event)	3.000000e-06
GCST006867_95	Type 2 diabetes	1.000000e-10
GCST007847_122	Type 2 diabetes	2.000000e-08
GCST007932_74	Medication use (thyroid preparations)	4.000000e-10
GCST008362_121	Birth weight	3.000000e-14
GCST008362_199	Birth weight	3.000000e-15
GCST008363_118	Offspring birth weight	1.000000e-08
GCST008363_79	Offspring birth weight	4.000000e-08
GCST008839_6	Height	4.000000e-12
GCST009379_366	Type 2 diabetes	1.000000e-13
GCST010002_227	Refractive error	6.000000e-23
GCST010118_119	Type 2 diabetes	1.000000e-10
GCST010571_50	Autoimmune thyroid disease	8.000000e-10
GCST90000025_182	Appendicular lean mass	1.000000e-26
GCST90000654_31	Central corneal thickness	8.000000e-09
GCST90020028_780	Hip circumference adjusted for BMI	3.000000e-12
GCST90020028_781	Hip circumference adjusted for BMI	4.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0007785	femoral neck bone mineral density
EFO:0000409	disease free survival
EFO:0009933	Thyroid preparation use measurement
EFO:0005939	parental genotype effect measurement
EFO:0004980	appendicular lean mass
EFO:0005213	central corneal thickness
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3763005 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.30	IC50	5000	nM	CHEMBL3764684

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation, increases expression	6
bisphenol A	increases expression, affects cotreatment, decreases expression	2
trichostatin A	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects methylation	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases 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
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Hydrogen Peroxide	increases expression, affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Phthalic Acids	affects methylation	1
T-2 Toxin	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Theophylline	affects cotreatment, decreases expression	1
Vitamin E	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	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
CHEMBL3767270	Binding	Antagonist activity at human Tapp1-PH domain (180 to 305 residues) assessed as reduction in PI(3,4)P2/Tapp1-PH interaction after 30 mins by competitive SPR analysis	Inhibition of phosphatidylinositol-3,4,5-trisphosphate binding to the AKT pleckstrin homology domain by 4-amino-1,2,5-oxadiazole derivatives — Medchemcomm

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE52	HAP1 PLEKHA1 (-) 1	Cancer cell line	Male
CVCL_TE53	HAP1 PLEKHA1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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