PPFIA1

Summary

PPFIA1 (PPFI scaffold protein A1, HGNC:9245) is a protein-coding gene on chromosome 11q13.3, encoding Liprin-alpha-1 (Q13136). May regulate the disassembly of focal adhesions.

The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 8500 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 164 total
• MANE Select transcript: NM_003626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9245
Approved symbol	PPFIA1
Name	PPFI scaffold protein A1
Location	11q13.3
Locus type	gene with protein product
Status	Approved
Aliases	LIP.1, LIPRIN
Ensembl gene	ENSG00000131626
Ensembl biotype	protein_coding
OMIM	611054
Entrez	8500

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 18 protein_coding, 8 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay, 4 retained_intron

ENST00000253925, ENST00000389547, ENST00000525530, ENST00000525922, ENST00000526074, ENST00000526262, ENST00000526347, ENST00000526369, ENST00000527612, ENST00000528284, ENST00000528750, ENST00000528853, ENST00000530294, ENST00000530390, ENST00000530548, ENST00000530746, ENST00000530798, ENST00000530932, ENST00000531657, ENST00000532024, ENST00000532443, ENST00000532504, ENST00000532793, ENST00000533894, ENST00000638133, ENST00000644155, ENST00000648755, ENST00000851267, ENST00000851268, ENST00000851269, ENST00000915567, ENST00000915568, ENST00000915569, ENST00000915570, ENST00000966186, ENST00000966187

RefSeq mRNA: 3 — MANE Select: NM_003626 NM_001378006, NM_003626, NM_177423

CCDS: CCDS31627, CCDS31628

Canonical transcript exons

ENST00000253925 — 28 exons

Exon	Start	End
ENSE00002183745	70383003	70384396
ENSE00002188288	70270690	70270914
ENSE00002485330	70325500	70325574
ENSE00002508102	70326597	70326818
ENSE00002530458	70326262	70326363
ENSE00002530514	70324847	70325011
ENSE00002531692	70324402	70324503
ENSE00002711464	70272173	70272436
ENSE00003504686	70339171	70339306
ENSE00003515258	70354301	70354452
ENSE00003548769	70337365	70337427
ENSE00003569321	70372477	70372574
ENSE00003573950	70378030	70378195
ENSE00003575245	70330173	70330319
ENSE00003578668	70333470	70333553
ENSE00003584840	70372215	70372390
ENSE00003586332	70355639	70355811
ENSE00003594557	70338374	70338453
ENSE00003594881	70376532	70376600
ENSE00003606630	70374918	70375093
ENSE00003618141	70382088	70382158
ENSE00003642211	70335563	70335694
ENSE00003647440	70362095	70362176
ENSE00003647551	70343669	70343892
ENSE00003653497	70331960	70332094
ENSE00003661502	70348189	70348420
ENSE00003669202	70356161	70356254
ENSE00003686333	70362288	70362488

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.0249 / max 431.3695, expressed in 1814 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115649	29.3865	1814
115658	0.3092	52
115659	0.1018	36
115656	0.0735	31
115662	0.0577	13
115660	0.0522	21
115657	0.0441	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.61	gold quality
oocyte	CL:0000023	98.60	gold quality
secondary oocyte	CL:0000655	98.23	gold quality
buccal mucosa cell	CL:0002336	97.79	gold quality
sperm	CL:0000019	96.83	gold quality
calcaneal tendon	UBERON:0003701	96.59	gold quality
endothelial cell	CL:0000115	96.57	gold quality
choroid plexus epithelium	UBERON:0003911	96.20	gold quality
tibia	UBERON:0000979	95.88	gold quality
male germ cell	CL:0000015	95.71	gold quality
visceral pleura	UBERON:0002401	95.67	gold quality
parietal pleura	UBERON:0002400	95.63	gold quality
pleura	UBERON:0000977	95.12	gold quality
adenohypophysis	UBERON:0002196	94.98	gold quality
corpus callosum	UBERON:0002336	94.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.76	gold quality
colonic epithelium	UBERON:0000397	94.71	gold quality
germinal epithelium of ovary	UBERON:0001304	94.71	gold quality
hair follicle	UBERON:0002073	94.44	gold quality
pituitary gland	UBERON:0000007	94.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.04	gold quality
left testis	UBERON:0004533	93.86	gold quality
epithelium of nasopharynx	UBERON:0001951	93.82	gold quality
right testis	UBERON:0004534	93.82	gold quality
nasopharynx	UBERON:0001728	93.81	gold quality
testis	UBERON:0000473	93.79	gold quality
palpebral conjunctiva	UBERON:0001812	93.79	gold quality
jejunal mucosa	UBERON:0000399	93.75	gold quality
eye	UBERON:0000970	93.72	gold quality
gastrocnemius	UBERON:0001388	93.69	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.68
E-HCAD-5	no	2.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting PPFIA1, 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-4262	100.00	73.26	3931
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-34C-5P	99.97	70.45	1577

Literature-anchored findings (GeneRIF, showing 24)

• the interaction between ERC2 and liprin-alpha may be involved in the presynaptic localization of liprin-alpha and the molecular organization of presynaptic active zones (PMID:12923177)
• liprin binds to ATP-agarose, challenged by free ATP, not by free GTP. Liprin LH region mutations inhibit liprin phosphorylation stabilized association of liprin with ATP-agarose. Suggests that liprin autophosphorylation regulates its association with LAR. (PMID:16313174)
• regulated degradation of liprinalpha1 is important for proper LAR receptor distribution, and could provide a mechanism for localized control of dendrite and synapse morphogenesis by activity and CaMKII. (PMID:17419996)
• Amplification and overexpression of PPFIA1, a putative 11q13 invasion suppressor gene, is associated with head and neck squamous cell carcinoma (PMID:18196592)
• Liprin is an essential regulator of cell motility that contributes to the effectiveness of cell-edge protrusion. (PMID:19690048)
• Amplification of both PPFIA1 and CCND1 were significantly associated with high-grade breast cancer phenotype but were unrelated to tumor stage or nodal stage (PMID:19787783)
• Data show that increased levels of liprin-alpha1 affected the localization of inactive, low-affinity integrins, while increasing the average size of beta1 integrin-positive focal adhesions. (PMID:20096687)
• These results suggest that an increased expression of Liprin-alpha1 in the brain may be associated with human Intractable epilepsy . (PMID:21157931)
• The results of this study finding suggested that a model by which the self-assembly of SYD-2/Liprin-alpha proteins mediated by the coiled-coil LH1 domain is one of the key steps to the accumulation of presynaptic components at nascent synaptic junctions (PMID:22072677)
• PPFIA1 as a potential functional candidate acute lung injury risk gene (PMID:22295056)
• PPFIA1 was frequently co-amplified with the Cyclin D1 gene in oral carcinomas and could present a biomarker as well as a novel target for specific gene therapy. (PMID:23453270)
• Liprin-alpha1, ERC1a and LL5 also define new highly polarized and dynamic cytoplasmic structures uniquely localized near the protruding cell edge (PMID:24982445)
• results suggested that PPFIA1 functioned with PP2A to promote the dephosphorylation of Kif7, triggering Kif7 localization to the tips of primary cilia and promoting Gli transcriptional activity. (PMID:25492966)
• The human tumor cell line MDA-MB-231 expresses liprin-alpha 1 and is able to promote the formation of metastasis in mice. (PMID:26663347)
• These results indicate that liprin-alpha1 localizes to different adhesion and cytoskeletal structures to regulate vimentin intermediate filament network, thereby altering the invasion and growth properties of the cancer cells. (PMID:27075696)
• This study shows that PPFIA1 is required for FN polymerization-dependent vascular morphogenesis, both in vitro and in the developing zebrafish embryo. (PMID:27876801)
• Based on these findings, we infer that high PPFIA1 expression might be an independent prognostic indicator of increased metastatic relapse risk in patients with estrogen receptor+/N- breast cancer, but not in estrogen receptor+/N+ or estrogen receptor- patients. (PMID:28720060)
• The results indicate that liprin-alpha1, LL5 and ERC1 define a novel dynamic membrane-less compartment that regulates matrix degradation by affecting invadosome motility. (PMID:29348417)
• liprin-alpha1 as a novel regulator of CD82 (PMID:30005669)
• We found that PPFIA1 and ALG3 were distinctively overexpressed at the mRNA level in HNSCC tissues compared with normal tissues, they had a significant co-occurrence relationship. Patients without both PPFIA1 and ALG3 mRNA expression alterations had better overall survival and disease/progression-free survival compared with patients with both PPFIA1 and ALG3 alterations. (PMID:30805892)
• Quantifying Polarized Extracellular Matrix Secretion in Cultured Endothelial Cells. (PMID:33215388)
• Oligomerized liprin-alpha promotes phase separation of ELKS for compartmentalization of presynaptic active zone proteins. (PMID:33761347)
• High expression of PPFIA1 in human esophageal squamous cell carcinoma correlates with tumor metastasis and poor prognosis. (PMID:37158817)
• Liprin-alpha1 contributes to oncogenic MAPK signaling by counteracting ERK activity. (PMID:38264964)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppfia1	ENSDARG00000098674
mus_musculus	Ppfia1	ENSMUSG00000037519
rattus_norvegicus	Ppfia1	ENSRNOG00000020857
drosophila_melanogaster	Liprin-alpha	FBGN0046704

Paralogs (5): PPFIBP1 (ENSG00000110841), PPFIA2 (ENSG00000139220), PPFIA4 (ENSG00000143847), PPFIBP2 (ENSG00000166387), PPFIA3 (ENSG00000177380)

Protein

Protein identifiers

Liprin-alpha-1 — Q13136 (reviewed: Q13136)

Alternative names: LAR-interacting protein 1, Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1

All UniProt accessions (14): A0A1B0GVT3, A0A2R8Y7R9, A0A3B3ITS2, E9PID5, E9PJZ7, E9PPF6, Q13136, H0YD39, H0YD72, H0YDW2, H0YDZ8, H0YEF9, H0YEK0, H0YF15

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.

Subunit / interactions. Homodimer. Interacts with PTPRF (via D2 domain). Part of a cortical microtubule stabilization complex (CMSC) composed of KANK1, PPFIA1, PPFIBP1, ERC1/ELKS, PHLDB2/LL5beta, CLASPs, KIF21A and possibly additional interactors; within CMSCs KANK1 and PHLDB2/LL5beta seem to be the core components for recruiting microtubule-binding proteins KIF21A and CLASPs, whereas PPFIA1, PPFIBP1 and ERC1/ELKS serve as scaffolds for protein clustering.

Subcellular location. Cytoplasm. Cell cortex.

Tissue specificity. Ubiquitous.

Domain organisation. The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type alpha/alpha. The C-terminal, non-coiled coil regions mediate heterodimerization type alpha/beta and interaction with PTPRD, PTPRF and PTPRS.

Miscellaneous. Due to intron retention.

Similarity. Belongs to the liprin family. Liprin-alpha subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13136-1	1, LAR-interacting protein 1b, LIP.1b, b	yes
Q13136-2	2, LAR-interacting protein 1a, LIP.1a, a

RefSeq proteins (3): NP_001364935, NP_003617, NP_803172 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR029515	Liprin	Family
IPR037620	LIP-1_SAM_1	Domain
IPR037621	LIP-1_SAM_2	Domain
IPR037622	LIP-1_SAM_3	Domain
IPR057892	LIP-1_CC2	Domain

Pfam: PF00536, PF07647, PF25526

UniProt features (49 total): modified residue 13, sequence conflict 9, compositionally biased region 8, coiled-coil region 6, region of interest 5, domain 3, sequence variant 2, chain 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1N7F	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13136-F1	69.56	0.27

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 (13): 150, 230, 239, 242, 244, 448, 666, 668, 693, 761, 763, 1133, 1159

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle
R-HSA-388844	Receptor-type tyrosine-protein phosphatases
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 216 (showing top): GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BROWNE_HCMV_INFECTION_8HR_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, chr11q13, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_CELL_JUNCTION_ORGANIZATION, REACTOME_DOPAMINE_NEUROTRANSMITTER_RELEASE_CYCLE, WANG_LMO4_TARGETS_DN

GO Biological Process (7): cell-matrix adhesion (GO:0007160), signal transduction (GO:0007165), cortical microtubule organization (GO:0043622), synapse organization (GO:0050808), negative regulation of stress fiber assembly (GO:0051497), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), negative regulation of protein localization to plasma membrane (GO:1903077)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), cell cortex (GO:0005938), axon (GO:0030424), protein-containing complex (GO:0032991), presynaptic active zone (GO:0048786), spine apparatus (GO:0097444), Schaffer collateral - CA1 synapse (GO:0098685), dendrite (GO:0030425)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Neurotransmitter release cycle	5
Neuronal System	2
Protein-protein interactions at synapses	1
Transmission across Chemical Synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
neuron projection	2
cell-substrate adhesion	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cortical cytoskeleton organization	1
cytoplasmic microtubule organization	1
cell junction organization	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
regulation of biological quality	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
negative regulation of protein localization to cell periphery	1
negative regulation of protein localization to membrane	1
binding	1
intracellular anatomical structure	1
cell-substrate junction	1
cell periphery	1
cellular_component	1
presynapse	1
endomembrane system	1
dendritic spine	1
membrane-bounded organelle	1
synapse	1
dendritic tree	1

Protein interactions and networks

STRING

1262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPFIA1	PTPRF	P10586	986
PPFIA1	ERC1	Q8IUD2	984
PPFIA1	PTPRS	Q13332	945
PPFIA1	GRIP1	Q9Y3R0	908
PPFIA1	PHLDB2	Q86SQ0	905
PPFIA1	PTPRD	P23468	901
PPFIA1	UNC13B	O14795	858
PPFIA1	KIF1A	Q12756	817
PPFIA1	CLASRP	Q8N2M8	788
PPFIA1	ING4	Q9UNL4	787
PPFIA1	LTO1	Q8WV07	741
PPFIA1	PPFIBP1	Q86W92	716
PPFIA1	GIT1	Q9Y2X7	709
PPFIA1	KANK1	Q14678	669
PPFIA1	MAPK8IP3	Q9UPT6	613

IntAct

302 interactions, top by confidence:

A	B	Type	Score
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
DTNB	DMD	psi-mi:“MI:0914”(association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0914”(association)	0.890
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
PPP2CA	STRN	psi-mi:“MI:0914”(association)	0.840
PPFIA1	DTNB	psi-mi:“MI:0915”(physical association)	0.800
DTNB	PPFIA1	psi-mi:“MI:0915”(physical association)	0.800
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
TXLNA	PPFIA1	psi-mi:“MI:0915”(physical association)	0.740
PPFIA1	CCNH	psi-mi:“MI:0915”(physical association)	0.740
CCNH	PPFIA1	psi-mi:“MI:0915”(physical association)	0.740
PPFIA1	TXLNA	psi-mi:“MI:0915”(physical association)	0.740
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740

BioGRID (336): PPFIA1 (Two-hybrid), PPFIA1 (Two-hybrid), FAM161A (Two-hybrid), TXLNA (Two-hybrid), BRCA1 (Two-hybrid), BRCA1 (Affinity Capture-Western), PPFIA1 (Affinity Capture-MS), PPFIA1 (Affinity Capture-MS), PPFIA1 (Affinity Capture-MS), PPFIA1 (Affinity Capture-MS), PPFIA1 (Two-hybrid), PPFIA1 (Two-hybrid), MBIP (Two-hybrid), PPFIA1 (Affinity Capture-MS), PPFIA1 (Affinity Capture-Western)

ESM2 similar proteins: A0JNT9, A1IH00, A2AUM9, A7MD70, B8JK76, B9EKI3, D3YV10, G9G127, O35550, O35551, P0CB05, P55937, P82094, Q08378, Q08379, Q13136, Q15276, Q3TDD9, Q502I3, Q5BIX7, Q5EE04, Q5T1M5, Q5TZ80, Q5U3A8, Q5U4E6, Q5VU43, Q5ZJ27, Q62839, Q66KE8, Q6NRB0, Q6P132, Q6P3P1, Q6P402, Q6P9Q6, Q6PGZ0, Q6VGS5, Q6ZMI0, Q7SXE4, Q80UF4, Q80YT7

Diamond homologs: A9C3W3, O35711, O75145, O75334, O75335, P60469, Q13136, Q21049, Q5FWS6, Q674X7, Q69ZS8, Q86W92, Q8BSS9, Q8C8U0, Q8ND30, Q91Z79, Q91Z80, Q94071

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PPFIA1	“up-regulates activity”	PTPRF	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	45.9×	2e-09
Activation of BAD and translocation to mitochondria	7	45.5×	8e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	40.2×	2e-08
Signaling by GSK3beta mutants	5	32.5×	8e-06
CTNNB1 S33 mutants aren’t phosphorylated	5	32.5×	8e-06
CTNNB1 S37 mutants aren’t phosphorylated	5	32.5×	8e-06
CTNNB1 S45 mutants aren’t phosphorylated	5	32.5×	8e-06
CTNNB1 T41 mutants aren’t phosphorylated	5	32.5×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	27.5×	3e-06
Golgi to plasma membrane transport	7	26.6×	3e-06
protein targeting	5	12.4×	5e-03
substantia nigra development	5	12.4×	5e-03
exocytosis	9	9.2×	2e-04
protein dephosphorylation	6	9.0×	5e-03
MAPK cascade	7	7.2×	5e-03
intracellular protein localization	10	7.1×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	28
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

4723 predictions. Top by Δscore:

Variant	Effect	Δscore
11:70270910:GCAAG:G	donor_gain	1.0000
11:70270911:CAAGG:C	donor_loss	1.0000
11:70270915:G:GC	donor_loss	1.0000
11:70270916:T:G	donor_loss	1.0000
11:70272170:A:AG	acceptor_gain	1.0000
11:70272170:AAGAT:A	acceptor_gain	1.0000
11:70272171:A:G	acceptor_gain	1.0000
11:70272434:CAGG:C	donor_loss	1.0000
11:70272435:AGG:A	donor_loss	1.0000
11:70272436:GG:G	donor_loss	1.0000
11:70272437:GT:G	donor_loss	1.0000
11:70272438:T:A	donor_loss	1.0000
11:70324391:T:TA	acceptor_gain	1.0000
11:70324399:TAGGA:T	acceptor_gain	1.0000
11:70324400:A:AG	acceptor_gain	1.0000
11:70324400:AG:A	acceptor_gain	1.0000
11:70324400:AGG:A	acceptor_loss	1.0000
11:70324400:AGGAG:A	acceptor_gain	1.0000
11:70324401:G:GG	acceptor_gain	1.0000
11:70324401:GG:G	acceptor_gain	1.0000
11:70324401:GGA:G	acceptor_gain	1.0000
11:70324499:CCAGG:C	donor_gain	1.0000
11:70324500:CAGGG:C	donor_loss	1.0000
11:70324501:AGGGT:A	donor_loss	1.0000
11:70324502:GG:G	donor_gain	1.0000
11:70324503:GG:G	donor_gain	1.0000
11:70324503:GGT:G	donor_loss	1.0000
11:70324504:G:GG	donor_gain	1.0000
11:70324840:A:AG	acceptor_gain	1.0000
11:70324842:TTCA:T	acceptor_loss	1.0000

AlphaMissense

7929 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:70324478:T:C	L114P	1.000
11:70324848:T:C	L123P	1.000
11:70324851:T:C	L124P	1.000
11:70324859:C:G	H127D	1.000
11:70324860:A:C	H127P	1.000
11:70324861:T:A	H127Q	1.000
11:70324861:T:G	H127Q	1.000
11:70324863:T:C	L128S	1.000
11:70324863:T:G	L128W	1.000
11:70324872:T:A	L131H	1.000
11:70324872:T:C	L131P	1.000
11:70324875:T:A	V132D	1.000
11:70324881:G:C	R134T	1.000
11:70324881:G:T	R134M	1.000
11:70324882:G:C	R134S	1.000
11:70324882:G:T	R134S	1.000
11:70324883:C:G	H135D	1.000
11:70324884:A:C	H135P	1.000
11:70324896:T:A	L139H	1.000
11:70324896:T:C	L139P	1.000
11:70324899:G:T	R140M	1.000
11:70324946:A:C	S156R	1.000
11:70324948:C:A	S156R	1.000
11:70324948:C:G	S156R	1.000
11:70324949:G:A	E157K	1.000
11:70324955:G:A	E159K	1.000
11:70324962:T:A	L161Q	1.000
11:70324962:T:C	L161P	1.000
11:70324965:A:T	K162I	1.000
11:70324967:G:C	A163P	1.000

dbSNP variants (sampled 300 via entrez): RS1000032697 (11:70377418 T>C), RS1000040387 (11:70308638 A>C), RS1000061956 (11:70292570 C>G,T), RS1000064902 (11:70334361 C>G,T), RS1000076919 (11:70294423 A>T), RS1000165622 (11:70383594 T>C), RS1000185296 (11:70367718 A>G), RS1000188889 (11:70299879 C>A), RS1000222430 (11:70284411 T>C), RS1000235667 (11:70383248 G>C), RS1000288163 (11:70284633 A>G), RS1000298799 (11:70325390 A>G), RS1000338073 (11:70305578 C>G), RS1000342642 (11:70331167 G>A), RS1000357368 (11:70381009 C>T)

Disease associations

OMIM: gene MIM:611054 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005194_193	Coronary artery disease	2.000000e-06
GCST90002388_542	Lymphocyte count	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs655130	PPFIA1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Ozone	increases oxidation, increases abundance, affects expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases expression	2
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
methylselenic acid	affects expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	increases expression	1
K 7174	increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Arsenic	affects methylation	1

Clinical trials (associated diseases)

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