DPP8

Chr 15

dipeptidyl peptidase 8

Also known as: DP8, DPRP-1, DPRP1, MST097, MSTP097, MSTP135, MSTP141

NCBI Gene: 54878 ENSG00000074603 UniProt: Q6V1X1 OMIM: 606819

This gene encodes a member of the peptidase S9B family, a small family of dipeptidyl peptidases that are able to cleave peptide substrates at a prolyl bond. The encoded protein shares similarity with dipeptidyl peptidase IV in that it is ubiquitously expressed, and hydrolyzes the same substrates. These similarities suggest that, like dipeptidyl peptidase IV, this protein may play a role in T-cell activation and immune function. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.27

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.998

Z-score 5.55

OE 0.14 (0.08–0.27)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.36Z-score

OE missense 0.70 (0.64–0.77)

343 obs / 489.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.08–0.27)

0≤0.351.4

Missense OE?0.70 (0.64–0.77)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 7 / 48.9Missense obs/exp: 343 / 489.7Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in DPP8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 81

948 rare PASS variants

Rare truncating (LoF)

1 in 3,500

70 rare PASS variants

Rare synonymous (reference)

1 in 160

416 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DPP8. 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 3,300
South Asian	~43k	1 in 66	1 in 7,000
Remaining (unassigned)	~30k	1 in 59	≈ 1 in 9,900
European (Finnish)	~27k	1 in 440	≈ 1 in 27,000
Admixed American	~22k	1 in 72	1 in 1,900
African / African American	~21k	1 in 50	1 in 3,000
East Asian	~20k	1 in 79	1 in 1,800
Ashkenazi Jewish	~13k	1 in 560	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 87	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): 12 of 19 coding exons well covered in gnomAD exomes; exons 3, 7, 8, 9, 11 and 2 more marginal. Genomes: all 19.? see exons ↓