PNPLA6

Chr 19AR

patatin like domain 6, lysophospholipase

Also known as: BNHS, LNMS, NTE, NTEMND, OMCS, SPG39, iPLA2delta, sws

The protein is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine and functions in neurite outgrowth and process elongation during neuronal differentiation from its location on the endoplasmic reticulum membrane. Mutations cause autosomal recessive disorders including spastic paraplegia 39, Boucher-Neuhauser syndrome, Oliver-McFarlane syndrome, and possibly Laurence-Moon syndrome. The pathogenic mechanism appears to involve gain-of-function effects.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.644 OMIM phenotypes
Clinical SummaryPNPLA6
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Gene-Disease Validity (ClinGen)
retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.64LOEUF
pLI 0.000
Z-score 4.00
OE 0.48 (0.360.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
4.35Z-score
OE missense 0.59 (0.550.64)
529 obs / 895.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.48 (0.360.64)
00.351.4
Missense OE0.59 (0.550.64)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 33 / 68.8Missense obs/exp: 529 / 895.8Syn Z: -0.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePNPLA6-related retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7034th %ile
GOF
0.75top 25%
LOF
0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PNPLA6 · 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

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 ↗