PPFIA3

Summary

PPFIA3 (PPFI scaffold protein A3, HGNC:9247) is a protein-coding gene on chromosome 19q13.33, encoding Liprin-alpha-3 (O75145). 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. Liprin family protein has been shown to localize phosphatase LAR to cell focal adhesions and may be involved in the molecular organization of presynaptic active zones.

Source: NCBI Gene 8541 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 200 total — 4 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 114
• MANE Select transcript: NM_003660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9247
Approved symbol	PPFIA3
Name	PPFI scaffold protein A3
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0654, LPNA3, MGC126567, MGC126569
Ensembl gene	ENSG00000177380
Ensembl biotype	protein_coding
OMIM	603144
Entrez	8541

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 retained_intron, 6 protein_coding, 1 nonsense_mediated_decay

ENST00000334186, ENST00000421230, ENST00000602351, ENST00000602492, ENST00000602509, ENST00000602655, ENST00000602716, ENST00000602726, ENST00000602783, ENST00000602800, ENST00000602848, ENST00000602897, ENST00000602905, ENST00000867300

RefSeq mRNA: 1 — MANE Select: NM_003660 NM_003660

CCDS: CCDS12758

Canonical transcript exons

ENST00000334186 — 30 exons

Exon	Start	End
ENSE00001338643	49138205	49138427
ENSE00001338687	49127859	49128113
ENSE00001338689	49119544	49119722
ENSE00001390108	49128367	49128468
ENSE00003436008	49150236	49151026
ENSE00003464005	49141420	49141513
ENSE00003466122	49129993	49130067
ENSE00003474132	49145943	49146005
ENSE00003492662	49129380	49129454
ENSE00003492842	49130378	49130599
ENSE00003499884	49146166	49146192
ENSE00003521768	49134034	49134165
ENSE00003535656	49149257	49149325
ENSE00003549539	49134836	49134915
ENSE00003560881	49133237	49133371
ENSE00003562429	49148083	49148258
ENSE00003567469	49142034	49142115
ENSE00003568403	49128848	49129012
ENSE00003568611	49136724	49136911
ENSE00003593618	49150080	49150151
ENSE00003605586	49142804	49143004
ENSE00003607458	49133796	49133879
ENSE00003626004	49148666	49148763
ENSE00003626790	49134639	49134701
ENSE00003660691	49149547	49149718
ENSE00003662783	49139668	49139831
ENSE00003662857	49148993	49149168
ENSE00003665753	49139961	49140088
ENSE00003677256	49135779	49135923
ENSE00003677541	49133001	49133147

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 95.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1491 / max 108.3331, expressed in 993 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176939	2.0322	599
176938	0.9776	404
176942	0.7973	297
176936	0.6684	211
176943	0.5674	284
176940	0.5261	240
176941	0.2268	58
176935	0.1833	75
176937	0.1701	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.96	gold quality
cerebellar hemisphere	UBERON:0002245	95.69	gold quality
right frontal lobe	UBERON:0002810	95.65	gold quality
cerebellar cortex	UBERON:0002129	95.57	gold quality
cingulate cortex	UBERON:0003027	93.96	gold quality
anterior cingulate cortex	UBERON:0009835	93.93	gold quality
cerebellum	UBERON:0002037	93.73	gold quality
prefrontal cortex	UBERON:0000451	93.58	gold quality
adenohypophysis	UBERON:0002196	93.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.84	gold quality
mucosa of transverse colon	UBERON:0004991	92.09	gold quality
skin of leg	UBERON:0001511	92.06	gold quality
amygdala	UBERON:0001876	92.04	gold quality
pituitary gland	UBERON:0000007	91.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.74	gold quality
neocortex	UBERON:0001950	91.30	gold quality
frontal cortex	UBERON:0001870	91.11	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.91	gold quality
skin of abdomen	UBERON:0001416	90.78	gold quality
lower esophagus mucosa	UBERON:0035834	90.11	gold quality
frontal pole	UBERON:0002795	89.90	gold quality
paraflocculus	UBERON:0005351	89.78	gold quality
cortical plate	UBERON:0005343	89.76	gold quality
cerebral cortex	UBERON:0000956	89.49	gold quality
primary visual cortex	UBERON:0002436	89.34	gold quality
nucleus accumbens	UBERON:0001882	88.59	gold quality
forebrain	UBERON:0001890	88.36	gold quality
telencephalon	UBERON:0001893	88.32	gold quality
brain	UBERON:0000955	88.15	gold quality
hypothalamus	UBERON:0001898	88.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting PPFIA3, 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-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-6773-5P	97.04	64.30	595

Literature-anchored findings (GeneRIF, showing 2)

• Results found that OSR2, VAV3, and PPFIA3 were significantly hypermethylated in gastric cancer (GC) patients offering a good alternative in a simple, promising, and noninvasive detection of GC. (PMID:27143812)
• A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3. (PMID:38181735)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppfia3	ENSDARG00000077053
mus_musculus	Ppfia3	ENSMUSG00000003863
rattus_norvegicus	Ppfia3	ENSRNOG00000020731
drosophila_melanogaster	Liprin-alpha	FBGN0046704

Paralogs (5): PPFIBP1 (ENSG00000110841), PPFIA1 (ENSG00000131626), PPFIA2 (ENSG00000139220), PPFIA4 (ENSG00000143847), PPFIBP2 (ENSG00000166387)

Protein

Protein identifiers

Liprin-alpha-3 — O75145 (reviewed: O75145)

Alternative names: Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-3

All UniProt accessions (5): O75145, A0A0C4DGR7, A0A0C4DGR8, R4GN36, R4GNF1

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. Forms homodimers and heterodimers with liprins-alpha and liprins-beta. Interacts with the second PTPase domain of PTPRD, PTPRF and PTPRS. Binds RIMS1, RIMS2, RIMS3 and RIMS4.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Predominantly expressed in brain. Also detected in sperm (at protein level).

Disease relevance. Paul-Chao neurodevelopmental syndrome (NEDPACH) [MIM:621122] An autosomal dominant disorder characterized by global developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, behavioral abnormalities including autistic features, and epilepsy with reduced penetrance. The disease is caused by variants affecting the gene represented in this entry.

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. May be due to exon skipping.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O75145-1	1	yes
O75145-2	2

RefSeq proteins (1): NP_003651* (*=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 (53 total): modified residue 15, sequence variant 15, compositionally biased region 7, region of interest 5, coiled-coil region 4, domain 3, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75145-F1	70.27	0.30

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 (15): 17, 142, 207, 431, 508, 640, 645, 668, 683, 714, 737, 792, 794, 1123, 1164

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: 397 (showing top): RNGTGGGC_UNKNOWN, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SHORT_TERM_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, GOBP_EXOCYTOSIS, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_205, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_VESICLE_DOCKING_INVOLVED_IN_EXOCYTOSIS, FOSTER_TOLERANT_MACROPHAGE_DN, REACTOME_DOPAMINE_NEUROTRANSMITTER_RELEASE_CYCLE

GO Biological Process (5): neurotransmitter secretion (GO:0007269), obsolete synaptic vesicle docking (GO:0016081), regulation of short-term neuronal synaptic plasticity (GO:0048172), synapse organization (GO:0050808), synaptic vesicle exocytosis (GO:0016079)

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

GO Cellular Component (9): acrosomal vesicle (GO:0001669), cytosol (GO:0005829), presynaptic active zone (GO:0048786), presynaptic active zone cytoplasmic component (GO:0098831), epididymosome (GO:0098875), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

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
presynapse	3
cellular anatomical structure	3
establishment of localization in cell	2
signal release from synapse	2
cytoplasm	2
neurotransmitter transport	1
chemical synaptic transmission	1
regulation of neuronal synaptic plasticity	1
cell junction organization	1
neurotransmitter secretion	1
regulated exocytosis	1
vesicle-mediated transport in synapse	1
synaptic vesicle cycle	1
binding	1
secretory granule	1
presynaptic active zone	1
cell cortex region	1
microvesicle	1
synapse	1
intracellular anatomical structure	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPFIA3	ERC1	Q8IUD2	957
PPFIA3	UNC13B	O14795	920
PPFIA3	PTPRF	P10586	910
PPFIA3	GRIP1	Q9Y3R0	769
PPFIA3	CLASRP	Q8N2M8	739
PPFIA3	PTPRS	Q13332	723
PPFIA3	GIT1	Q9Y2X7	723
PPFIA3	KIF1A	Q12756	716
PPFIA3	RIMS1	Q86UR5	664
PPFIA3	MAPK8IP3	Q9UPT6	649
PPFIA3	APBA1	Q02410	615
PPFIA3	PTPRD	P23468	604
PPFIA3	GIT2	Q14161	582
PPFIA3	PHLDB2	Q86SQ0	576
PPFIA3	RIMBP2	O15034	566

IntAct

55 interactions, top by confidence:

A	B	Type	Score
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
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
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
MED4	MED14	psi-mi:“MI:0914”(association)	0.740
PPP2R1A	PPFIA3	psi-mi:“MI:0914”(association)	0.670
PPFIA3	PPP1R13B	psi-mi:“MI:0915”(physical association)	0.560
SORBS3	PPFIA3	psi-mi:“MI:0915”(physical association)	0.560
PPFIA3	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
PPFIA3	CBY2	psi-mi:“MI:0915”(physical association)	0.560
PPFIA3	DISC1	psi-mi:“MI:0915”(physical association)	0.560
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
GPS2	DCTN6	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
PPP2CA	SMCO3	psi-mi:“MI:0914”(association)	0.420
PPFIA3	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
PPFIA3	S100A10	psi-mi:“MI:0915”(physical association)	0.400
	RAP1BL	psi-mi:“MI:0915”(physical association)	0.400
CFAP263	PPFIA3	psi-mi:“MI:0915”(physical association)	0.400
PPP2CA	ENSA	psi-mi:“MI:0914”(association)	0.350
PPP2CB	ENSA	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), PPFIA3 (Two-hybrid), PPFIA3 (Two-hybrid), PPFIA3 (Two-hybrid), PPFIA3 (Two-hybrid), PPFIBP1 (Two-hybrid), PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), PPFIA3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I3QA39, A1YB07, A2A6T1, A2A9T0, A2AHG0, A5PKL7, A6NKD9, A7MCY6, B8A5S6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O60299, O75145, O94964, P60469, Q1LZH7, Q3LUD4, Q3UIL6, Q499E4, Q5JTD0, Q5RCR6, Q5XIA0, Q62036, Q63ZY3, Q6DG50, Q6IQ23, Q6NZT2, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IY63, Q8K1Q4, Q8K371

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	19.4×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	9
Uncertain significance	141
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2429368	NM_003660.4(PPFIA3):c.2350C>T (p.Arg784Trp)	Pathogenic
2663924	NM_003660.4(PPFIA3):c.2706dup (p.Ser903fs)	Pathogenic
3024544	NM_003660.4(PPFIA3):c.586_587del (p.Leu196fs)	Pathogenic
3572563	NM_003660.4(PPFIA3):c.2332C>T (p.Arg778Ter)	Pathogenic
1992425	NM_003660.4(PPFIA3):c.3307del (p.Glu1103fs)	Likely pathogenic
2429366	NM_003660.4(PPFIA3):c.1675C>T (p.Arg559Trp)	Likely pathogenic
2429367	NM_003660.4(PPFIA3):c.1285C>T (p.Arg429Trp)	Likely pathogenic
2430187	NM_003660.4(PPFIA3):c.1638G>T (p.Trp546Cys)	Likely pathogenic
2444005	NM_003660.4(PPFIA3):c.1492C>T (p.Arg498Trp)	Likely pathogenic
2582700	NM_003660.4(PPFIA3):c.943G>T (p.Ala315Ser)	Likely pathogenic
2583123	NM_003660.4(PPFIA3):c.2609T>A (p.Ile870Asn)	Likely pathogenic
3369138	NM_003660.4(PPFIA3):c.241-1G>A	Likely pathogenic
3764230	NM_003660.4(PPFIA3):c.2374del (p.Thr792fs)	Likely pathogenic

SpliceAI

4551 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49127854:CGCAG:C	acceptor_loss	1.0000
19:49127855:GCAGG:G	acceptor_loss	1.0000
19:49127856:CA:C	acceptor_loss	1.0000
19:49127857:A:C	acceptor_loss	1.0000
19:49128093:C:G	donor_gain	1.0000
19:49128366:GGA:G	acceptor_gain	1.0000
19:49128465:GCGG:G	donor_gain	1.0000
19:49128467:GG:G	donor_gain	1.0000
19:49128467:GGGT:G	donor_loss	1.0000
19:49128468:GG:G	donor_gain	1.0000
19:49128469:G:GG	donor_gain	1.0000
19:49128469:GTG:G	donor_loss	1.0000
19:49128470:T:G	donor_loss	1.0000
19:49128824:T:A	acceptor_gain	1.0000
19:49128832:T:TA	acceptor_gain	1.0000
19:49128835:C:A	acceptor_gain	1.0000
19:49128837:T:TA	acceptor_gain	1.0000
19:49128839:T:TA	acceptor_gain	1.0000
19:49128843:TGCAG:T	acceptor_loss	1.0000
19:49128845:CA:C	acceptor_loss	1.0000
19:49128846:A:AG	acceptor_gain	1.0000
19:49128846:A:C	acceptor_loss	1.0000
19:49128846:AGCT:A	acceptor_gain	1.0000
19:49128847:G:A	acceptor_loss	1.0000
19:49128847:G:GC	acceptor_gain	1.0000
19:49128847:GC:G	acceptor_gain	1.0000
19:49128847:GCT:G	acceptor_gain	1.0000
19:49128847:GCTG:G	acceptor_gain	1.0000
19:49128847:GCTGC:G	acceptor_gain	1.0000
19:49129009:GAAG:G	donor_gain	1.0000

AlphaMissense

7701 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49128443:T:C	L106P	1.000
19:49128455:G:C	R110P	1.000
19:49128852:T:C	L116P	1.000
19:49128855:T:C	L117P	1.000
19:49128864:T:C	L120P	1.000
19:49128873:T:C	L123P	1.000
19:49128897:T:C	L131P	1.000
19:49128963:T:C	L153P	1.000
19:49128972:T:C	L156P	1.000
19:49128981:T:C	L159P	1.000
19:49128983:T:C	F160L	1.000
19:49128985:C:A	F160L	1.000
19:49128985:C:G	F160L	1.000
19:49128992:C:G	H163D	1.000
19:49129002:T:C	L166P	1.000
19:49129393:T:C	L174P	1.000
19:49133032:G:C	R304P	1.000
19:49133044:T:C	L308P	1.000
19:49133292:T:C	L361P	1.000
19:49133336:G:C	A376P	1.000
19:49133343:T:C	L378P	1.000
19:49133352:G:C	R381P	1.000
19:49133364:T:C	L385P	1.000
19:49133830:T:C	L399P	1.000
19:49133851:T:C	L406P	1.000
19:49133872:T:C	L413P	1.000
19:49134044:G:C	R419P	1.000
19:49134077:T:C	L430P	1.000
19:49134098:T:C	L437P	1.000
19:49134101:T:C	L438P	1.000

dbSNP variants (sampled 300 via entrez): RS1000029134 (19:49118920 C>G,T), RS1000032768 (19:49133690 T>G), RS1000044942 (19:49147580 G>A,T), RS1000133101 (19:49139972 C>T), RS1000186631 (19:49122549 C>T), RS1000223420 (19:49129687 A>G,T), RS1000273117 (19:49141937 A>G), RS1000353470 (19:49136351 C>G,T), RS1000384150 (19:49134089 T>C,G), RS1000394593 (19:49127246 G>C,T), RS1000582377 (19:49144584 T>C), RS1000727029 (19:49125924 AT>A,ATT), RS1000805116 (19:49123095 C>T), RS1000973609 (19:49146810 A>G), RS1001038275 (19:49144391 G>T)

Disease associations

OMIM: gene MIM:603144 | disease phenotypes: MIM:621122

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	Autosomal dominant
PPFIA3-related neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (2): PPFIA3-related neurodevelopmental disorder (MONDO:1040014), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

114 total (30 of 114 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000062	Ambiguous genitalia
HP:0000083	Renal insufficiency
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000325	Triangular face
HP:0000338	Hypomimic face
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000527	Long eyelashes
HP:0000540	Hypermetropia
HP:0000565	Esotropia
HP:0000570	Abnormal saccadic eye movements
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000687	Widely spaced teeth

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010676_10	Leukoderma in response to rhododendrol	9.000000e-06
GCST010988_312	Adult body size	4.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects response to substance, affects expression	1
beta-lapachone	decreases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Cocaine	increases expression	1
Diazinon	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder