PAFAH1B1

Summary

PAFAH1B1 (platelet activating factor acetylhydrolase 1b regulatory subunit 1, HGNC:8574) is a protein-coding gene on chromosome 17p13.3, encoding Platelet-activating factor acetylhydrolase IB subunit beta (P43034). Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This locus was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker lissencephaly syndrome. This gene encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum.

Source: NCBI Gene 5048 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lissencephaly due to LIS1 mutation (Definitive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 612 total — 140 pathogenic, 56 likely-pathogenic
• Phenotypes (HPO): 84
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000430

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8574
Approved symbol	PAFAH1B1
Name	platelet activating factor acetylhydrolase 1b regulatory subunit 1
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	LIS1, PAFAH, NudF
Ensembl gene	ENSG00000007168
Ensembl biotype	protein_coding
OMIM	601545
Entrez	5048

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 30 protein_coding, 8 retained_intron, 7 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay

ENST00000397193, ENST00000397195, ENST00000570400, ENST00000571289, ENST00000571495, ENST00000572915, ENST00000574213, ENST00000574468, ENST00000574816, ENST00000575477, ENST00000576586, ENST00000609078, ENST00000610190, ENST00000674608, ENST00000674717, ENST00000675084, ENST00000675202, ENST00000675331, ENST00000675385, ENST00000675390, ENST00000675430, ENST00000675574, ENST00000675621, ENST00000675764, ENST00000676077, ENST00000676098, ENST00000676188, ENST00000676201, ENST00000676353, ENST00000676456, ENST00000713668, ENST00000713688, ENST00000713689, ENST00000713690, ENST00000713983, ENST00000713984, ENST00000713986, ENST00000713987, ENST00000863847, ENST00000863848, ENST00000863849, ENST00000863850, ENST00000863851, ENST00000863852, ENST00000863853, ENST00000863854, ENST00000934916, ENST00000934917, ENST00000934918, ENST00000934919, ENST00000971580

RefSeq mRNA: 1 — MANE Select: NM_000430 NM_000430

CCDS: CCDS32528

Canonical transcript exons

ENST00000397195 — 11 exons

Exon	Start	End
ENSE00002643887	2666992	2667198
ENSE00003269535	2665372	2665456
ENSE00003545970	2666016	2666090
ENSE00003703939	2638099	2638320
ENSE00004020626	2680164	2680320
ENSE00004020628	2670163	2670331
ENSE00004020629	2672655	2672757
ENSE00004020630	2676505	2676606
ENSE00004020632	2681729	2685615
ENSE00004020633	2674060	2674288
ENSE00004020723	2593654	2594006

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.0379 / max 760.7416, expressed in 1811 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158834	34.8762	1809
158839	8.1738	1705
158836	2.2111	1229
158840	0.8800	512
158835	0.7667	442
158838	0.0853	23
158837	0.0448	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.72	gold quality
male germ cell	CL:0000015	99.36	gold quality
middle temporal gyrus	UBERON:0002771	99.08	gold quality
left testis	UBERON:0004533	99.02	gold quality
right testis	UBERON:0004534	98.90	gold quality
cerebellar vermis	UBERON:0004720	98.90	gold quality
frontal pole	UBERON:0002795	98.89	gold quality
pons	UBERON:0000988	98.72	gold quality
paraflocculus	UBERON:0005351	98.71	gold quality
orbitofrontal cortex	UBERON:0004167	98.57	gold quality
cortical plate	UBERON:0005343	98.49	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.38	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.34	gold quality
medial globus pallidus	UBERON:0002477	98.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.22	gold quality
cerebellar cortex	UBERON:0002129	98.02	gold quality
globus pallidus	UBERON:0001875	98.01	gold quality
cerebellum	UBERON:0002037	98.01	gold quality
cerebellar hemisphere	UBERON:0002245	98.00	gold quality
superior frontal gyrus	UBERON:0002661	97.99	gold quality
superior vestibular nucleus	UBERON:0007227	97.97	gold quality
occipital lobe	UBERON:0002021	97.89	gold quality
postcentral gyrus	UBERON:0002581	97.86	gold quality
parietal lobe	UBERON:0001872	97.84	gold quality
prefrontal cortex	UBERON:0000451	97.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.81	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.79	gold quality
primary visual cortex	UBERON:0002436	97.78	gold quality
frontal cortex	UBERON:0001870	97.76	gold quality
dorsal root ganglion	UBERON:0000044	97.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.22
E-MTAB-6524	no	185.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GDNF

miRNA regulators (miRDB)

364 targeting PAFAH1B1, 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-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• LIS1 has a principle role in brain development.Hemizygote mutations result in a severe brain malformation known as lissencephaly. It is a WD repeat protein involved in several protein complexes that may play a functional role in brain development. (PMID:11803439)
• Together, our data suggest a novel role for LIS1 in mediating CLIP-170-dynein interactions and in coordinating dynein cargo-binding and motor activities. (PMID:11889140)
• Val279Phe polymorphism is activity-deficient and is associated with increased risk of childhood atopic asthma. (PMID:11916011)
• LIS1, CLIP-170’s key to the dynein/dynactin pathway (PMID:11940666)
• Lissencephaly with posteriorly predominant gyral abnormality is caused by mutations of the LIS1 gene on chromosome 17. (PMID:12185771)
• The propensity of monocytes in juvenile periodontitis patients to differentiate into monocyte-derived dendritic cells results in lower levels of PAFAH and allows platelet activating factor to promote production of a protective IgG2 antibody response. (PMID:12496397)
• LIS1 missense mutations result in variable phenotypes (PMID:12885786)
• LIS1 maps at 17p13.3 and is the result of a heterozygous mutation. It acts during corticogenesis on radial migratory pathways. (PMID:15057976)
• Our results indicate that Tat interacts with LIS1 in vitro and in vivo and that this interaction might contribute to the effect of Tat on microtubule formation. (PMID:15698475)
• V279F polymorphism in the plasma PAF-AH gene and consequent enzymatic deficiency is an important factor for IVIG nonresponse in Japanese patients with acute KD. (PMID:16027700)
• use of poliovirus protein as a research tool allowed us to reveal the role of cellular protein LIS1 in membrane protein trafficking, maintenance of Golgi integrity, surface presentation of unstable receptors (PMID:16138011)
• LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. (PMID:16144905)
• Mutations within the LisH (LIS1 homology)motif are likely to result in pathogenic consequences in genes associated with genetic diseases. (PMID:16258276)
• in addition to migration, disruption in cell proliferation could play a more important role in the development of lissencephaly than previously suspected (PMID:16642511)
• Our results show that inhibition of PP2A by LIS1 induces HIV-1 transcription. Our results also point to a possibility that LIS1 might function in the cells as a yet unrecognized regulatory subunit of PP2A. (PMID:17018134)
• Neither type nor position of intragenic mutations in the LIS1 gene allows prediction of the phenotypic severity. Patients presenting with mild cerebral malformations should be considered for genetic analysis of the LIS1 gene. (PMID:17664403)
• LIS1 has a role in lissencephaly, neuronal migration and development [review] (PMID:17850624)
• The high frequency of genomic deletions/duplications of LIS1 is in keeping with the over representation of Alu elements in the 17p13.3 region. (PMID:18285425)
• LIS1 regulates cytoplasmic dynein and plays an important role on the determination cleavage plane of neuronal progenitor cells. (PMID:18421979)
• regulates cytoplasmic dynein. [review] (PMID:18524253)
• Data show that LIS1 suppresses the motility of cytoplasmic dynein on microtubules, whereas NDEL1 releases the blocking effect of LIS1 on cytoplasmic dynein. (PMID:18784752)
• these results suggest that complexes of dynein, Lis1 and CLIP-170 crosslink and slide microtubules within the spindle, thereby producing an inward force that pulls centrosomes together. (PMID:19020519)
• intragenic deletions and duplications of the LIS1 gene account for a significant number of patients with isolated lissencephaly sequence and subcortical band heterotopia, where no molecular defect had previously been identified. (PMID:19050731)
• An increase in LIS1 expression in the developing brain results in brain abnormalities in mice and humans. (PMID:19136950)
• These results indicate an antagonistic effect of alpha1, alpha2 and Ndel1 for Lis1 binding, probably to modulate dynein functions in vivo. (PMID:19622634)
• There was no strong evidence for association with LIS1 in schizophrenia. (PMID:19632097)
• Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations. (PMID:19667223)
• NDE1 and NDEL1 act upstream of LIS1 in dynein recruitment, and/or activation, on the membrane. (PMID:20048338)
• NudCL2, a homolog of Aspergillus NudC, which shares significant homology with human NudC and NudCL was identified. It regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. (PMID:20133715)
• Findings suggest that physiological functions of LIS1 and NDEL1 in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. (PMID:20168084)
• NudC may be involved in the regulation of LIS1 stability by its chaperone function. (PMID:20675372)
• The truncated monomeric form of LIS1 had little effect on dynein motility, but an artificial dimer of truncated LIS1 suppressed dynein motility, which was restored by the N-terminal fragment of NDEL1. (PMID:21036906)
• Lis1 is cell-autonomously required for cortical neuron and astrocyte production and is involved in neuronal migration. (PMID:21092859)
• Single nucleotide polymorphism in PAFAH1B1 gene is associated with Myelodysplastic Syndromes. (PMID:21107783)
• these results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of hepatocellular carcinoma. (PMID:21569763)
• PAFAH Ib regulates endocytic membrane trafficking through novel mechanisms involving both PLA(2) activity and LIS1-dependent dynein function (PMID:21593204)
• we have identified a so-far-unknown interaction between LIS1 and PDE4 isoforms, whereby PDE4 can modulate LIS1-dynein complexes and dynein-dependent processes within cells by sequestering LIS1. (PMID:21652625)
• The results did not detect a significant association. It indicated that common genetic variations in LIS1 genes might not play a role in the genetic predisposition to autism. (PMID:21890215)
• Mutually exclusive cytoplasmic dynein regulation by NudE-Lis1 and dynactin. (PMID:21911489)
• cell type-restricted role for LIS1 in large vesicular transport and quantitative support for a general role for LIS1 in high-load dynein functions. (PMID:22006948)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pafah1b1b	ENSDARG00000026595
danio_rerio	pafah1b1a	ENSDARG00000032013
mus_musculus	Pafah1b1	ENSMUSG00000020745
rattus_norvegicus	Pafah1b1	ENSRNOG00000002755
drosophila_melanogaster	Lis-1	FBGN0015754
caenorhabditis_elegans		WBGENE00003047

Paralogs (26): SNRNP40 (ENSG00000060688), WDR62 (ENSG00000075702), WDR7 (ENSG00000091157), TBL2 (ENSG00000106638), PAK1IP1 (ENSG00000111845), WDR75 (ENSG00000115368), DCAF4 (ENSG00000119599), DAW1 (ENSG00000123977), TEP1 (ENSG00000129566), AHI1 (ENSG00000135541), WDR38 (ENSG00000136918), MAPKBP1 (ENSG00000137802), POC1B (ENSG00000139323), NEDD1 (ENSG00000139350), COP1 (ENSG00000143207), WDR17 (ENSG00000150627), WDR43 (ENSG00000163811), POC1A (ENSG00000164087), WDR88 (ENSG00000166359), WDR81 (ENSG00000167716), DCAF4L2 (ENSG00000176566), DCAF4L1 (ENSG00000182308), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

Platelet-activating factor acetylhydrolase IB subunit beta — P43034 (reviewed: P43034)

Alternative names: Lissencephaly-1 protein, PAF acetylhydrolase 45 kDa subunit, PAF-AH alpha

All UniProt accessions (12): P43034, A0A6Q8PFT2, A0A6Q8PFU3, A0A6Q8PG63, A0A6Q8PGF8, A0A6Q8PH33, A0AAQ5BGM1, A0AAQ5BGP0, A0AAQ5BGP7, A0AAQ5BH67, I3L3N5, I3L495

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner. Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos. May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR.

Subunit / interactions. Component of the cytosolic PAF-AH (I) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity. Interacts with the catalytic dimer of PAF-AH (I) heterotetrameric enzyme: interacts with PAFAH1B2 homodimer (alpha2/alpha2 homodimer), PAFAH1B3 homodimer (alpha1/alpha1 homodimer) and PAFAH1B2-PAFAH1B3 heterodimer (alpha2/alpha1 heterodimer). Interacts with IQGAP1, KATNB1 and NUDC. Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling. Can self-associate. Interacts with DCX, dynein, dynactin, NDE1, NDEL1 and RSN. Interacts with DISC1, and this interaction is enhanced by NDEL1. Interacts with INTS13. Interacts with DCDC1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Nucleus membrane.

Tissue specificity. Fairly ubiquitous expression in both the frontal and occipital areas of the brain.

Disease relevance. Lissencephaly 1 (LIS1) [MIM:607432] A classical lissencephaly. It is characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. Associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum. The disease is caused by variants affecting the gene represented in this entry. Subcortical band heterotopia (SBH) [MIM:607432] SBH is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal. The disease is caused by variants affecting the gene represented in this entry. Miller-Dieker lissencephaly syndrome (MDLS) [MIM:247200] A contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly and distinct facial features. Additional congenital malformations can be part of the condition. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Dimerization mediated by the LisH domain may be required to activate dynein.

Miscellaneous. Originally the subunits of the type I platelet-activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (Ref.4). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively.

Similarity. Belongs to the WD repeat LIS1/nudF family.

Isoforms (2)

UniProt ID	Names	Canonical?
P43034-1	1	yes
P43034-2	2

RefSeq proteins (1): NP_000421* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR006594	LisH	Conserved_site
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR017252	Dynein_regulator_LIS1	Family
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR037190	LIS1_N	Homologous_superfamily
IPR050349	WD_LIS1/nudF_dynein_reg	Family
IPR056795	PAC1-like_LisH-like_dom	Domain

Pfam: PF00400, PF24951

UniProt features (68 total): strand 28, repeat 7, sequence variant 7, region of interest 6, turn 5, splice variant 4, sequence conflict 3, helix 3, modified residue 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
7MT1	X-RAY DIFFRACTION	1.3
9E0Z	ELECTRON MICROSCOPY	2.86
9E11	ELECTRON MICROSCOPY	2.86
9DZY	ELECTRON MICROSCOPY	3.1
9E0T	ELECTRON MICROSCOPY	3.1
8FDT	ELECTRON MICROSCOPY	3.2
9E0W	ELECTRON MICROSCOPY	3.2
8FDU	ELECTRON MICROSCOPY	3.3
9E22	ELECTRON MICROSCOPY	3.3
8PQY	ELECTRON MICROSCOPY	3.8
9YNC	ELECTRON MICROSCOPY	3.93
8DYV	ELECTRON MICROSCOPY	3.97
8DYU	ELECTRON MICROSCOPY	4
8PQW	ELECTRON MICROSCOPY	4.2
9YND	ELECTRON MICROSCOPY	4.26
9E13	ELECTRON MICROSCOPY	4.5
9E14	ELECTRON MICROSCOPY	5
8PQZ	ELECTRON MICROSCOPY	5.5
9YNH	ELECTRON MICROSCOPY	5.5
9YNE	ELECTRON MICROSCOPY	8.46
8PTK	ELECTRON MICROSCOPY	10

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43034-F1	90.42	0.67

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 (2): 53, 109

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition

MSigDB gene sets: 819 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, ATF_B, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_DENDRITE_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_COGNITION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_NEURON_PROJECTION_EXTENSION

GO Biological Process (62): establishment of mitotic spindle orientation (GO:0000132), microtubule cytoskeleton organization (GO:0000226), ameboidal-type cell migration (GO:0001667), acrosome assembly (GO:0001675), neuron migration (GO:0001764), positive regulation of cytokine-mediated signaling pathway (GO:0001961), microtubule-based process (GO:0007017), nuclear migration (GO:0007097), JNK cascade (GO:0007254), chemical synaptic transmission (GO:0007268), germ cell development (GO:0007281), neuroblast proliferation (GO:0007405), learning or memory (GO:0007611), retrograde axonal transport (GO:0008090), adult locomotory behavior (GO:0008344), protein secretion (GO:0009306), negative regulation of neuron projection development (GO:0010977), lipid catabolic process (GO:0016042), stem cell division (GO:0017145), transmission of nerve impulse (GO:0019226), corpus callosum morphogenesis (GO:0021540), hippocampus development (GO:0021766), layer formation in cerebral cortex (GO:0021819), cerebral cortex neuron differentiation (GO:0021895), cerebral cortex development (GO:0021987), actin cytoskeleton organization (GO:0030036), microtubule organizing center organization (GO:0031023), osteoclast development (GO:0036035), reelin-mediated signaling pathway (GO:0038026), positive regulation of embryonic development (GO:0040019), establishment of planar polarity of embryonic epithelium (GO:0042249), cortical microtubule organization (GO:0043622), positive regulation of axon extension (GO:0045773), positive regulation of mitotic cell cycle (GO:0045931), negative regulation of JNK cascade (GO:0046329), platelet activating factor metabolic process (GO:0046469), vesicle transport along microtubule (GO:0047496), brain morphogenesis (GO:0048854), modulation of chemical synaptic transmission (GO:0050804), neuromuscular process controlling balance (GO:0050885)

GO Molecular Function (12): microtubule binding (GO:0008017), heparin binding (GO:0008201), dynactin binding (GO:0034452), identical protein binding (GO:0042802), phospholipase binding (GO:0043274), dynein intermediate chain binding (GO:0045505), protein heterodimerization activity (GO:0046982), microtubule plus-end binding (GO:0051010), phosphoprotein binding (GO:0051219), dynein complex binding (GO:0070840), protein binding (GO:0005515), protein-containing complex binding (GO:0044877)

GO Cellular Component (34): astral microtubule (GO:0000235), kinetochore (GO:0000776), nuclear envelope (GO:0005635), centrosome (GO:0005813), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule associated complex (GO:0005875), cytoplasmic microtubule (GO:0005881), cell cortex (GO:0005938), 1-alkyl-2-acetylglycerophosphocholine esterase complex (GO:0008247), cell leading edge (GO:0031252), motile cilium (GO:0031514), nuclear membrane (GO:0031965), stereocilium (GO:0032420), neuron projection (GO:0043005), neuronal cell body (GO:0043025), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), central region of growth cone (GO:0090724), sperm midpiece (GO:0097225), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), axon cytoplasm (GO:1904115), nucleus (GO:0005634), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), axon (GO:0030424), growth cone (GO:0030426), vesicle (GO:0031982), transferase complex (GO:1990234)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	3
G2/M Transition	2
Centrosome maturation	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
Golgi-to-ER retrograde transport	1
M Phase	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
protein binding	3
cell migration	2
developmental process involved in reproduction	2
cellular process involved in reproduction in multicellular organism	2
generation of neurons	2
binding	2
nucleus	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
cytoskeleton organization	1
microtubule-based process	1
spermatid development	1
cellular component assembly involved in morphogenesis	1
secretory granule organization	1
organelle assembly	1
regulation of cytokine-mediated signaling pathway	1
positive regulation of signal transduction	1
cytokine-mediated signaling pathway	1
positive regulation of response to cytokine stimulus	1
cellular process	1
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
MAPK cascade	1
anterograde trans-synaptic signaling	1
gamete generation	1
cell development	1
neural precursor cell proliferation	1
behavior	1
cognition	1
axonal transport	1
axon cytoplasm	1
locomotory behavior	1
adult behavior	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1

Protein interactions and networks

STRING

2260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAFAH1B1	NDEL1	Q9GZM8	988
PAFAH1B1	NDE1	Q9NXR1	957
PAFAH1B1	PAFAH1B2	P68402	951
PAFAH1B1	YWHAE	P29360	944
PAFAH1B1	PAFAH1B3	Q15102	940
PAFAH1B1	NUDC	Q9Y266	924
PAFAH1B1	DISC1	Q9NRI5	841
PAFAH1B1	PAFAH2	Q99487	838
PAFAH1B1	PITPNA	Q00169	804
PAFAH1B1	TUBA1B	P04687	798
PAFAH1B1	CLIP1	P30622	792
PAFAH1B1	TRARG1	Q8IXB3	770
PAFAH1B1	RMND5A	Q9H871	764
PAFAH1B1	BHLHA9	Q7RTU4	757
PAFAH1B1	SCARF1	Q14162	754

IntAct

127 interactions, top by confidence:

A	B	Type	Score
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
PAFAH1B1	NDEL1	psi-mi:“MI:0915”(physical association)	0.790
NDEL1	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PAFAH1B2	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.700
PAFAH1B2	PAFAH1B1	psi-mi:“MI:0914”(association)	0.700
PAFAH1B1	DISC1	psi-mi:“MI:0915”(physical association)	0.680
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
PAFAH1B1	Nde1	psi-mi:“MI:0915”(physical association)	0.650
Nde1	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.650
DYNLT1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.640
GID8	PGRMC2	psi-mi:“MI:0914”(association)	0.640
NUDCD2	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.640
PAFAH1B3	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
PAFAH1B3	PAFAH1B1	psi-mi:“MI:0914”(association)	0.640
NUDCD2	HSP90AA1	psi-mi:“MI:0914”(association)	0.610
PAFAH1B1	HSP90AA1	psi-mi:“MI:0914”(association)	0.610
HSP90AA1	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.610
GID8	HTRA2	psi-mi:“MI:0914”(association)	0.610

BioGRID (794): PAFAH1B1 (Affinity Capture-MS), AP1G1 (Co-fractionation), ASNS (Co-fractionation), CHID1 (Co-fractionation), CHMP2B (Co-fractionation), CSTF1 (Co-fractionation), DYNC1H1 (Co-fractionation), SBDS (Co-fractionation), SCLY (Co-fractionation), PAFAH1B1 (Affinity Capture-MS), DYNC1I1 (Affinity Capture-Western), PAFAH1B1 (Proximity Label-MS), PAFAH1B1 (Proximity Label-MS), PAFAH1B1 (Proximity Label-MS), PAFAH1B1 (Affinity Capture-MS)

ESM2 similar proteins: A1CUD6, A4R3M4, A7S338, B0LSW3, B0XM00, B2AEZ5, B2VWG7, B3MEY6, B3NPW0, B3S4I5, B4GAJ1, B4HSL3, B4JWA1, B4KT48, B4LQ21, B4MY65, B4P6P9, B4QHG6, B5X3C4, B5X3Z6, B6HP56, B7PS00, C3XVT5, C4Q0P6, C5FWH1, C5PFX0, D1ZEB4, D3TLL6, D4AZ50, D4DG66, P43033, P43034, P63004, P63005, Q0U1B1, Q17N69, Q291L9, Q4ICM0, Q4RJN5, Q4WLM7

Diamond homologs: A0CH87, A0DB19, A1CF18, A1CUD6, A7S338, A8NEG8, A8XZJ9, A9V790, B0LSW3, B0XM00, B2AEZ5, B2B766, B2VWG7, B3MEY6, B3NPW0, B3S4I5, B4GAJ1, B4HSL3, B4JWA1, B4KT48, B4LQ21, B4MY65, B4P6P9, B4QHG6, B5X3C4, B5X3Z6, B6GZD3, B6HP56, B6QC06, B7FNU7, B7PS00, B8N9H4, B8P4B0, B8PD53, B9WD30, C0NRC6, C0S902, C1GB49, C3XVT5, C4Q0P6

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
DISC1	“up-regulates activity”	PAFAH1B1	binding
PAFAH1B1	up-regulates	Cerebral_cortex_development
PAFAH1B1	“up-regulates activity”	CLIP1	binding
NUDCD2	“up-regulates quantity by stabilization”	PAFAH1B1	binding
HSP90AA1	“up-regulates quantity by stabilization”	PAFAH1B1	binding
PAFAH1B1	up-regulates	Neuron_migration
PAFAH1B1	“up-regulates activity”	NDEL1	binding
PAFAH1B1	“up-regulates activity”	DYNC1H1	binding
GDNF	“down-regulates quantity by repression”	PAFAH1B1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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
Activation of BAD and translocation to mitochondria	5	48.2×	8e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	42.5×	1e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	42.5×	1e-06
Aggrephagy	11	34.6×	3e-13
COPI-independent Golgi-to-ER retrograde traffic	13	34.2×	3e-15
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	13	31.9×	8e-15
Activation of BH3-only proteins	5	31.4×	7e-06
Loss of Nlp from mitotic centrosomes	13	26.1×	8e-14

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of microtubule polymerization	5	35.1×	3e-05
microtubule nucleation	5	32.5×	4e-05
establishment of mitotic spindle orientation	6	30.1×	7e-06
microtubule-based movement	8	24.6×	6e-07
cellular response to heat	6	21.5×	4e-05
protein targeting	5	19.1×	5e-04
mitotic spindle organization	5	14.2×	2e-03
microtubule cytoskeleton organization	9	11.4×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	140
Likely pathogenic	56
Uncertain significance	160
Likely benign	178
Benign	38

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1077134	NM_000430.4(PAFAH1B1):c.368T>A (p.Met123Lys)	Pathogenic
1164013	NM_000430.4(PAFAH1B1):c.1136A>G (p.His379Arg)	Pathogenic
1214157	NM_000430.4(PAFAH1B1):c.117+1G>C	Pathogenic
1338362	NM_000430.4(PAFAH1B1):c.708G>A (p.Trp236Ter)	Pathogenic
1338383	NM_000430.4(PAFAH1B1):c.247_250dup (p.Pro84fs)	Pathogenic
1338599	NM_000430.4(PAFAH1B1):c.164G>A (p.Trp55Ter)	Pathogenic
1362377	NM_000430.4(PAFAH1B1):c.643del (p.Thr215fs)	Pathogenic
1398381	NM_000430.4(PAFAH1B1):c.1011del (p.His337fs)	Pathogenic
1399663	NM_000430.4(PAFAH1B1):c.427G>T (p.Glu143Ter)	Pathogenic
1403994	NC_000017.10:g.(?2568646)(2585096_?)del	Pathogenic
1404337	NM_000430.4(PAFAH1B1):c.843C>A (p.Cys281Ter)	Pathogenic
1435082	NC_000017.10:g.(?2573437)(2573645_?)del	Pathogenic
1457753	NM_000430.4(PAFAH1B1):c.794del (p.Thr265fs)	Pathogenic
1458748	NM_000430.4(PAFAH1B1):c.1009_1022del (p.His337fs)	Pathogenic
1458875	NM_000430.4(PAFAH1B1):c.656G>A (p.Trp219Ter)	Pathogenic
159486	NM_000430.4(PAFAH1B1):c.1002+5G>A	Pathogenic
159489	NM_000430.4(PAFAH1B1):c.1009C>T (p.His337Tyr)	Pathogenic
159490	NM_000430.4(PAFAH1B1):c.1024_1031del (p.Arg342fs)	Pathogenic
159491	NM_000430.4(PAFAH1B1):c.1063del (p.Ser355fs)	Pathogenic
159492	NM_000430.4(PAFAH1B1):c.1064G>A (p.Ser355Asn)	Pathogenic
159493	NM_000430.4(PAFAH1B1):c.1100del (p.Tyr367fs)	Pathogenic
159494	NM_000430.4(PAFAH1B1):c.1111C>T (p.Arg371Ter)	Pathogenic
159495	NM_000430.4(PAFAH1B1):c.1135C>T (p.His379Tyr)	Pathogenic
159496	NM_000430.4(PAFAH1B1):c.1159+2T>A	Pathogenic
159497	NM_000430.4(PAFAH1B1):c.1159G>T (p.Asp387Tyr)	Pathogenic
159501	NM_000430.4(PAFAH1B1):c.1196G>C (p.Ser399Thr)	Pathogenic
159502	NM_000430.4(PAFAH1B1):c.1201G>C (p.Asp401His)	Pathogenic
159504	NM_000430.4(PAFAH1B1):c.1233A>C (p.Ter411Cys)	Pathogenic
159505	NM_000430.4(PAFAH1B1):c.136_137del (p.Lys46fs)	Pathogenic
159506	NM_000430.4(PAFAH1B1):c.152del (p.Leu51fs)	Pathogenic

SpliceAI

2226 predictions. Top by Δscore:

Variant	Effect	Δscore
17:2638094:CTTAG:C	acceptor_loss	1.0000
17:2638097:A:AC	acceptor_loss	1.0000
17:2638097:A:AG	acceptor_gain	1.0000
17:2638097:AG:A	acceptor_gain	1.0000
17:2638097:AGGT:A	acceptor_gain	1.0000
17:2638097:AGGTG:A	acceptor_gain	1.0000
17:2638098:G:GT	acceptor_gain	1.0000
17:2638098:GG:G	acceptor_gain	1.0000
17:2638098:GGT:G	acceptor_gain	1.0000
17:2638098:GGTG:G	acceptor_gain	1.0000
17:2638098:GGTGG:G	acceptor_gain	1.0000
17:2638316:GAACT:G	donor_gain	1.0000
17:2638317:AACT:A	donor_gain	1.0000
17:2638317:AACTG:A	donor_loss	1.0000
17:2638318:ACT:A	donor_gain	1.0000
17:2638319:CT:C	donor_gain	1.0000
17:2638320:TGTA:T	donor_loss	1.0000
17:2638321:G:GG	donor_gain	1.0000
17:2638321:G:T	donor_loss	1.0000
17:2638322:TAAG:T	donor_loss	1.0000
17:2665366:TTTCA:T	acceptor_loss	1.0000
17:2665367:TTCAG:T	acceptor_loss	1.0000
17:2665368:TCAG:T	acceptor_loss	1.0000
17:2665370:A:AG	acceptor_gain	1.0000
17:2665371:G:GG	acceptor_gain	1.0000
17:2665371:G:GT	acceptor_loss	1.0000
17:2665371:GA:G	acceptor_gain	1.0000
17:2665371:GAA:G	acceptor_gain	1.0000
17:2665439:G:GT	donor_gain	1.0000
17:2665453:TGTGG:T	donor_loss	1.0000

AlphaMissense

2702 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:2638320:T:C	L11P	1.000
17:2665379:G:C	A14P	1.000
17:2665395:T:C	L19P	1.000
17:2666050:T:C	L51S	1.000
17:2666061:T:A	W55R	1.000
17:2666061:T:C	W55R	1.000
17:2666063:G:C	W55C	1.000
17:2666063:G:T	W55C	1.000
17:2666071:T:A	V58D	1.000
17:2667086:C:A	P96H	1.000
17:2667131:T:A	V111D	1.000
17:2667178:T:C	S127P	1.000
17:2667184:G:C	D129H	1.000
17:2670166:T:A	W135R	1.000
17:2670166:T:C	W135R	1.000
17:2670221:T:A	V153E	1.000
17:2670262:T:C	S167P	1.000
17:2670263:C:A	S167Y	1.000
17:2670263:C:T	S167F	1.000
17:2670266:G:A	C168Y	1.000
17:2670267:T:G	C168W	1.000
17:2670269:C:A	S169Y	1.000
17:2670269:C:T	S169F	1.000
17:2670274:G:C	D171H	1.000
17:2670275:A:T	D171V	1.000
17:2670292:T:A	W177R	1.000
17:2670292:T:C	W177R	1.000
17:2670294:G:C	W177C	1.000
17:2670294:G:T	W177C	1.000
17:2672668:T:A	N194K	1.000

dbSNP variants (sampled 300 via entrez): RS1000000148 (17:2599450 G>A), RS1000046818 (17:2636423 T>C), RS1000047823 (17:2641555 A>T), RS1000060092 (17:2648159 G>A), RS1000060156 (17:2644994 C>G), RS1000080168 (17:2641776 A>G), RS1000123451 (17:2677711 G>A,T), RS1000157395 (17:2662498 G>A,C), RS1000162173 (17:2604536 C>A,T), RS1000170739 (17:2673604 A>C), RS1000198346 (17:2620279 C>A,T), RS1000217132 (17:2612989 A>G), RS1000240502 (17:2678556 ACT>A), RS1000278617 (17:2604707 A>G), RS1000314561 (17:2678344 G>C)

Disease associations

OMIM: gene MIM:601545 | disease phenotypes: MIM:607432, MIM:192350, MIM:619681

GenCC curated gene-disease

Disease	Classification	Inheritance
lissencephaly due to LIS1 mutation	Definitive	Autosomal dominant

Mondo (7): lissencephaly due to LIS1 mutation (MONDO:0011830), intellectual disability (MONDO:0001071), VACTERL/vater association (MONDO:0008642), lissencephaly spectrum disorders (MONDO:0018838), classic lissencephaly (MONDO:0015146), dystonia, early-onset, and/or spastic paraplegia (MONDO:0859215), subcortical band heterotopia (MONDO:0020491)

Orphanet (6): Lissencephaly due to LIS1 mutation (Orphanet:95232), VACTERL/VATER association (Orphanet:887), Lissencephaly (Orphanet:48471), Classic lissencephaly (Orphanet:102009), Subcortical band heterotopia (Orphanet:99796), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000112	Nephropathy
HP:0000160	Narrow mouth
HP:0000177	Abnormal upper lip morphology
HP:0000218	High palate
HP:0000253	Progressive microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000960	Sacral dimple
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001273	Abnormal corpus callosum morphology
HP:0001285	Spastic tetraparesis
HP:0001302	Pachygyria
HP:0001319	Neonatal hypotonia
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001339	Lissencephaly

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003770_32	Neuroticism	9.000000e-09
GCST004158_2	Self-reported tiredness	7.000000e-08
GCST006940_22	Neurociticism	8.000000e-12
GCST009028_6	Adverse response to drug	7.000000e-07
GCST012354_51	Anxiety	2.000000e-11
GCST012355_15	Depression	1.000000e-07
GCST90002395_236	Mean platelet volume	3.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0007946	tiredness measurement
EFO:0009658	adverse effect
EFO:0009863	anxiety measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	8
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
bisphenol A	increases expression	2
sodium arsenite	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Lead	affects splicing, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression, increases expression	1
beta-lapachone	increases expression	1
methylparaben	decreases expression, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	decreases methylation	1
chloropicrin	increases expression	1
deguelin	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

198 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
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
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
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)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders