PHF12

Summary

PHF12 (PHD finger protein 12, HGNC:20816) is a protein-coding gene on chromosome 17q11.2, encoding PHD finger protein 12 (Q96QT6). Transcriptional repressor acting as key scaffolding subunit of SIN3 complexes which contributes to complex assembly by contacting each core subunit domain, stabilizes the complex and constitutes the substrate receptor by recruiting the H3 histone tail. It is a selective cancer dependency (DepMap: 56.0% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

Enables phosphatidylinositol binding activity and transcription corepressor activity. Involved in negative regulation of DNA-templated transcription. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of Sin3-type complex and transcription repressor complex.

Source: NCBI Gene 57649 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 103 total
• Cancer dependency (DepMap): dependent in 56.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001033561

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20816
Approved symbol	PHF12
Name	PHD finger protein 12
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	PF1, KIAA1523
Ensembl gene	ENSG00000109118
Ensembl biotype	protein_coding
OMIM	618645
Entrez	57649

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000268756, ENST00000332830, ENST00000378879, ENST00000483934, ENST00000577226, ENST00000578900, ENST00000579036, ENST00000579563, ENST00000582436, ENST00000582655, ENST00000582853, ENST00000583524, ENST00000583747, ENST00000584236, ENST00000584685, ENST00000584822, ENST00000589176, ENST00000903933, ENST00000930975

RefSeq mRNA: 3 — MANE Select: NM_001033561 NM_001033561, NM_001290131, NM_020889

CCDS: CCDS11247, CCDS32598, CCDS76981

Canonical transcript exons

ENST00000332830 — 15 exons

Exon	Start	End
ENSE00001311062	28905250	28906517
ENSE00003462790	28913879	28914037
ENSE00003486424	28907590	28907672
ENSE00003490152	28950065	28950246
ENSE00003493615	28917285	28917449
ENSE00003496154	28926991	28927063
ENSE00003496385	28919143	28919275
ENSE00003526635	28911112	28911237
ENSE00003557247	28912482	28913277
ENSE00003583399	28921688	28921808
ENSE00003584175	28923909	28924302
ENSE00003604648	28906856	28906994
ENSE00003633527	28908783	28908881
ENSE00003787798	28910226	28910369
ENSE00003845929	28950895	28951518

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 94.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2685 / max 377.9102, expressed in 1804 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165103	11.0701	1786
165102	3.5985	1410
165100	0.8555	328
165099	0.3935	130
165101	0.2757	84
165098	0.0752	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.77	gold quality
granulocyte	CL:0000094	94.12	gold quality
bone marrow cell	CL:0002092	93.73	gold quality
stromal cell of endometrium	CL:0002255	92.59	gold quality
cortical plate	UBERON:0005343	91.72	gold quality
spleen	UBERON:0002106	91.70	gold quality
right lung	UBERON:0002167	90.92	gold quality
blood	UBERON:0000178	90.90	gold quality
vermiform appendix	UBERON:0001154	90.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.48	gold quality
mucosa of stomach	UBERON:0001199	90.35	gold quality
ganglionic eminence	UBERON:0004023	90.33	gold quality
right lobe of thyroid gland	UBERON:0001119	90.20	gold quality
prostate gland	UBERON:0002367	90.19	gold quality
left uterine tube	UBERON:0001303	90.15	gold quality
leukocyte	CL:0000738	89.91	gold quality
body of uterus	UBERON:0009853	89.83	gold quality
left lobe of thyroid gland	UBERON:0001120	89.80	gold quality
body of pancreas	UBERON:0001150	89.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.69	gold quality
ventricular zone	UBERON:0003053	89.64	gold quality
monocyte	CL:0000576	89.61	gold quality
tibial artery	UBERON:0007610	89.53	gold quality
popliteal artery	UBERON:0002250	89.52	gold quality
metanephros cortex	UBERON:0010533	89.48	gold quality
thyroid gland	UBERON:0002046	89.34	gold quality
upper lobe of left lung	UBERON:0008952	89.13	gold quality
right coronary artery	UBERON:0001625	89.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.06	gold quality
lymph node	UBERON:0000029	89.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting PHF12, 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-513A-5P	100.00	69.77	2465
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-4788	95.82	66.85	73

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 56.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer. (PMID:39075515)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	phf12a	ENSDARG00000074303
danio_rerio	phf12b	ENSDARG00000075509
mus_musculus	Phf12	ENSMUSG00000037791
rattus_norvegicus	Phf12	ENSRNOG00000009566
drosophila_melanogaster	CG3815	FBGN0029861

Paralogs (5): ZMYND11 (ENSG00000015171), PHF21B (ENSG00000056487), ZMYND8 (ENSG00000101040), PHF21A (ENSG00000135365), AIRE (ENSG00000160224)

Protein

Protein identifiers

PHD finger protein 12 — Q96QT6 (reviewed: Q96QT6)

Alternative names: PHD factor 1

All UniProt accessions (11): Q96QT6, C9J9G2, J3QQU3, K7EJ43, K7EJN7, K7EJY3, K7EMX6, K7ENU0, K7EPF7, K7EQP5, K7ERZ4

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor acting as key scaffolding subunit of SIN3 complexes which contributes to complex assembly by contacting each core subunit domain, stabilizes the complex and constitutes the substrate receptor by recruiting the H3 histone tail. SIN3 complexes are composed of a SIN3 scaffold subunit, one catalytic core (HDAC1 or HDAC2) and 2 chromatin targeting modules. SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2. SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription. May also repress transcription in a SIN3A-independent manner through recruitment of functional TLE5 complexes to DNA. May also play a role in ribosomal biogenesis.

Subunit / interactions. Component of SIN3 complexes. Interacts with SIN3A in a complex composed of HDAC1, SAP30 and SIN3A. Component of the SIN3B complex, which includes SIN3B, HDAC2 or HDAC1, PHF12 and MORF4L1; interacts directly with all subunits. Interacts with TLE5.

Subcellular location. Nucleus.

Domain organisation. In the context of the SIN3B complex, the PHD-type 1 Zinc finger delivers the H3 substrate to the HDAC active site. The atypical PHD-type 2 Zinc finger has a structural role raher than a substrate recruitment role, wedged betweem SIN3B amd the HDAC and stabilizing the SIN3B:HDAC2 interaction. Also interacts with SIN3B through the SIN3 interacting domain 2 (SID2). Interacts with MORF4L1 through PHD-type 1 in a SIN3 interacting domain 1 (SID1)-dependent manner. The polybasic region (PBR) is responsive to the binding to phosphoinositides (PtdInsPs).

Miscellaneous. Incomplete sequence.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96QT6-1	1	yes
Q96QT6-2	2
Q96QT6-3	3
Q96QT6-4	4
Q96QT6-5	5

RefSeq proteins (3): NP_001028733, NP_001277060, NP_065940 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR001965	Znf_PHD	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR031966	PHF12_MRG-bd	Domain
IPR038098	PHF12_MRG-bd_sf	Homologous_superfamily
IPR042163	PHF12	Family

Pfam: PF00628, PF16737

UniProt features (75 total): binding site 13, region of interest 12, strand 11, helix 7, modified residue 6, splice variant 6, cross-link 5, turn 5, compositionally biased region 4, zinc finger region 2, chain 1, domain 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8BPB	ELECTRON MICROSCOPY	2.8
8BPC	ELECTRON MICROSCOPY	2.8
8C60	ELECTRON MICROSCOPY	3.4
8BPA	ELECTRON MICROSCOPY	3.7
2L9S	SOLUTION NMR
2LKM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QT6-F1	55.98	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (13): 59; 61; 62; 79; 82; 274; 277; 289; 292; 297; 300; 315 …

Post-translational modifications (11): 131, 134, 555, 557, 570, 671, 467, 900, 973, 987, 991

Mutagenesis-validated functional residues (1):

Position	Phenotype
57	loss of binding to histone h3 tail.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 244 (showing top): RNGTGGGC_UNKNOWN, PAX4_01, CCAWYNNGAAR_UNKNOWN, GGGNRMNNYCAT_UNKNOWN, LFA1_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GGGTGGRR_PAX4_03, chr17q11, SRF_Q5_01, GGGCATT_MIR365, SRF_C, CATTTCA_MIR203, E2F_Q3, OCT1_03

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (6): transcription corepressor binding (GO:0001222), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription repressor complex (GO:0017053), Sin3-type complex (GO:0070822)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator binding	1
transcription coregulator activity	1
transition metal ion binding	1
anion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
transcription regulator complex	1
histone deacetylase complex	1
nuclear chromosome	1
chromatin	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHF12	MORF4L1	Q9UBU8	882
PHF12	EMSY	Q7Z589	785
PHF12	STK39	Q9UEW8	780
PHF12	MAP4K2	Q12851	728
PHF12	GATAD1	Q8WUU5	699
PHF12	PF4	P02776	693
PHF12	OXSR1	O95747	693
PHF12	KDM5A	P29375	676
PHF12	SIN3B	O75182	668
PHF12	BRMS1L	Q5PSV4	663
PHF12	STK24	Q9Y6E0	659
PHF12	BRMS1	Q9HCU9	652
PHF12	HDAC1	Q13547	650
PHF12	SIN3A	Q96ST3	640
PHF12	F2	P00734	596

IntAct

73 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
MORF4L1	PHF12	psi-mi:“MI:0407”(direct interaction)	0.740
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
MORF4L2	YEATS4	psi-mi:“MI:0914”(association)	0.640
KDM5A	SIN3B	psi-mi:“MI:0914”(association)	0.640
SIN3B	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
GATAD1	SIN3B	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
PHF12	SHANK3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (180): PHF12 (Two-hybrid), PHF12 (Protein-peptide), PHF12 (Affinity Capture-MS), PHF12 (Affinity Capture-MS), PHF12 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), KDM5A (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), S100A4 (Affinity Capture-MS), MORF4L2 (Affinity Capture-MS), MORF4L1 (Affinity Capture-MS), SIN3B (Affinity Capture-MS), C11orf30 (Affinity Capture-MS), PHF12 (Affinity Capture-MS)

ESM2 similar proteins: A0JMZ4, A2AWL7, A8MW92, B0S6S9, D3Z3C6, E7FAP1, F1QB81, O60284, P0C2N5, P29352, P52551, P62287, P62288, P62289, P62296, Q13029, Q28DE6, Q3U285, Q3U8K7, Q4FZB7, Q4V7H1, Q5EXX3, Q5RJX8, Q5SPL2, Q5SW75, Q5U3H2, Q5ZJK5, Q5ZLE9, Q63755, Q6GP17, Q6KAQ7, Q6NRK3, Q6PCB5, Q6PJP8, Q76I76, Q76I79, Q80TY4, Q86XD8, Q8BLG0, Q8CCJ9

Diamond homologs: A1YVX4, A2A8L1, A2AUY4, A2BIL7, A6H619, A7E320, A8DZJ1, A9LMC0, B6CHA3, B7ZS37, B9RU15, C4QVX6, D3ZD32, E7EZF3, F4I240, F4JYC8, F4KE59, F6UA42, G5EBZ4, O43918, O88379, O94400, O97159, P29375, P41229, P41230, P46605, P47156, P48786, P56163, P58268, P58269, P58270, Q04996, Q09477, Q12830, Q12873, Q14839, Q23541, Q23590

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PHF12	“form complex”	Sin3B_complex	binding
PHF12	“up-regulates activity”	TLE4	binding
PHF12	“up-regulates activity”	TLE5	binding
PHF12	“up-regulates activity”	TLE6	binding
PHF12	“up-regulates activity”	TLE2	binding
PHF12	“up-regulates activity”	TLE3	binding
PHF12	“up-regulates activity”	TLE1	binding
PHF12	“up-regulates activity”	SIN3A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	14.9×	9e-04
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	6	14.4×	3e-04
NuRD complex assembly	5	14.4×	1e-03
Interaction of NuRD complexes with transcription factors	5	12.9×	1e-03
Negative Regulation of CDH1 Gene Transcription	5	12.3×	2e-03
Chromatin organization	7	11.7×	3e-04
Activation of anterior HOX genes in hindbrain development during early embryogenesis	6	11.2×	8e-04
Chromatin modifying enzymes	7	10.3×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	14	15.7×	3e-11
chromatin organization	6	9.2×	2e-03
transcription by RNA polymerase II	8	8.7×	3e-04
positive regulation of gene expression	8	4.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1667 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28913874:CTCA:C	donor_loss	1.0000
17:28913875:TCA:T	donor_loss	1.0000
17:28913876:CAC:C	donor_loss	1.0000
17:28913878:C:A	donor_loss	1.0000
17:28913878:CCT:C	donor_gain	1.0000
17:28914038:C:CA	acceptor_loss	1.0000
17:28917280:CTCA:C	donor_loss	1.0000
17:28917283:A:AC	donor_gain	1.0000
17:28917284:C:CA	donor_gain	1.0000
17:28917284:CCTT:C	donor_gain	1.0000
17:28917445:TTCAG:T	acceptor_gain	1.0000
17:28917446:TCAG:T	acceptor_gain	1.0000
17:28917447:CAG:C	acceptor_gain	1.0000
17:28917447:CAGC:C	acceptor_gain	1.0000
17:28917448:AG:A	acceptor_gain	1.0000
17:28917449:GC:G	acceptor_loss	1.0000
17:28917450:C:CC	acceptor_gain	1.0000
17:28917457:C:CT	acceptor_gain	1.0000
17:28921683:AATAC:A	donor_loss	1.0000
17:28921684:ATAC:A	donor_loss	1.0000
17:28921685:TAC:T	donor_loss	1.0000
17:28921686:A:AG	donor_loss	1.0000
17:28921687:C:A	donor_loss	1.0000
17:28921687:CCTG:C	donor_gain	1.0000
17:28921809:C:CA	acceptor_loss	1.0000
17:28923904:CTGA:C	donor_loss	1.0000
17:28923906:GAC:G	donor_loss	1.0000
17:28923907:A:C	donor_loss	1.0000
17:28923908:C:A	donor_loss	1.0000
17:28927061:TTA:T	acceptor_gain	1.0000

AlphaMissense

6575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28906345:G:C	S951R	1.000
17:28906345:G:T	S951R	1.000
17:28906347:T:G	S951R	1.000
17:28906358:A:G	L947P	1.000
17:28906364:G:T	A945D	1.000
17:28906370:C:T	G943D	1.000
17:28906371:C:A	G943C	1.000
17:28906371:C:G	G943R	1.000
17:28906373:T:A	E942V	1.000
17:28906375:C:A	W941C	1.000
17:28906375:C:G	W941C	1.000
17:28906376:C:G	W941S	1.000
17:28906377:A:G	W941R	1.000
17:28906377:A:T	W941R	1.000
17:28906379:C:T	G940D	1.000
17:28906931:A:C	Y869D	1.000
17:28906942:T:A	D865V	1.000
17:28906943:C:G	D865H	1.000
17:28906954:C:A	G861V	1.000
17:28906954:C:T	G861E	1.000
17:28906955:C:A	G861W	1.000
17:28906955:C:G	G861R	1.000
17:28906955:C:T	G861R	1.000
17:28906962:A:C	S858R	1.000
17:28906962:A:T	S858R	1.000
17:28906963:C:A	S858I	1.000
17:28906964:T:G	S858R	1.000
17:28906968:G:C	N856K	1.000
17:28906968:G:T	N856K	1.000
17:28906975:A:G	L854P	1.000

dbSNP variants (sampled 300 via entrez): RS1000045083 (17:28913590 C>T), RS1000294506 (17:28939632 T>C,G), RS1000336892 (17:28946133 GAAAAAC>G,GAAAAACAAAAAC), RS1000426230 (17:28945517 G>A), RS1000443880 (17:28951462 C>A,T), RS1000523708 (17:28919036 G>A), RS1000741650 (17:28911505 A>C,G), RS1000818937 (17:28950520 T>C), RS1000852620 (17:28905833 A>T), RS1000925538 (17:28932216 T>C), RS1001040676 (17:28912171 C>T), RS1001057743 (17:28918203 T>C), RS1001156190 (17:28911880 G>A,C), RS1001230108 (17:28940519 C>T), RS1001262377 (17:28945869 C>G)

Disease associations

OMIM: gene MIM:618645 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

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

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Ozone	affects expression, increases abundance	1
Dronabinol	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Gold Compounds	decreases methylation, increases expression	1
Cadmium Chloride	increases abundance, decreases expression	1
Particulate Matter	increases abundance, increases expression	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