PNPLA6

Chr 19AR

patatin like domain 6, lysophospholipase

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

This gene encodes a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells. Mutations in this gene result in autosomal recessive spastic paraplegia, and the protein is the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Laurence-Moon syndromeMIM #245800
AR
Boucher-Neuhauser syndromeMIM #215470
AR
Oliver-McFarlane syndromeMIM #275400
AR
Spastic paraplegia 39, autosomal recessiveMIM #612020
AR

Clinical highlights

Gene-disease validity (ClinGen)
retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
27
Pubs (1 yr)
P/LP submissions
P/LP missense
0.64
LOEUF
LOF
Mechanism· G2P
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GeneReview available — PNPLA6
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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 OE?0.48 (0.360.64)
00.351.4
Missense OE?0.59 (0.550.64)
00.61.4
Synonymous OE?1.01
01.21.6
LoF obs/exp: 33 / 68.8Missense obs/exp: 529 / 895.8Syn Z: -0.15

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →