DPP3

Chr 11

dipeptidyl peptidase 3

Also known as: DPPIII

NCBI Gene: 10072 ENSG00000254986 UniProt: Q9NY33

DPP3 encodes a cytoplasmic metallopeptidase that cleaves bioactive peptides including angiotensin and enkephalins using its zinc-binding motif. Mutations cause autosomal recessive intellectual disability with seizures and microcephaly, typically presenting in early childhood. The gene is extremely intolerant to loss-of-function variants, indicating it is essential for normal neurodevelopment.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is a member of the M49 family of metallopeptidases. This cytoplasmic protein binds a single zinc ion with its zinc-binding motif (HELLGH) and has post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Increased activity of this protein is associated with endometrial and ovarian cancers. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2012]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

—

Mechanism

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?

0.81LOEUF

pLI 0.000

Z-score 2.54

OE 0.57 (0.41–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.29Z-score

OE missense 0.83 (0.77–0.91)

387 obs / 465.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.41–0.81)

0≤0.351.4

Missense OE?0.83 (0.77–0.91)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 23 / 40.4Missense obs/exp: 387 / 465.1Syn Z: 0.62

Background carrier burden — how many people carry a rare variant somewhere in DPP3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

912 rare PASS variants

Rare truncating (LoF)

1 in 910

158 rare PASS variants

Rare synonymous (reference)

1 in 120

403 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DPP3. 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 64	1 in 870
South Asian	~43k	1 in 59	1 in 830
Remaining (unassigned)	~30k	1 in 41	1 in 1,200
European (Finnish)	~27k	1 in 280	1 in 5,300
Admixed American	~22k	1 in 52	1 in 670
African / African American	~21k	1 in 45	1 in 550
East Asian	~20k	1 in 50	1 in 1,200
Ashkenazi Jewish	~13k	1 in 230	1 in 1,300
Middle Eastern	~2,884	1 in 67	1 in 350

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 17 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 17.? see exons ↓