PPDPF

Chr 20

pancreatic progenitor cell differentiation and proliferation factor

Also known as: C20orf149, dJ697K14.9, exdpf

The protein is a probable regulator of exocrine pancreas development and is predicted to be involved in cell differentiation and TORC1 signaling. This gene is highly constrained against loss-of-function variants (pLI nearly 1.0), but specific disease associations and inheritance patterns have not been established in the current literature. The mitochondrial localization suggests potential involvement in metabolic processes affecting pancreatic function.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in cell differentiation. Predicted to act upstream of or within TORC1 signaling and liver development. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.94

Clinical Summary— PPDPF

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 35 VUS of 46 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.94LOEUF

pLI 0.000

Z-score -0.94

OE 1.57 (0.72–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.37Z-score

OE missense 1.12 (0.94–1.35)

82 obs / 73.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.57 (0.72–1.94)

0≤0.351.4

Missense OE?1.12 (0.94–1.35)

0≤0.61.4

Synonymous OE?1.42

0≤1.21.6

LoF obs/exp: 5 / 3.2Missense obs/exp: 82 / 73.1Syn Z: -1.80

This gene — mechanism propensity

0.6162th %ile

GOF

0.6542th %ile

LOF

0.52top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS35

Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	3	3
Likely Pathogenic	0	0	0	0
VUS	1	31	3	35
Likely Benign	0	0	0	0
Benign	0	0	0	0
Total	1	31	6	38

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

57 pathogenic / likely-pathogenic (of 85) ClinVar copy-number / structural variants overlap PPDPF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →