PROSER1

Chr 13

proline and serine rich 1

Also known as: C13orf23

NCBI Gene: 80209 ENSG00000120685 UniProt: Q86XN7

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a conserved protein containing proline and serine rich regions. These regions may be important in protein-protein interactions. [provided by RefSeq, Aug 2012]

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.711

Z-score 4.10

OE 0.20 (0.11–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.14Z-score

OE missense 0.98 (0.91–1.06)

492 obs / 500.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.11–0.39)

0≤0.351.4

Missense OE?0.98 (0.91–1.06)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 6 / 30.4Missense obs/exp: 492 / 500.7Syn Z: -0.78

Background carrier burden — how many people carry a rare variant somewhere in PROSER1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 55

1,204 rare PASS variants

Rare truncating (LoF)

1 in 3,500

103 rare PASS variants

Rare synonymous (reference)

1 in 110

526 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PROSER1. 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 82	1 in 3,700
South Asian	~43k	1 in 40	1 in 3,600
Remaining (unassigned)	~30k	1 in 43	1 in 3,300
European (Finnish)	~27k	1 in 310	≈ 1 in 8,900
Admixed American	~22k	1 in 49	1 in 2,400
African / African American	~21k	1 in 48	≈ 1 in 4,600
East Asian	~20k	1 in 68	1 in 2,100
Ashkenazi Jewish	~13k	1 in 160	1 in 2,600
Middle Eastern	~2,884	1 in 48	≈ 1 in 1,400

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): 9 of 13 coding exons well covered in gnomAD exomes; exons 2, 4, 5, 10 marginal. Genomes: all 13.? see exons ↓