PROSER1

Chr 13

proline and serine rich 1

Also known as: C13orf23

The protein mediates OGT interaction with and O-GlcNAcylation of TET2 to control TET2 stabilization at enhancers and CpG islands. Mutations cause autosomal recessive neurodevelopmental disorder with intellectual disability and dysmorphic features. The gene shows significant constraint against loss-of-function variants (LOEUF 0.389), suggesting intolerance to protein disruption.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.39
Clinical SummaryPROSER1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 135 VUS of 224 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.711
Z-score 4.10
OE 0.20 (0.110.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.14Z-score
OE missense 0.98 (0.911.06)
492 obs / 500.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.110.39)
00.351.4
Missense OE0.98 (0.911.06)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 6 / 30.4Missense obs/exp: 492 / 500.7Syn Z: -0.78
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPROSER1-related developmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3594th %ile
GOF
0.2696th %ile
LOF
0.67top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

224 submitted variants in ClinVar

Classification Summary

Pathogenic49
VUS135
Likely Benign8
Benign3
49
Pathogenic
135
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
0
0
0
0
0
VUS
2
127
6
0
135
Likely Benign
0
5
0
3
8
Benign
0
1
0
2
3
Total2133555195

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

View in ClinVar →

Protein Context — Lollipop Plot

PROSER1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC