PROSER2

Chr 10

proline and serine rich 2

Also known as: C10orf47

NCBI Gene: 254427 ENSG00000148426 UniProt: Q86WR7

The protein functions as a proline and serine-rich nuclear protein involved in transcriptional regulation. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.78

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -0.35

OE 1.13 (0.69–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.98Z-score

OE missense 1.19 (1.07–1.32)

250 obs / 209.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.69–1.78)

0≤0.351.4

Missense OE?1.19 (1.07–1.32)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 10 / 8.9Missense obs/exp: 250 / 209.9Syn Z: -0.32

Background carrier burden — how many people carry a rare variant somewhere in PROSER2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

858 rare PASS variants

Rare truncating (LoF)

1 in 530

151 rare PASS variants

Rare synonymous (reference)

1 in 94

386 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PROSER2. 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 56	1 in 960
South Asian	~43k	1 in 50	1 in 490
Remaining (unassigned)	~30k	1 in 40	1 in 1,200
European (Finnish)	~27k	1 in 160	1 in 2,800
Admixed American	~22k	1 in 69	1 in 1,100
African / African American	~21k	1 in 44	1 in 940
East Asian	~20k	1 in 90	1 in 1,700
Ashkenazi Jewish	~13k	1 in 200	1 in 2,400
Middle Eastern	~2,884	1 in 43	≈ 1 in 820

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): 2 of 3 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 3.? see exons ↓