PTF1A

Chr 10AR

pancreas associated transcription factor 1a

Also known as: PACA, PAGEN2, PTF1-p48, bHLHa29, p48

This gene encodes a transcription factor that binds E-box sequences and is essential for pancreatic development, determining cell fate in pancreatic buds and maintaining exocrine pancreas gene expression, while also playing important roles in cerebellar and retinal development. Mutations cause autosomal recessive pancreatic agenesis with or without cerebellar agenesis, representing severe developmental disorders affecting multiple organ systems. The gene has moderate constraint against loss-of-function variants and is associated with early developmental phenotypes.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Pancreatic agenesis 2MIM #615935
AR
Pancreatic and cerebellar agenesisMIM #609069
AR
1
Active trials
21
Pubs (1 yr)
19
P/LP submissions
6%
P/LP missense
1.01
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPTF1A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 84 VUS of 186 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — PTF1A
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.166
Z-score 1.57
OE 0.32 (0.131.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.51Z-score
OE missense 0.86 (0.721.02)
88 obs / 102.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.131.01)
00.351.4
Missense OE0.86 (0.721.02)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 2 / 6.2Missense obs/exp: 88 / 102.5Syn Z: -1.08

ClinVar Variant Classifications

186 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS84
Likely Benign56
Benign20
Conflicting8
13
Pathogenic
3
Likely Pathogenic
84
VUS
56
Likely Benign
20
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
10
0
13
Likely Pathogenic
1
1
1
0
3
VUS
3
72
9
0
84
Likely Benign
0
5
1
50
56
Benign
0
0
19
1
20
Conflicting
8
Total7784051184

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

View in ClinVar →

Protein Context — Lollipop Plot

PTF1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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