PNPLA7

Chr 9

patatin like domain 7, lysophospholipase

Also known as: C9orf111, NTE-R1, NTEL1

NCBI Gene: 375775 ENSG00000130653 UniProt: Q6ZV29

PNPLA7 encodes a lysophospholipase that deacylates lysophosphatidylcholine and other lysophospholipids to generate glycerophosphocholine and regulate lipid metabolism. The gene is not highly constrained against loss-of-function variants and currently has no established disease associations in OMIM or other major clinical databases. No specific inheritance pattern or clinical phenotype has been definitively linked to PNPLA7 mutations at this time.

ResearchSummary from RefSeq, UniProt

Human patatin-like phospholipases, such as PNPLA7, have been implicated in regulation of adipocyte differentiation and have been induced by metabolic stimuli (Wilson et al., 2006 [PubMed 16799181]).[supplied by OMIM, Jun 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.08

Clinical Summary— PNPLA7

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Population Constraint (gnomAD)

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

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ClinVar Variants

272 VUS of 338 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.00

OE 0.87 (0.71–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.69Z-score

OE missense 0.93 (0.88–0.99)

801 obs / 857.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.71–1.08)

0≤0.351.4

Missense OE?0.93 (0.88–0.99)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 61 / 70.0Missense obs/exp: 801 / 857.9Syn Z: -0.54

This gene — mechanism propensity

0.6358th %ile

GOF

0.6247th %ile

LOF

0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

338 submitted variants in ClinVar

ClinVar

Classification Summary

VUS272

Likely Benign29

Benign3

Conflicting1

272

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	271	0	0	272
Likely Benign	0	22	1	6	29
Benign	1	1	0	1	3
Conflicting	—				1
Total	2	294	1	7	305

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

View in ClinVar →

127 pathogenic / likely-pathogenic (of 143) ClinVar copy-number / structural variants overlap PNPLA7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →