ACP6

Chr 1

acid phosphatase 6, lysophosphatidic

Also known as: ACPL1, LPAP, PACPL1

NCBI Gene: 51205 ENSG00000162836 UniProt: Q9NPH0 OMIM: 611471

The protein hydrolyzes lysophosphatidic acid to monoacylglycerol, regulating lipid composition and G protein-coupled receptor signaling pathways. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and brain malformations. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the histidine acid phosphatase protein family. The encoded protein hydrolyzes lysophosphatidic acid, which is involved in G protein-coupled receptor signaling, lipid raft modulation, and in balancing lipid composition within the cell. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

—

Mechanism

📖

GeneReview available — ACP6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score 0.19

OE 0.95 (0.67–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.68Z-score

OE missense 0.88 (0.78–0.98)

206 obs / 235.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.95 (0.67–1.39)

0≤0.351.4

Missense OE?0.88 (0.78–0.98)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 20 / 21.0Missense obs/exp: 206 / 235.2Syn Z: 0.78

Background carrier burden — how many people carry a rare variant somewhere in ACP6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

543 rare PASS variants

Rare truncating (LoF)

1 in 1,200

104 rare PASS variants

Rare synonymous (reference)

1 in 260

194 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACP6. 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 150	1 in 2,000
South Asian	~43k	1 in 95	1 in 780
Remaining (unassigned)	~30k	1 in 75	1 in 470
European (Finnish)	~27k	1 in 420	1 in 1,400
Admixed American	~22k	1 in 110	1 in 990
African / African American	~21k	1 in 140	1 in 1,200
East Asian	~20k	1 in 140	1 in 960
Ashkenazi Jewish	~13k	1 in 280	1 in 1,000
Middle Eastern	~2,884	1 in 92	≈ 1 in 650

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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓