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GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PAFAH1B1
platelet activating factor acetylhydrolase 1b regulatory subunit 1
Chromosome 17 · 17p13.3
NCBI Gene: 5048Ensembl: ENSG00000007168.15HGNC: HGNC:8574UniProt: A0A6Q8PFT2
219PubMed Papers
23Diseases
0Drugs
185Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTransporter
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nuclear envelopedynein complex bindingestablishment of mitotic spindle orientationextracellular exosomelissencephaly due to LIS1 mutationsubcortical band heterotopiaLissencephalyIntellectual disability
✦AI Summary

PAFAH1B1 encodes the regulatory β-subunit of cytosolic platelet-activating factor acetylhydrolase and is essential for proper neuronal migration during brain development 1. The protein functions as a critical regulator of dynein motor activity and microtubule dynamics, playing a key role in nucleokinesis - the process by which migrating neurons translocate their nuclei toward the centrosome during cortical development 1. Recent structural studies reveal that LIS1 (PAFAH1B1) binds dynactin's p150 subunit and constrains dynein-dynactin interactions to ensure efficient complex formation 2. Mutations in PAFAH1B1 cause classical lissencephaly and subcortical band heterotopia, neurodevelopmental disorders characterized by defective neuronal migration 3. Approximately 60% of patients with classical lissencephaly have deletions or mutations in this gene, with most mutations resulting in truncated proteins 3. Beyond its neurological roles, PAFAH1B1 maintains angiogenic capacity in endothelial cells by regulating Matrix Gla Protein expression 4 and is required for proper spermatogenesis and early embryonic development in humans 5. In cancer contexts, PAFAH1B1 controls cell cycle progression and DNA integrity in triple-negative breast cancer cells, representing a potential therapeutic target 6.

Sources cited
1
PAFAH1B1 is essential for nucleokinesis during neuronal migration and mutations cause lissencephaly
PMID: 11429281
2
LIS1 binds dynactin's p150 subunit and constrains dynein-dynactin complex formation
PMID: 38547289
3
60% of classical lissencephaly patients have PAFAH1B1 mutations, mostly resulting in truncated proteins
PMID: 11754098
4
PAFAH1B1 maintains angiogenic phenotype in endothelial cells by regulating Matrix Gla Protein
PMID: 27124368
5
PAFAH1B1 is required for human spermatogenesis and early embryonic development
PMID: 26380866
6
PAFAH1B1 controls cell cycle progression and DNA integrity in triple-negative breast cancer cells
PMID: 40378956
Disease Associationsⓘ23
lissencephaly due to LIS1 mutationOpen Targets
0.84Strong
subcortical band heterotopiaOpen Targets
0.76Strong
LissencephalyOpen Targets
0.49Moderate
Intellectual disabilityOpen Targets
0.47Moderate
genetic disorderOpen Targets
0.46Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
Myocardial IschemiaOpen Targets
0.39Weak
Abnormality of the skeletal systemOpen Targets
0.39Weak
classic lissencephalyOpen Targets
0.37Weak
Miller-Dieker lissencephaly syndromeOpen Targets
0.37Weak
lissencephaly spectrum disordersOpen Targets
0.37Weak
Neurodevelopmental delayOpen Targets
0.34Weak
Abnormal cortical gyrationOpen Targets
0.34Weak
coronary artery diseaseOpen Targets
0.34Weak
Abnormal cerebral morphologyOpen Targets
0.32Weak
hearing lossOpen Targets
0.28Weak
drug allergyOpen Targets
0.27Weak
placenta praeviaOpen Targets
0.26Weak
cervical carcinomaOpen Targets
0.26Weak
neurotic disorderOpen Targets
0.25Weak
Lissencephaly 1UniProt
Miller-Dieker lissencephaly syndromeUniProt
Subcortical band heterotopiaUniProt
Pathogenic Variants185
NM_000430.4(PAFAH1B1):c.1111C>T (p.Arg371Ter)Pathogenic
Lissencephaly due to LIS1 mutation|Lissencephaly|Neurodevelopmental delay|not provided
★★☆☆2025→ Residue 371
NM_000430.4(PAFAH1B1):c.569-10T>CPathogenic
Lissencephaly due to LIS1 mutation|not provided|Inborn genetic diseases|Lissencephaly
★★☆☆2025
NM_000430.4(PAFAH1B1):c.1050del (p.Lys351fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2025→ Residue 351
NM_000430.4(PAFAH1B1):c.192+1G>APathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2025
NM_000430.4(PAFAH1B1):c.162del (p.Lys54fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2025→ Residue 54
NM_000430.4(PAFAH1B1):c.337C>T (p.Arg113Ter)Pathogenic
not provided|Lissencephaly due to LIS1 mutation
★★☆☆2025→ Residue 113
NM_000430.4(PAFAH1B1):c.647_648del (p.Ile216fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2025→ Residue 216
NM_000430.4(PAFAH1B1):c.484G>A (p.Gly162Ser)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2025→ Residue 162
NM_000430.4(PAFAH1B1):c.817C>T (p.Arg273Ter)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2025→ Residue 273
NM_000430.4(PAFAH1B1):c.537dup (p.Gln180fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2024→ Residue 180
NM_000430.4(PAFAH1B1):c.671+5G>APathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2024
NM_000430.4(PAFAH1B1):c.265C>T (p.Arg89Ter)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2024→ Residue 89
NM_000430.4(PAFAH1B1):c.1018dup (p.Trp340fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2024→ Residue 340
NM_000430.4(PAFAH1B1):c.773_774del (p.Val258fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2024→ Residue 258
NM_000430.4(PAFAH1B1):c.37C>T (p.Arg13Ter)Pathogenic
Lissencephaly due to LIS1 mutation
★★☆☆2024→ Residue 13
NM_000430.4(PAFAH1B1):c.938C>T (p.Ser313Phe)Likely pathogenic
Lissencephaly due to LIS1 mutation
★★☆☆2024→ Residue 313
NM_000430.4(PAFAH1B1):c.430C>T (p.Arg144Ter)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2024→ Residue 144
NM_000430.4(PAFAH1B1):c.347dup (p.His117fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided
★★☆☆2024→ Residue 117
NM_000430.4(PAFAH1B1):c.22C>T (p.Arg8Ter)Pathogenic
Lissencephaly due to LIS1 mutation|Subcortical band heterotopia|Intellectual disability|Lissencephaly|not provided
★★☆☆2024→ Residue 8
NM_000430.4(PAFAH1B1):c.162dup (p.Trp55fs)Pathogenic
Lissencephaly due to LIS1 mutation|not provided|Intellectual disability|not specified
★★☆☆2024→ Residue 55
View on ClinVar ↗
Related Genes
DCTN2Protein interaction100%DCTN4Protein interaction100%ACTR1AProtein interaction100%CDC20Protein interaction100%DCTN3Protein interaction100%KIF1AProtein interaction99%
Tissue Expression6 tissues
Brain
100%
Heart
58%
Lung
40%
Ovary
32%
Liver
21%
Bone Marrow
18%
Gene Interaction Network
Click a node to explore
PAFAH1B1DCTN2DCTN4ACTR1ACDC20DCTN3KIF1A
PROTEIN STRUCTURE
Preparing viewer…
PDB7MT1 · 1.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.10Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.00 [0.00–0.10]
RankingsWhere PAFAH1B1 stands among ~20K protein-coding genes
  • #1,884of 20,598
    Most Researched219 · top 10%
  • #379of 5,498
    Most Pathogenic Variants185 · top 10%
  • #59of 17,882
    Most Constrained (LOEUF)0.10 · top 1%
Genes detectedPAFAH1B1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Mechanism of spindle pole organization and instability in human oocytes.
PMID: 35143306
Science · 2022
1.00
2
Molecular mechanism of dynein-dynactin complex assembly by LIS1.
PMID: 38547289
Science · 2024
0.90
3
Neuronal migration.
PMID: 11429281
Mech Dev · 2001
0.80
4
PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells.
PMID: 27124368
Acta Physiol (Oxf) · 2016
0.70
5
Capturing disease severity in LIS1-lissencephaly reveals proteostasis dysregulation in patient-derived forebrain organoids.
PMID: 41083500
Nat Commun · 2025
0.60