PAFAH1B1

Chr 17AD

platelet activating factor acetylhydrolase 1b regulatory subunit 1

Also known as: LIS1, LIS2, MDCR, MDS, NudF, PAFAH

NCBI Gene: 5048ENSG00000007168UniProt: P43034OMIM: 601545

The protein functions as the non-catalytic alpha subunit of intracellular platelet-activating factor acetylhydrolase Ib, which catalyzes the removal of acetyl groups from platelet-activating factor and localizes to the cytoskeleton. Loss-of-function mutations cause lissencephaly 1 and subcortical laminar heterotopia through autosomal dominant inheritance, with deletions also associated with Miller-Dieker lissencephaly syndrome.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.112 OMIM phenotypes
Clinical Summary— PAFAH1B1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
163 unique Pathogenic / Likely Pathogenic· 143 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — PAFAH1B1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 4.89
OE 0.00 (0.00–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.53Z-score
OE missense 0.35 (0.29–0.42)
81 obs / 232.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.11)
0≤0.351.4
Missense OE0.35 (0.29–0.42)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 0 / 27.9Missense obs/exp: 81 / 232.3Syn Z: 0.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePAFAH1B1-related lissencephalyLOFAD
DN
0.2898th %ile
GOF
0.2796th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 39% of P/LP variants are LoF · LOEUF 0.11

Literature Evidence

LOFPAFAH1B1 haploinsufficiency disrupts GABA neurons and synaptic E/I balance in the dentate gyrus.PMID:29692423

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic129
Likely Pathogenic34
VUS143
Likely Benign158
Benign18
Conflicting7
129
Pathogenic
34
Likely Pathogenic
143
VUS
158
Likely Benign
18
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
52
17
60
0
129
Likely Pathogenic
12
15
7
0
34
VUS
3
109
30
1
143
Likely Benign
0
10
73
75
158
Benign
0
2
14
2
18
Conflicting
—7
Total6715318478489

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PAFAH1B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients