SPPL2A

Chr 15AR

signal peptide peptidase like 2A

Also known as: IMD86, IMP3, PSL2

NCBI Gene: 84888 ENSG00000138600 UniProt: Q8TCT8 OMIM: 608238

This gene encodes a member of the GXGD family of aspartic proteases, which are transmembrane proteins with two conserved catalytic motifs localized within the membrane-spanning regions, as well as a member of the signal peptide peptidase-like protease (SPPL) family. This protein is expressed in all major adult human tissues and localizes to late endosomal compartments and lysosomal membranes. A pseudogene of this gene also lies on chromosome 15. [provided by RefSeq, Feb 2012]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 86, mycobacteriosisMIM #619549

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Immunodeficiency 86, mycobacteriosis; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in SPPL2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

626 rare PASS variants

Rare truncating (LoF)

1 in 1,700

108 rare PASS variants

Rare synonymous (reference)

1 in 380

216 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPPL2A. 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 130	1 in 1,500
South Asian	~43k	1 in 82	1 in 1,200
Remaining (unassigned)	~30k	1 in 160	1 in 2,600
European (Finnish)	~27k	1 in 160	1 in 4,300
Admixed American	~22k	1 in 130	1 in 2,000
African / African American	~21k	1 in 80	1 in 2,000
East Asian	~20k	1 in 94	1 in 2,300
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	≈ 1 in 1,200

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 15 coding exons well covered in gnomAD exomes; exons 1, 2, 4, 6, 7 and 6 more marginal. Genomes: all 15.? see exons ↓