PNKP

Summary

PNKP (polynucleotide kinase 3’-phosphatase, HGNC:9154) is a protein-coding gene on chromosome 19q13.33, encoding Bifunctional polynucleotide phosphatase/kinase (Q96T60). Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. It is a selective cancer dependency (DepMap: 46.8% of cell lines).

This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5’ phosphorylation and 3’ dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.

Source: NCBI Gene 11284 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly, seizures, and developmental delay (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 1,274 total — 75 pathogenic, 54 likely-pathogenic
• Phenotypes (HPO): 108
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 46.8% of screened cell lines
• MANE Select transcript: NM_007254

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9154
Approved symbol	PNKP
Name	polynucleotide kinase 3’-phosphatase
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	PNK
Ensembl gene	ENSG00000039650
Ensembl biotype	protein_coding
OMIM	605610
Entrez	11284

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 28 protein_coding, 10 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 non_stop_decay

ENST00000322344, ENST00000593706, ENST00000593946, ENST00000594661, ENST00000595081, ENST00000595792, ENST00000596014, ENST00000596624, ENST00000596726, ENST00000597965, ENST00000598020, ENST00000599454, ENST00000599543, ENST00000600573, ENST00000600910, ENST00000601816, ENST00000625216, ENST00000625299, ENST00000626274, ENST00000627232, ENST00000627317, ENST00000629088, ENST00000629179, ENST00000631020, ENST00000636214, ENST00000636840, ENST00000636994, ENST00000637325, ENST00000637897, ENST00000638016, ENST00000640501, ENST00000861311, ENST00000861312, ENST00000861313, ENST00000934444, ENST00000934445, ENST00000934446, ENST00000934447, ENST00000934448, ENST00000934449, ENST00000934450, ENST00000934451, ENST00000934452, ENST00000965094, ENST00000965095, ENST00000965096

RefSeq mRNA: 1 — MANE Select: NM_007254 NM_007254

CCDS: CCDS12783

Canonical transcript exons

ENST00000322344 — 17 exons

Exon	Start	End
ENSE00003088126	49867469	49867576
ENSE00003482998	49861449	49861510
ENSE00003487512	49864179	49864236
ENSE00003498896	49863964	49864071
ENSE00003523387	49862690	49862738
ENSE00003528547	49862044	49862105
ENSE00003538619	49861204	49861365
ENSE00003556723	49863689	49863760
ENSE00003558663	49865127	49865426
ENSE00003578285	49862371	49862463
ENSE00003587695	49862185	49862281
ENSE00003600378	49862538	49862608
ENSE00003601109	49866399	49866445
ENSE00003629452	49864324	49864403
ENSE00003661218	49867054	49867217
ENSE00003674200	49861772	49861881
ENSE00003676144	49861608	49861695

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2600 / max 220.0089, expressed in 1809 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182090	10.0968	1789
182089	4.9498	1691
182088	3.6555	1525
182087	0.8093	437
182106	0.7486	410
182107	0.3939	199

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.99	gold quality
granulocyte	CL:0000094	97.97	gold quality
right adrenal gland cortex	UBERON:0035827	97.96	gold quality
right adrenal gland	UBERON:0001233	97.95	gold quality
adenohypophysis	UBERON:0002196	97.66	gold quality
right lobe of thyroid gland	UBERON:0001119	97.60	gold quality
metanephros cortex	UBERON:0010533	97.53	gold quality
left adrenal gland	UBERON:0001234	97.52	gold quality
left adrenal gland cortex	UBERON:0035825	97.48	gold quality
left lobe of thyroid gland	UBERON:0001120	97.11	gold quality
adrenal cortex	UBERON:0001235	96.71	gold quality
pituitary gland	UBERON:0000007	96.66	gold quality
right ovary	UBERON:0002118	96.49	gold quality
apex of heart	UBERON:0002098	96.45	gold quality
adrenal gland	UBERON:0002369	96.45	gold quality
left uterine tube	UBERON:0001303	96.38	gold quality
left ovary	UBERON:0002119	96.34	gold quality
sural nerve	UBERON:0015488	96.06	gold quality
body of uterus	UBERON:0009853	96.03	gold quality
thyroid gland	UBERON:0002046	95.92	gold quality
body of stomach	UBERON:0001161	95.88	gold quality
spleen	UBERON:0002106	95.82	gold quality
endocervix	UBERON:0000458	95.79	gold quality
body of pancreas	UBERON:0001150	95.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.59	gold quality
transverse colon	UBERON:0001157	95.54	gold quality
ectocervix	UBERON:0012249	95.43	gold quality
tibial nerve	UBERON:0001323	95.28	gold quality
minor salivary gland	UBERON:0001830	95.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.67

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 46.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining (PMID:12032095)
• First direct physical evidence for ternary complex formation involving a polynucleotide kinase, AMP-PNP, and an oligonucleotide, supports a reaction mechanism in which ATP and DNA bind simultaneously to the enzyme. (PMID:14556639)
• Data show that polynucleotide kinase is associated with the PARP-1-dependent end-joining pathway, and show functional parallels between the PARP-1 and DNA-PK-dependent end-joining processes. (PMID:16364363)
• polynucleotide kinase participates in repair of DNA double-strand breaks by nonhomologous end joining but not homologous recombination (PMID:17638872)
• XRCC1 enhances the capacity of hPNK to discriminate between strand breaks with 5’-OH termini and those with 5’-phosphate termini; and XRCC1 stimulates hPNK activity by displacing hPNK from the phosphorylated DNA product (PMID:17650498)
• The PNKP T5644G variant does not seem to be involved in adenoma recurrence in the Polyp Prevention Trial. (PMID:18414202)
• the FHA domain of PNK binds specifically, and with high affinity to a multiply phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1 PNK:XRCC1 complex. (PMID:19155274)
• The neurological abnormalities in individuals with microcephaly, early onset, intractable seizures and develomental delays may reflect a role for PNKP in several DNA repair pathways. (PMID:20118933)
• CK2-mediated phosphorylation of XRCC4 can have different effects on PNKP activity. (PMID:20852255)
• Studies indicate that PNKP serves a crucial role in the repair of DNA strand breaks through interactions with other DNA repair proteins, notably XRCC1 and XRCC4. (PMID:21353781)
• Results reveal that ionizing radiation-induced phosphorylation of PNKP by ATM and DNA-PK regulates PNKP function at DNA double strand breaks. (PMID:21824916)
• the critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome. (PMID:22130663)
• PNKP distorts target DNA structures to access damaged substrate DNA ends, thus providing a molecular mechanism for the involvement of PNKP in the repair of both single- and double-strand breaks. (PMID:22171004)
• The data suggest that all four known mutations associated with microcephaly, seizures and developmental delay reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5’-kinase activity and all of the mutations greatly reducing cellular DNA 3’-phosphatase activity. (PMID:22508754)
• the interaction between PNKP and XRCC1 has roles in the retention of XRCC1 at DNA damage sites and in DNA alkylation damage repair (PMID:22992732)
• Mutations in PNKP have previously been associated with a syndrome of microcephaly, seizures and developmental delay (MIM 613402), and is now associated with a neurodegenerative disorder. (PMID:23224214)
• we show that modest inhibition of PNKP in a PTEN knockout background enhances cellular radiosensitivity, suggesting that such a “synthetic sickness” approach involving the combination of PNKP inhibition with radiotherapy (PMID:23883586)
• We now report that the mutant ATXN3 protein interacts with and inactivates PNKP (polynucleotide kinase 3’-phosphatase), an essential DNA strand break repair enzyme (PMID:25590633)
• Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP’s 3’ phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity (PMID:25633985)
• We identified homozygous or compound-heterozygous PNKP mutations in eight of the nine Portuguese families we studied, suggesting that, in Portugal, mutations in PNKP are the most frequent cause of ataxia with oculomotor apraxia. (PMID:25728773)
• In 11 Portuguese patients, PNKP mutations cause ataxia with oculomotor apraxia type 4. (PMID:26970421)
• the role for PNKP in maintaining brain function and how perturbation in its activity can account for the varied pathology of neurodegeneration or microcephaly present in microcephaly with seizures and ataxia with oculomotor apraxia 4 respectively. (PMID:27125728)
• we have identified a mutation in PNKP, leading to a phenotype of microcephaly with primordial dwarfism. (PMID:27232581)
• Mutations in TDP1 and APTX have been linked to Spinocerebellar ataxia with axonal neuropathy (SCAN1) and Ataxia-ocular motor apraxia 1 (AOA1), respectively, while mutations in PNKP are considered to be responsible for Microcephaly with seizures (MCSZ) and Ataxia-ocular motor apraxia 4 (AOA4). (PMID:27470939)
• In a recombinant PNKP-XRCC4-LigIV complex, stable binding of PNKP requires XRCC4 phosphorylation. Only one PNKP protomer binds per XRCC4 dimer. Both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. A surface on the PNKP phosphatase domain may contact XRCC4-LigIV. A mutation on this surface (E326K) impairs PNKP recruitment to damaged DNA and causes microcephaly with seizures. (PMID:28453785)
• PNKP mutation in two siblings is associated with progressive ataxia, abnormal saccades, sensorimotor neuropathy and dystonia consistent with ataxia with oculomotor apraxia disorders. (PMID:28552035)
• XRCC1 and PNKP interact via a high-affinity phosphorylation-dependent interaction site in XRCC1 and a forkhead-associated domain in PNKP. Data suggest a second PNKP interaction site in XRCC1 that binds PNKP with lower affinity and independently of XRCC1 phosphorylation. (XRCC1 = X-ray repair cross complementing protein 1; PNKP = polynucleotide kinase 3’-phosphatase) (PMID:28821613)
• Our results may hence improve the understanding of the mechanisms associated with DNA repair and fetaldevelopment in PNKP-associated disorders. (PMID:29243230)
• Despite presence of an alternative 3’-phosphatase, loss of PNKP significantly sensitizes cells to 3’-phosphate-terminated DSBs, due to a 3’-dephosphorylation defect. (PMID:29807321)
• PKNP variants are the major causative variant for the Charcot-Marie-Tooth disease CMT2 phenotype in these individuals and that the milder clinical manifestation is due to an allelic effect. (PMID:30039206)
• Study reports a novel missense variant c.1133A>C (p.Lys378Thr) on the 13th exon of PNKP gene identified by whole exome sequencing in an Iranian multi-affected family with microcephaly, seizures and developmental delay disorder. (PMID:30195441)
• This study found that an XRCC1 fragment, comprising residues 166-436, binds tightly to PNKP and DNA and efficiently activates PNKP’s kinase activity. (PMID:30446622)
• The authors report that HTT forms a transcription-coupled DNA repair (TCR) complex with RNA polymerase II subunit A (POLR2A), ataxin-3, the DNA repair enzyme polynucleotide-kinase-3’-phosphatase (PNKP), and cyclic AMP-response element-binding (CREB) protein (CBP). This complex senses and facilitates DNA damage repair during transcriptional elongation, but its functional integrity is impaired by mutant HTT. (PMID:30994454)
• Study provides evidence that wild-type ATXN3 plays an important role in error-free repair of DNA double-strand breaks in the transcribed genes. In contrast, mutant ATXN3 blocks the activity of a DNA end-processing enzyme, polynucleotide kinase 3’-phosphatase (PNKP), leading to progressive accumulation of double-strand breaks and abrogation of global transcription. (PMID:32205441)
• Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair. (PMID:32504494)
• The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort. (PMID:32980744)
• The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability. (PMID:33220551)
• Mutational survivorship bias: The case of PNKP. (PMID:33332469)
• PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease. (PMID:33468657)
• Characteristics of epilepsy secondary to mutations in the PNKP gene. (PMID:34247972)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pnkp	ENSDARG00000100455
mus_musculus	Pnkp	ENSMUSG00000002963
rattus_norvegicus	Pnkp	ENSRNOG00000020318
drosophila_melanogaster	PNKP	FBGN0037578
caenorhabditis_elegans		WBGENE00009010

Protein

Protein identifiers

Bifunctional polynucleotide phosphatase/kinase — Q96T60 (reviewed: Q96T60)

Alternative names: DNA 5’-kinase/3’-phosphatase, Polynucleotide kinase-3’-phosphatase

All UniProt accessions (16): A0A0D9SEV0, A0A0D9SFD6, A0A0D9SFL2, A0A0D9SFU1, Q96T60, A0A1B0GU66, A0A1B0GVJ3, A0A1B0GW17, A0A1B0GW61, A0A1W2PP58, M0QX49, M0QYH2, M0QYI1, M0R000, M0R097, M0R3C8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNK ensures that DNA termini are compatible with extension and ligation by either removing 3’-phosphates from, or by phosphorylating 5’-hydroxyl groups on, the ribose sugar of the DNA backbone.

Subunit / interactions. Monomer. Interacts (via FHA domain) with XRCC4; mainly interacts with XRCC4 phosphorylated by CK2 but is also able to interact at much lower level with unphosphorylated PNKP.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in many tissues with highest expression in spleen and testis, and lowest expression in small intestine. Expressed in higher amount in pancreas, heart and kidney and at lower levels in brain, lung and liver.

Disease relevance. Microcephaly, seizures, and developmental delay (MCSZ) [MIM:613402] An autosomal recessive neurodevelopmental disorder characterized by infantile-onset seizures, microcephaly, severe intellectual disability and delayed motor milestones with absent speech or only achieving a few words. Most patients also have behavioral problems with hyperactivity. Microcephaly is progressive and without neuronal migration or structural abnormalities, consistent with primary microcephaly. The disease is caused by variants affecting the gene represented in this entry. Ataxia-oculomotor apraxia 4 (AOA4) [MIM:616267] An autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The FHA domain binds threonine-phosphorylated peptides from XRCC1/4, and is responsible for the recruitment of PNKP to the sites of DNA repair. The affinity is ten times greater if peptides are also phosphorylated on the serine preceeding the phosphothreonine.

Similarity. In the N-terminal section; belongs to the DNA 3’ phosphatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96T60-1	1	yes
Q96T60-2	2

RefSeq proteins (1): NP_009185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006549	HAD-SF_hydro_IIIA	Domain
IPR006550	PNKP	Family
IPR006551	Polynucleotide_phosphatase	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR013954	PNK3P	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR041388	FHA_2	Domain

Pfam: PF08645, PF13671, PF17913

Enzyme classification (BRENDA):

• EC 2.7.1.78 — polynucleotide 5’-hydroxyl-kinase (BRENDA: 23 organisms, 178 substrates, 91 inhibitors, 53 Km, 17 kcat entries)
• EC 3.1.3.32 — polynucleotide 3’-phosphatase (BRENDA: 16 organisms, 42 substrates, 17 inhibitors, 55 Km, 72 kcat entries)

Substrate kinetics (BRENDA)

33 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BIS-P-NITROPHENYL PHOSPHATE	1.6–88	22
ATP	0.0007–3.4	19
2’,3’-CAMP	3.9–100	18
P-NITROPHENYL PHOSPHATE	1–75	8
5’-OH-DNA	0.0027–0.046	7
5’-HYDROXYL POLY(A)	0.0025–0.0036	2
ADP	0.2	2
MG2+	0.5–2.5	2
R(A20)	0.0013–0.0015	2
[GAMMA-S]ATP	0.22–3.1	2
5’-DEPHOSPHO-GAAAA-RNA	0.099	1
5’-DEPHOSPHO-GC-RNA	0.109	1
5’-HO-CCGACCAACGAAGGT	0.0028	1
5’-HYDROXYL POLY(C)	0.0034	1
5’-OH DNA	0.016	1

Catalyzed reactions (Rhea), 2 shown:

• a 3’end (2’-deoxyribonucleotide 3’-phosphate)-DNA + H2O = a 3’-end 2’-deoxyribonucleotide-DNA + phosphate (RHEA:14113)
• a 5’-end dephospho-2’-deoxyribonucleoside-DNA + ATP = a 5’-end 5’-phospho-2’-deoxyribonucleoside-DNA + ADP + H(+) (RHEA:15669)

UniProt features (35 total): sequence variant 10, strand 8, modified residue 4, region of interest 3, sequence conflict 3, turn 2, chain 1, domain 1, splice variant 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2BRF	X-RAY DIFFRACTION	1.4
2W3O	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96T60-F1	91.06	0.83

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 (1): 372–379

Post-translational modifications (4): 122, 1, 114, 118

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5649702	APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway

MSigDB gene sets: 377 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, GOMF_ENDONUCLEASE_ACTIVITY, WWTAAGGC_UNKNOWN, GOMF_NUCLEASE_ACTIVITY, AREB6_03, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, KAUFFMANN_DNA_REPAIR_GENES, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_DNA_REPAIR, SHIRAISHI_PLZF_TARGETS_UP, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, GOBP_NUCLEOTIDE_EXCISION_REPAIR, SRF_C

GO Biological Process (10): DNA-templated DNA replication (GO:0006261), DNA repair (GO:0006281), base-excision repair, gap-filling (GO:0006287), nucleotide-excision repair (GO:0006289), double-strand break repair via nonhomologous end joining (GO:0006303), response to oxidative stress (GO:0006979), response to radiation (GO:0009314), positive regulation of telomere maintenance (GO:0032206), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), DNA damage response (GO:0006974)

GO Molecular Function (14): damaged DNA binding (GO:0003684), double-stranded DNA binding (GO:0003690), endonuclease activity (GO:0004519), ATP binding (GO:0005524), purine nucleotide binding (GO:0017076), polynucleotide 3’-phosphatase activity (GO:0046403), ATP-dependent polydeoxyribonucleotide 5’-hydroxyl-kinase activity (GO:0046404), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), hydrolase activity (GO:0016787), ATP-dependent polynucleotide 5’-hydroxyl-kinase activity (GO:0051734)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), membrane (GO:0016020), site of double-strand break (GO:0035861), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Resolution of Abasic Sites (AP sites)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
DNA binding	2
catalytic activity	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
DNA replication	1
DNA damage response	1
base-excision repair	1
DNA repair	1
double-strand break repair	1
response to stress	1
response to abiotic stimulus	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
double-strand break repair via nonhomologous end joining	1
positive regulation of double-strand break repair	1
regulation of double-strand break repair via nonhomologous end joining	1
cellular response to stress	1
nuclease activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleotide binding	1
phosphatase activity	1
ATP-dependent polynucleotide 5’-hydroxyl-kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
polynucleotide 5’-hydroxyl-kinase activity	1
intracellular membrane-bounded organelle	1
site of DNA damage	1

Protein interactions and networks

STRING

2026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNKP	XRCC1	P18887	998
PNKP	LIG3	P49916	980
PNKP	XRCC4	Q13426	971
PNKP	TDP1	Q9NUW8	920
PNKP	APEX1	P27695	916
PNKP	POLB	P06746	903
PNKP	APLF	Q8IW19	868
PNKP	OGG1	P78554	838
PNKP	PAXX	Q9BUH6	835
PNKP	NEIL1	Q96FI4	809
PNKP	SLC25A22	Q9H936	797
PNKP	PCDH19	Q8TAB3	796
PNKP	XRCC6	P12956	784
PNKP	WRN	Q14191	781
PNKP	NEIL2	Q969S2	777

IntAct

225 interactions, top by confidence:

A	B	Type	Score
XRCC4	PNKP	psi-mi:“MI:0915”(physical association)	0.950
PNKP	XRCC4	psi-mi:“MI:2364”(proximity)	0.950
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
TRIM37	PNKP	psi-mi:“MI:0915”(physical association)	0.740
TRIM37	PNKP	psi-mi:“MI:2364”(proximity)	0.740
LIG3	XRCC1	psi-mi:“MI:0914”(association)	0.740
ZBTB14	PNKP	psi-mi:“MI:0915”(physical association)	0.720
PNKP	TNIP1	psi-mi:“MI:0915”(physical association)	0.720
ZNF639	PNKP	psi-mi:“MI:0915”(physical association)	0.720
PNKP	ZBTB14	psi-mi:“MI:0915”(physical association)	0.720
PNKP	ZNF639	psi-mi:“MI:0915”(physical association)	0.720
TNIP1	PNKP	psi-mi:“MI:0915”(physical association)	0.720
CCDC43	PNKP	psi-mi:“MI:0914”(association)	0.640
PNKP	IKZF1	psi-mi:“MI:0915”(physical association)	0.560
IKZF1	PNKP	psi-mi:“MI:0915”(physical association)	0.560
DVL3	PNKP	psi-mi:“MI:0915”(physical association)	0.560
KANK2	PNKP	psi-mi:“MI:0915”(physical association)	0.560
PNKP	CARD10	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	PNKP	psi-mi:“MI:0915”(physical association)	0.560
PNKP	PICK1	psi-mi:“MI:0915”(physical association)	0.560
PNKP	THAP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (194): PNKP (Two-hybrid), PNKP (Two-hybrid), PNKP (Two-hybrid), ZNF639 (Two-hybrid), PNKP (Affinity Capture-MS), PNKP (Affinity Capture-MS), PNKP (Affinity Capture-MS), PNKP (Affinity Capture-MS), KRTAP4-12 (Two-hybrid), MYOZ1 (Two-hybrid), PNKP (Two-hybrid), PNKP (Two-hybrid), DCPS (Co-fractionation), SBDS (Co-fractionation), PNKP (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A2BDX3, A4RPM5, A5GFZ6, A6NK58, B4FAT0, B4NXF7, B6TNK6, O19179, O43323, O95396, O95571, P19971, P55203, P85971, Q02846, Q05922, Q08DH8, Q0VFH3, Q14BV6, Q17CA7, Q1WNP0, Q3KQV9, Q3TW96, Q3UQ84, Q561R2, Q58E95, Q5PQQ1, Q5ZKI2, Q61488, Q66JK4, Q6PAT0, Q7PY41, Q86U10, Q8AWD2, Q8NFV4, Q8VBZ0, Q8VDG5, Q923K4, Q96EY9

Diamond homologs: A6TBC5, O13911, P21286, Q03796, Q19683, Q5UQD2, Q7MLS4, Q7VQW8, Q84JE8, Q87QK9, Q8D8Q2, Q96T60, Q9JLV6, Q9M041, P61797, P61798, P61799, P61800, P61801, P61802, Q558W0, Q7T287, Q7TQC5, Q7YRZ1, Q7YRZ2, Q7Z2E3, Q8K3P7, Q8K4H4, Q8MSG8, Q9BGQ0, Q9CPS6, Q08702, Q28BZ2, Q5R9L4, Q9NQE9, O84390, P62958, Q5RF69, Q84VV6, Q9PK09

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	PNKP	phosphorylation
PRKDC	up-regulates	PNKP	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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.

GO biological processes:

GO term	Partners	Fold	FDR
base-excision repair	5	27.2×	7e-04
double-strand break repair	6	14.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1274 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	54
Uncertain significance	478
Likely benign	497
Benign	27

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1033198	NM_007254.4(PNKP):c.1227_1228del (p.Cys409_Glu410delinsTer)	Pathogenic
1069274	NM_007254.4(PNKP):c.984del (p.Leu329fs)	Pathogenic
1071624	NM_007254.4(PNKP):c.318G>A (p.Trp106Ter)	Pathogenic
1071794	NM_007254.4(PNKP):c.1059C>A (p.Cys353Ter)	Pathogenic
1074930	NC_000019.9:g.(?50364485)(50370481_?)del	Pathogenic
1075417	NM_007254.4(PNKP):c.1299-2A>G	Pathogenic
1300178	NM_007254.4(PNKP):c.1299-5_1303del	Pathogenic
1371267	NM_007254.4(PNKP):c.1311T>A (p.Cys437Ter)	Pathogenic
1412103	NM_007254.4(PNKP):c.1390C>T (p.Arg464Ter)	Pathogenic
1419965	NM_007254.4(PNKP):c.808C>T (p.Gln270Ter)	Pathogenic
1452109	NM_007254.4(PNKP):c.1448+2T>A	Pathogenic
1452440	NM_007254.4(PNKP):c.1543dup (p.Tyr515fs)	Pathogenic
1453217	NM_007254.4(PNKP):c.756_760del (p.Thr253fs)	Pathogenic
1455443	NM_007254.4(PNKP):c.1270_1283dup (p.Ala429fs)	Pathogenic
1460226	NM_007254.4(PNKP):c.847del (p.Asp283fs)	Pathogenic
1806352	NM_007254.4(PNKP):c.1286_1287insTAAGC (p.Ser430fs)	Pathogenic
187766	NM_007254.4(PNKP):c.1123G>T (p.Gly375Trp)	Pathogenic
187767	NM_007254.4(PNKP):c.1322_1323insAGCCG (p.Gly442fs)	Pathogenic
187768	NM_007254.4(PNKP):c.1549_1550insTGTACTGC (p.Gln517fs)	Pathogenic
1951839	NM_007254.4(PNKP):c.113del (p.Leu38fs)	Pathogenic
1955429	NM_007254.4(PNKP):c.298dup (p.His100fs)	Pathogenic
1993622	NM_007254.4(PNKP):c.999_1005dup (p.Phe336fs)	Pathogenic
2028325	NM_007254.4(PNKP):c.1481_1500dup (p.Ile501fs)	Pathogenic
206387	NM_007254.4(PNKP):c.490C>T (p.Gln164Ter)	Pathogenic
206398	NM_007254.4(PNKP):c.992G>A (p.Trp331Ter)	Pathogenic
206406	NM_007254.4(PNKP):c.1189-2A>C	Pathogenic
206426	NM_007254.4(PNKP):c.1288_1294dup (p.Ala432fs)	Pathogenic
206427	NM_007254.4(PNKP):c.1293_1298+2dup	Pathogenic
2083812	NM_007254.4(PNKP):c.1333del (p.Cys445fs)	Pathogenic
2086105	NM_007254.4(PNKP):c.394_395del (p.Asp132fs)	Pathogenic

SpliceAI

3664 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49861511:C:CC	acceptor_gain	1.0000
19:49861602:GCTCA:G	donor_loss	1.0000
19:49861603:CTCAC:C	donor_loss	1.0000
19:49861604:TCA:T	donor_loss	1.0000
19:49861605:CACCC:C	donor_loss	1.0000
19:49861606:AC:A	donor_gain	1.0000
19:49861607:CC:C	donor_gain	1.0000
19:49861691:CGTAC:C	acceptor_gain	1.0000
19:49861692:GTAC:G	acceptor_gain	1.0000
19:49861693:TAC:T	acceptor_gain	1.0000
19:49861694:AC:A	acceptor_gain	1.0000
19:49861695:CC:C	acceptor_gain	1.0000
19:49861696:CTGTG:C	acceptor_loss	1.0000
19:49861767:GCTA:G	donor_loss	1.0000
19:49861768:CTA:C	donor_loss	1.0000
19:49861769:TACCT:T	donor_loss	1.0000
19:49861770:A:AT	donor_loss	1.0000
19:49861771:CCTG:C	donor_loss	1.0000
19:49861877:GTGTC:G	acceptor_gain	1.0000
19:49861878:TGTC:T	acceptor_gain	1.0000
19:49861879:GTC:G	acceptor_gain	1.0000
19:49861880:TC:T	acceptor_gain	1.0000
19:49861881:CC:C	acceptor_gain	1.0000
19:49861882:C:CC	acceptor_gain	1.0000
19:49863686:CA:C	donor_loss	1.0000
19:49863687:A:AC	donor_gain	1.0000
19:49863687:AC:A	donor_gain	1.0000
19:49863687:ACCTG:A	donor_gain	1.0000
19:49863688:C:CT	donor_gain	1.0000
19:49863688:CC:C	donor_gain	1.0000

AlphaMissense

3342 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49862196:C:T	G372E	0.994
19:49862205:A:T	V369D	0.992
19:49862597:G:T	R293S	0.992
19:49861779:G:T	R431S	0.991
19:49862556:G:C	F306L	0.991
19:49862556:G:T	F306L	0.991
19:49862558:A:G	F306L	0.991
19:49861653:G:C	C447W	0.990
19:49861330:A:G	F495S	0.989
19:49861795:G:C	N425K	0.989
19:49861795:G:T	N425K	0.989
19:49862098:C:A	K378N	0.989
19:49862098:C:G	K378N	0.989
19:49862197:C:G	G372R	0.989
19:49862197:C:T	G372R	0.989
19:49862096:G:A	S379F	0.988
19:49864058:G:A	T217I	0.988
19:49864347:A:C	F185L	0.988
19:49864347:A:T	F185L	0.988
19:49864349:A:G	F185L	0.988
19:49861655:A:G	C447R	0.987
19:49862208:A:T	V368D	0.987
19:49864328:A:G	W192R	0.987
19:49864328:A:T	W192R	0.987
19:49862097:A:G	S379P	0.986
19:49862437:G:C	F321L	0.986
19:49862437:G:T	F321L	0.986
19:49862439:A:G	F321L	0.986
19:49862459:G:T	A314D	0.986
19:49861806:C:G	D422H	0.985

dbSNP variants (sampled 300 via entrez): RS1000389864 (19:49862317 C>G,T), RS1000619906 (19:49866267 T>C), RS1000818731 (19:49866043 C>T), RS1001216105 (19:49862352 C>T), RS1001338139 (19:49861703 G>A), RS1001992908 (19:49868523 G>A,T), RS1002399157 (19:49860990 C>T), RS1002874029 (19:49869225 T>A,C), RS1002955115 (19:49866875 A>C), RS1002964945 (19:49867704 G>A,C), RS1003240282 (19:49863206 TC>T), RS1003952243 (19:49868249 C>CGCCCACCTCG), RS1003966736 (19:49866710 G>A), RS1004562051 (19:49862158 G>A,T), RS1004621657 (19:49866388 G>A,C)

Disease associations

OMIM: gene MIM:605610 | disease phenotypes: MIM:613722, MIM:616267, MIM:613402, MIM:605589, MIM:208920

GenCC curated gene-disease

Disease	Classification	Inheritance
ataxia - oculomotor apraxia type 4	Definitive	Autosomal recessive
microcephaly, seizures, and developmental delay	Strong	Autosomal recessive
Charcot-Marie-Tooth disease type 2B2	Strong	Autosomal recessive
genetic developmental and epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
microcephaly, seizures, and developmental delay	Definitive	AR

Mondo (10): developmental and epileptic encephalopathy, 12 (MONDO:0013389), ataxia - oculomotor apraxia type 4 (MONDO:0014557), microcephaly, seizures, and developmental delay (MONDO:0013254), Charcot-Marie-Tooth disease type 2B2 (MONDO:0011570), ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (MONDO:0008842), microcephaly (MONDO:0001149), congenital nervous system disorder (MONDO:0002320), intellectual disability (MONDO:0001071), pyridoxine-dependent epilepsy (MONDO:0009945), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (7): Ataxia-oculomotor apraxia type 4 (Orphanet:459033), Early infantile developmental and epileptic encephalopathy (Orphanet:1934), Charcot-Marie-Tooth disease type 2B2 (Orphanet:101101), Ataxia-oculomotor apraxia type 1 (Orphanet:1168), Pyridoxine-dependent-developmental and epileptic encephalopathy (Orphanet:3006), OBSOLETE: Microcephaly-seizures-developmental delay syndrome (Orphanet:228418), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

108 total (30 of 108 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000340	Sloping forehead
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000570	Abnormal saccadic eye movements
HP:0000657	Oculomotor apraxia
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000752	Hyperactivity
HP:0000826	Precocious puberty
HP:0001009	Telangiectasia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001266	Choreoathetosis
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537991	Charcot-Marie-Tooth disease, Type 2B2 (supp.)
C538013	Early-onset ataxia with oculomotor apraxia and hypoalbuminemia (supp.)
C536254	Pyridoxine-dependent epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523434 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(7aS)-2-[(1S)-1-hydroxyundecyl]-6-[2-(1H-indol-3-yl)ethyl]-1-(4-nitroanilino)-4a,7a-dihydro-2H-pyrrolo[3,4-b]pyridine-5,7-dione	KD	260 nM	US-11325905: Imidopiperidine compounds as inhibitors of human polynucleotide kinase phosphatase

ChEMBL bioactivities

86 potent at pChembl≥5 of 105 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	IC50	60	nM	CHEMBL4303462
7.10	Kd	80	nM	CHEMBL5940507
7.07	Kd	85	nM	CHEMBL5929988
7.05	Kd	90	nM	CHEMBL5939213
7.02	Kd	95	nM	CHEMBL5909837
7.00	Kd	100	nM	CHEMBL5805253
6.98	Kd	105	nM	CHEMBL6056932
6.98	Kd	105	nM	CHEMBL5783010
6.92	Kd	120	nM	CHEMBL5962752
6.92	Kd	120	nM	CHEMBL5985889
6.92	Kd	120	nM	CHEMBL5816775
6.89	Kd	130	nM	CHEMBL5832052
6.87	Kd	135	nM	CHEMBL6025566
6.87	Kd	135	nM	CHEMBL5903908
6.87	Kd	135	nM	CHEMBL5948900
6.85	Kd	140	nM	CHEMBL5998908
6.85	Kd	140	nM	CHEMBL5839762
6.85	Kd	140	nM	CHEMBL6027119
6.85	Kd	140	nM	CHEMBL5900144
6.85	Kd	140	nM	CHEMBL5940201
6.85	Kd	140	nM	CHEMBL5942471
6.84	Kd	145	nM	CHEMBL6030874
6.82	Kd	150	nM	CHEMBL6055591
6.82	Kd	150	nM	CHEMBL5813053
6.82	Kd	150	nM	CHEMBL6022485
6.81	Kd	155	nM	CHEMBL5966528
6.80	Kd	160	nM	CHEMBL5854053
6.80	Kd	160	nM	CHEMBL5803720
6.80	Kd	160	nM	CHEMBL6040741
6.80	Kd	160	nM	CHEMBL6003890
6.80	Kd	160	nM	CHEMBL5922626
6.80	Kd	160	nM	CHEMBL5931429
6.77	Kd	170	nM	CHEMBL5848244
6.77	Kd	170	nM	CHEMBL5953773
6.75	Kd	180	nM	CHEMBL5832107
6.75	Kd	180	nM	CHEMBL6062386
6.72	Kd	190	nM	CHEMBL5840782
6.72	Kd	190	nM	CHEMBL5760877
6.70	Kd	200	nM	CHEMBL5950724
6.70	Kd	200	nM	CHEMBL6001377
6.70	Kd	200	nM	CHEMBL6062844
6.70	Kd	200	nM	CHEMBL5830638
6.66	Kd	220	nM	CHEMBL5849185
6.66	Kd	220	nM	CHEMBL6014022
6.64	Kd	230	nM	CHEMBL5954052
6.64	Kd	230	nM	CHEMBL5787057
6.62	Kd	240	nM	CHEMBL6016428
6.62	Kd	240	nM	CHEMBL5979527
6.62	Kd	240	nM	CHEMBL6021649
6.60	Kd	250	nM	CHEMBL6007018

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Cyclosporine	increases expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	increases expression	1
potassium bromate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
fludarabine	affects cotreatment, decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
cerous chloride	decreases expression	1
aflatoxin B2	decreases methylation, increases methylation	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
CPG-oligonucleotide	decreases expression	1
LAQ824	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419640	Binding	Inhibition of recombinant human PNKP assessed as reduction in PNKP 3’-phosphatase activity by measuring release of inorganic phosphate using 5’-TAMRA-tagged 20-mer oligonucleotide as substrate incubated for 30 mins by fluorescence quenching	Small molecule inhibitors of polynucleotide kinase/phosphatase, poly(ADP-ribose) polymerase and uses thereof

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia