PPFIA2

Summary

PPFIA2 (PPFI scaffold protein A2, HGNC:9246) is a protein-coding gene on chromosome 12q21.31, encoding Liprin-alpha-2 (O75334). Alters PTPRF cellular localization and induces PTPRF clustering.

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. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein has been shown to bind the calcium/calmodulin-dependent serine protein kinase (MAGUK family) protein (also known as CASK) and proposed to regulate higher-order brain functions in mammals. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8499 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 135 total
• MANE Select transcript: NM_003625

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9246
Approved symbol	PPFIA2
Name	PPFI scaffold protein A2
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000139220
Ensembl biotype	protein_coding
OMIM	603143
Entrez	8499

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 18 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000333447, ENST00000407050, ENST00000443686, ENST00000541017, ENST00000541570, ENST00000545296, ENST00000547180, ENST00000547273, ENST00000547623, ENST00000548453, ENST00000548586, ENST00000548670, ENST00000548790, ENST00000549325, ENST00000549344, ENST00000549396, ENST00000549917, ENST00000550018, ENST00000550359, ENST00000550584, ENST00000550798, ENST00000551147, ENST00000551442, ENST00000551461, ENST00000552006, ENST00000552020, ENST00000552948, ENST00000553058

RefSeq mRNA: 10 — MANE Select: NM_003625 NM_001220473, NM_001220474, NM_001220475, NM_001220476, NM_001220477, NM_001220478, NM_001220479, NM_001220480, NM_001282536, NM_003625

CCDS: CCDS55850, CCDS55851, CCDS55852, CCDS55853, CCDS55854, CCDS55855, CCDS55856, CCDS55857, CCDS59236, CCDS73503

Canonical transcript exons

ENST00000549396 — 33 exons

Exon	Start	End
ENSE00001291264	81284241	81284303
ENSE00001316789	81283010	81283039
ENSE00001373928	81374634	81374768
ENSE00002285402	81257975	81259660
ENSE00002325095	81759280	81759350
ENSE00002396290	81758400	81758507
ENSE00003461223	81261949	81262040
ENSE00003463893	81341078	81341208
ENSE00003475054	81358082	81358217
ENSE00003482583	81457765	81457866
ENSE00003483037	81325777	81325870
ENSE00003493910	81344664	81344693
ENSE00003498521	81439972	81440046
ENSE00003517732	81281257	81281450
ENSE00003523077	81368725	81368856
ENSE00003525772	81362693	81362784
ENSE00003526591	81375796	81375942
ENSE00003560145	81294835	81295035
ENSE00003564368	81266952	81267020
ENSE00003576642	81753973	81754223
ENSE00003585579	81353119	81353339
ENSE00003587327	81384023	81384244
ENSE00003589075	81277317	81277414
ENSE00003602267	81369111	81369194
ENSE00003604112	81299301	81299382
ENSE00003604939	81405787	81405903
ENSE00003620864	81676791	81676844
ENSE00003642678	81339180	81339334
ENSE00003656779	81367108	81367170
ENSE00003663551	81347533	81347770
ENSE00003682606	81267912	81268087
ENSE00003691632	81263231	81263390
ENSE00003694215	81445556	81445720

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 95.96.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5331 / max 1521.4831, expressed in 343 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132313	2.0988	119
132316	1.0274	174
132306	0.9128	76
132320	0.6871	210
132317	0.2559	89
132310	0.1107	22
206822	0.1051	51
132318	0.0987	65
132312	0.0965	28
132319	0.0893	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.96	gold quality
endothelial cell	CL:0000115	94.09	silver quality
prefrontal cortex	UBERON:0000451	92.53	gold quality
ganglionic eminence	UBERON:0004023	92.07	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.10	gold quality
primary visual cortex	UBERON:0002436	91.07	gold quality
superior frontal gyrus	UBERON:0002661	90.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.91	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.82	gold quality
entorhinal cortex	UBERON:0002728	90.65	gold quality
frontal cortex	UBERON:0001870	90.09	gold quality
postcentral gyrus	UBERON:0002581	89.97	gold quality
cerebral cortex	UBERON:0000956	89.93	gold quality
neocortex	UBERON:0001950	89.83	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.78	gold quality
Ammon’s horn	UBERON:0001954	89.47	gold quality
middle temporal gyrus	UBERON:0002771	89.22	gold quality
corpus callosum	UBERON:0002336	89.14	gold quality
ventricular zone	UBERON:0003053	89.01	gold quality
right frontal lobe	UBERON:0002810	88.95	gold quality
telencephalon	UBERON:0001893	88.69	gold quality
temporal lobe	UBERON:0001871	88.59	gold quality
frontal pole	UBERON:0002795	88.53	gold quality
parietal lobe	UBERON:0001872	88.20	gold quality
cingulate cortex	UBERON:0003027	88.15	gold quality
anterior cingulate cortex	UBERON:0009835	88.08	gold quality
occipital lobe	UBERON:0002021	88.04	gold quality
amygdala	UBERON:0001876	87.79	gold quality
nucleus accumbens	UBERON:0001882	87.50	gold quality
forebrain	UBERON:0001890	87.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	89.07
E-CURD-119	yes	40.29
E-ANND-3	no	6.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

133 targeting PPFIA2, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
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-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 5)

• Liprin-alpha2 expression is downregulated by androgens in prostate cancer cells. It might play a role in androgen-responsive human prostate cancer & the loss of this gene expression might be associated with the androgen-independence. (PMID:12119554)
• Liprins can mediate assembly of target proteins into large protein complexes capable of regulating numerous cellular activities. (PMID:21855798)
• 3 genes identified by association study and supported by ocular expression and/or replication, UHRF1BP1L, PTPRR, and PPFIA2, are novel candidates for myopic development within the MYP3 locus that should be further studied. (PMID:23422819)
• mong the 22 cases, we identified PPFIA2 as a novel candidate gene forIntellect Analysis of copy-neutral loss of heterozygosity (CNLOH) detected one case in which the CNLOH regions seem to be significant. The SNP array detected a modest fraction of small causative CNVs, which is explained by the fact that the majority of causative CNVs have larger sizes, and those had been mostly identified in the two previous screenings. (PMID:26740234)
• Liprin alfa 2 gene expression is increased by cannabis use and associated with neuropsychological function. (PMID:30879928)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppfia2	ENSDARG00000013000
mus_musculus	Ppfia2	ENSMUSG00000053825
rattus_norvegicus	Ppfia2	ENSRNOG00000004353
drosophila_melanogaster	Liprin-alpha	FBGN0046704

Paralogs (5): PPFIBP1 (ENSG00000110841), PPFIA1 (ENSG00000131626), PPFIA4 (ENSG00000143847), PPFIBP2 (ENSG00000166387), PPFIA3 (ENSG00000177380)

Protein

Protein identifiers

Liprin-alpha-2 — O75334 (reviewed: O75334)

Alternative names: Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-2

All UniProt accessions (11): O75334, F8VU88, F8VWG6, F8VWR9, F8VYK7, F8W1Y8, G3V200, H0YH95, H0YHJ4, H0YHK3, H0YIJ4

UniProt curated annotations — full annotation on UniProt →

Function. Alters PTPRF cellular localization and induces PTPRF clustering. 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. In neuronal cells, is a scaffolding protein in the dendritic spines which acts as immobile postsynaptic post able to recruit KIF1A-driven dense core vesicles to dendritic spines.

Subunit / interactions. Forms homodimers and heterodimers with liprins-alpha and liprins-beta. Interacts with the second PTPase domain of PTPRD, PTPRF and PTPRS. Interacts with KIF1A; the interaction decreases in presence of calcium.

Subcellular location. Cytoplasm. Cell surface. Cell projection. Dendritic spine.

Tissue specificity. Expressed only in brain.

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.

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

Isoforms (8)

UniProt ID	Names	Canonical?
O75334-1	1	yes
O75334-2	2
O75334-3	3
O75334-4	4
O75334-5	5
O75334-6	6
O75334-7	7
O75334-8	8

RefSeq proteins (10): NP_001207402, NP_001207403, NP_001207404, NP_001207405, NP_001207406, NP_001207407, NP_001207408, NP_001207409, NP_001269465, NP_003616* (*=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 (70 total): helix 27, splice variant 11, modified residue 7, sequence conflict 5, region of interest 5, coiled-coil region 4, compositionally biased region 4, domain 3, strand 2, chain 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7D2E	X-RAY DIFFRACTION	1.7
7D2G	X-RAY DIFFRACTION	1.7
6IUH	X-RAY DIFFRACTION	1.8
3TAC	X-RAY DIFFRACTION	2.2
7D2H	X-RAY DIFFRACTION	2.2
8Z22	X-RAY DIFFRACTION	2.75
3TAD	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75334-F1	66.99	0.26

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 (7): 236, 237, 239, 687, 689, 817, 820

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: 265 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_DENDRITE_DEVELOPMENT, GOBP_VESICLE_LOCALIZATION, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_REGULATION_OF_EXOCYTOSIS, GOCC_CELL_SURFACE, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GGGTGGRR_PAX4_03, SP1_Q2_01, GOBP_CELL_CELL_SIGNALING

GO Biological Process (8): cell-matrix adhesion (GO:0007160), synapse organization (GO:0050808), regulation of dendritic spine development (GO:0060998), regulation of dendritic spine morphogenesis (GO:0061001), dense core granule cytoskeletal transport (GO:0099519), regulation of synaptic vesicle exocytosis (GO:2000300), presynapse organization (GO:0099172), maintenance of postsynaptic density structure (GO:0099562)

GO Molecular Function (3): structural constituent of postsynaptic density (GO:0098919), structural constituent of presynapse (GO:0099181), protein binding (GO:0005515)

GO Cellular Component (14): cytoplasm (GO:0005737), cytosol (GO:0005829), synaptic vesicle (GO:0008021), cell surface (GO:0009986), postsynaptic density (GO:0014069), axon (GO:0030424), presynaptic membrane (GO:0042734), dendritic spine (GO:0043197), presynaptic active zone (GO:0048786), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), cell projection (GO:0042995), synapse (GO:0045202), postsynaptic specialization (GO:0099572)

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	5
presynapse	4
postsynapse	2
cell-substrate adhesion	1
cell junction organization	1
regulation of developmental process	1
dendritic spine development	1
regulation of neuron projection development	1
regulation of anatomical structure morphogenesis	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
axon	1
vesicle cytoskeletal trafficking	1
dense core granule transport	1
synaptic vesicle exocytosis	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
cellular component organization	1
synapse organization	1
maintenance of postsynaptic specialization structure	1
postsynaptic density	1
structural constituent of postsynaptic specialization	1
maintenance of postsynaptic density structure	1
structural constituent of synapse	1
presynapse organization	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
exocytic vesicle	1
asymmetric synapse	1
postsynaptic specialization	1
neuron projection	1
synaptic membrane	1
dendrite	1
neuron spine	1
extracellular vesicle	1
synapse	1
cell junction	1
organelle	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPFIA2	ERC1	Q8IUD2	701
PPFIA2	GIT1	Q9Y2X7	686
PPFIA2	RIMS1	Q86UR5	684
PPFIA2	RIMS2	Q9UQ26	649
PPFIA2	LIN7A	O14910	644
PPFIA2	UNC13A	Q9UPW8	599
PPFIA2	GRIP1	Q9Y3R0	522
PPFIA2	PTPRS	Q13332	483
PPFIA2	ACSS3	Q9H6R3	480
PPFIA2	GRIP2	Q9C0E4	476
PPFIA2	PPFIBP1	Q86W92	469
PPFIA2	RIMBP2	O15034	455
PPFIA2	APBA1	Q02410	452
PPFIA2	GRM1	Q13255	449
PPFIA2	PPFIBP2	Q8ND30	446

IntAct

27 interactions, top by confidence:

A	B	Type	Score
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
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
PPFIA2	SMARCA2	psi-mi:“MI:0915”(physical association)	0.370
PPFIA2	TSC1	psi-mi:“MI:0915”(physical association)	0.370
SETD6	PPFIA2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MED13L	IGKV1-8	psi-mi:“MI:0914”(association)	0.350
CTNNB1	IGLL5	psi-mi:“MI:0914”(association)	0.350
TLK2	IGKV1D-13	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
RIMS1	PSMD12	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
BRK1	KIF5C	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270
PPFIA2	CDC5L	psi-mi:“MI:0915”(physical association)	0.000
CDC5L	PPFIA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): PPFIA2 (Two-hybrid), PPFIA3 (Two-hybrid), PPFIBP1 (Two-hybrid), PPFIA2 (Two-hybrid), PPFIA2 (Affinity Capture-RNA), PPFIA2 (Affinity Capture-MS), PPFIA2 (Proximity Label-MS), PPFIA2 (Affinity Capture-MS), GIT1 (Two-hybrid), ERC2 (Two-hybrid), GIT1 (Reconstituted Complex), ERC2 (Reconstituted Complex), ERC2 (Affinity Capture-Western), PPFIA2 (Protein-RNA), PPFIA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GXY6, A0A8I3QA39, A0M8S4, A1YB07, A2A6T1, B6RSP1, B8A5S6, E1BEQ5, F1MRK3, G3V735, O75334, O75335, O94876, P39880, P53564, P53565, Q01664, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07E41, Q09YG9, Q09YI1, Q09YJ3, Q09YK4, Q09YM8, Q108T9, Q13136, Q2IBF8, Q2QLF8, Q3UIL6, Q5RDH2, Q5U4W1, Q69ZZ6, Q6DIS8, Q6IQ23, Q6NZT2, Q6P402, Q8BHS8

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
“R2SP co-chaperone”	“up-regulates quantity by stabilization”	PPFIA2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

7816 predictions. Top by Δscore:

Variant	Effect	Δscore
12:81268083:CACGT:C	acceptor_gain	1.0000
12:81268085:CGT:C	acceptor_gain	1.0000
12:81268088:C:CC	acceptor_gain	1.0000
12:81294829:A:AC	donor_gain	1.0000
12:81294830:C:CC	donor_gain	1.0000
12:81294830:CTCA:C	donor_gain	1.0000
12:81294831:T:TC	donor_loss	1.0000
12:81294832:CA:C	donor_loss	1.0000
12:81294833:A:AC	donor_gain	1.0000
12:81294833:ACAG:A	donor_loss	1.0000
12:81294834:C:CT	donor_gain	1.0000
12:81294834:CA:C	donor_gain	1.0000
12:81294834:CAG:C	donor_gain	1.0000
12:81294834:CAGT:C	donor_gain	1.0000
12:81294834:CAGTT:C	donor_gain	1.0000
12:81295031:CAAAG:C	acceptor_gain	1.0000
12:81295036:C:CC	acceptor_gain	1.0000
12:81325774:TA:T	donor_loss	1.0000
12:81325775:A:AC	donor_gain	1.0000
12:81325776:C:A	donor_loss	1.0000
12:81325776:C:CA	donor_gain	1.0000
12:81325776:CT:C	donor_gain	1.0000
12:81325776:CTT:C	donor_gain	1.0000
12:81325868:CTC:C	acceptor_gain	1.0000
12:81337980:AATT:A	donor_gain	1.0000
12:81337983:T:TA	donor_gain	1.0000
12:81339174:A:AC	donor_gain	1.0000
12:81339175:C:CC	donor_gain	1.0000
12:81339178:A:AC	donor_gain	1.0000
12:81339179:C:CC	donor_gain	1.0000

AlphaMissense

8222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:81267991:C:T	G1136D	1.000
12:81267992:C:G	G1136R	1.000
12:81268076:A:G	W1108R	1.000
12:81268076:A:T	W1108R	1.000
12:81277397:C:T	G1077E	1.000
12:81277398:C:G	G1077R	1.000
12:81277398:C:T	G1077R	1.000
12:81281293:A:G	L1059P	1.000
12:81281308:A:G	L1054P	1.000
12:81281329:T:A	D1047V	1.000
12:81281383:A:G	L1029P	1.000
12:81281383:A:T	L1029H	1.000
12:81281387:A:G	W1028R	1.000
12:81281387:A:T	W1028R	1.000
12:81281400:C:A	W1023C	1.000
12:81281400:C:G	W1023C	1.000
12:81281402:A:G	W1023R	1.000
12:81281402:A:T	W1023R	1.000
12:81294869:A:G	L964P	1.000
12:81294887:A:T	I958N	1.000
12:81294893:A:G	L956S	1.000
12:81294899:A:G	L954P	1.000
12:81294899:A:T	L954H	1.000
12:81294901:T:A	K953N	1.000
12:81294901:T:G	K953N	1.000
12:81294908:C:G	R951P	1.000
12:81294909:G:T	R951S	1.000
12:81294929:C:T	G944E	1.000
12:81294944:A:C	I939S	1.000
12:81294944:A:G	I939T	1.000

dbSNP variants (sampled 300 via entrez): RS1000006885 (12:81465717 A>G), RS1000011712 (12:81627197 T>C,G), RS1000012493 (12:81424810 G>A), RS1000016981 (12:81758770 C>T), RS1000027941 (12:81276866 T>A,C), RS1000029064 (12:81287504 G>C,T), RS1000037183 (12:81380314 T>A), RS1000040525 (12:81546701 A>C), RS1000041801 (12:81455712 G>A,T), RS1000042009 (12:81424569 G>A), RS1000052222 (12:81548694 A>C), RS1000052368 (12:81725989 T>C), RS1000056115 (12:81538547 T>A), RS1000059454 (12:81706824 T>C), RS1000077573 (12:81370192 A>C)

Disease associations

OMIM: gene MIM:603143 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001657_3	Schizophrenia	4.000000e-06
GCST002618_2	Age-related cataracts (age at onset)	6.000000e-07
GCST003121_7	Alcohol dependence	4.000000e-06
GCST003262_483	Post bronchodilator FEV1	4.000000e-06
GCST003818_14	Resting heart rate	5.000000e-10
GCST005851_21	Delirium	3.000000e-06
GCST008153_40	Lean body mass	8.000000e-06
GCST012490_332	Femur bone mineral density x serum urate levels interaction	2.000000e-09
GCST012490_410	Femur bone mineral density x serum urate levels interaction	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004314	forced expiratory volume
EFO:0004995	lean body mass
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation, affects methylation, decreases expression	3
methyleugenol	decreases expression	1
sodium arsenite	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
entinostat	decreases expression	1
Acetaminophen	increases expression	1
Cannabidiol	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice