SGPP2

Chr 2

sphingosine-1-phosphate phosphatase 2

Also known as: SPP2, SPPase2

NCBI Gene: 130367 ENSG00000163082 UniProt: Q8IWX5 OMIM: 612827

The protein is a sphingosine-1-phosphate phosphatase that degrades the bioactive signaling molecule sphingosine-1-phosphate, regulating sphingolipid metabolism and inflammatory signaling pathways. Mutations cause autosomal recessive spastic paraplegia with onset typically in childhood or adolescence, characterized by progressive lower limb spasticity and weakness. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a transmembrane protein that degrades the bioactive signaling molecule sphingosine 1-phosphate. The encoded protein is induced during inflammatory responses and has been shown to be downregulated by the microRNA-31 tumor suppressor. Alternative splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.003

Z-score 1.70

OE 0.48 (0.26–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.88–1.11)

193 obs / 195.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.26–0.95)

0≤0.351.4

Missense OE?0.99 (0.88–1.11)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 6 / 12.5Missense obs/exp: 193 / 195.9Syn Z: -1.43

Background carrier burden — how many people carry a rare variant somewhere in SGPP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

495 rare PASS variants

Rare truncating (LoF)

1 in 3,800

75 rare PASS variants

Rare synonymous (reference)

1 in 190

256 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SGPP2. 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 110	1 in 4,200
South Asian	~43k	1 in 120	1 in 2,000
Remaining (unassigned)	~30k	1 in 92	1 in 3,200
European (Finnish)	~27k	1 in 410	≈ 1 in 27,000
Admixed American	~22k	1 in 100	≈ 1 in 5,600
African / African American	~21k	1 in 110	1 in 2,900
East Asian	~20k	1 in 110	1 in 1,500
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 71	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): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓