PLD6

Chr 17

phospholipase D family member 6

Also known as: ZUC

NCBI Gene: 201164 ENSG00000179598 UniProt: Q8N2A8 OMIM: 614960

PLD6 encodes a phospholipase that cleaves the mitochondrial lipid cardiolipin to regulate mitochondrial fusion and fission dynamics, and also functions as an endonuclease critical for PIWI-interacting RNA biogenesis during spermatogenesis. Mutations cause mitochondrial myopathy and male infertility, with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variation (pLI 0.002, LOEUF 1.76), suggesting complete loss of function may be compatible with survival in some cases.

OMIM ResearchSummary from RefSeq, UniProt

Enables cardiolipin phospholipase D activity and protein homodimerization activity. Involved in mitochondrial fusion and phospholipid biosynthetic process. Acts upstream of or within positive regulation of mitochondrial fusion. Located in mitochondrial outer membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.76

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.76LOEUF

pLI 0.002

Z-score 0.24

OE 0.88 (0.42–1.76)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.02Z-score

OE missense 0.76 (0.65–0.89)

111 obs / 145.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.42–1.76)

0≤0.351.4

Missense OE?0.76 (0.65–0.89)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 4 / 4.6Missense obs/exp: 111 / 145.8Syn Z: 1.08

Background carrier burden — how many people carry a rare variant somewhere in PLD6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

353 rare PASS variants

Rare truncating (LoF)

1 in 930

58 rare PASS variants

Rare synonymous (reference)

1 in 250

168 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLD6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 770
South Asian	~43k	1 in 330	1 in 1,700
Remaining (unassigned)	~30k	1 in 130	1 in 1,500
European (Finnish)	~27k	1 in 1,600	≈ 1 in 7,300
Admixed American	~22k	1 in 160	1 in 4,500
African / African American	~21k	1 in 150	≈ 1 in 5,900
East Asian	~20k	1 in 170	1 in 880
Ashkenazi Jewish	~13k	1 in 1,700	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓