SERP2

Chr 13

stress associated endoplasmic reticulum protein family member 2

Also known as: C13orf21, bA269C23.1

NCBI Gene: 387923 ENSG00000151778 UniProt: Q8N6R1

SERP2 encodes a protein that protects unfolded proteins from degradation during endoplasmic reticulum stress and facilitates their glycosylation, playing a critical role in the ER unfolded protein response. Mutations cause autosomal recessive progressive encephalopathy with brain atrophy, characterized by early-onset developmental regression, seizures, and neurodegeneration. The gene shows moderate constraint against loss-of-function variants, consistent with its essential cellular function in protein quality control.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in endoplasmic reticulum unfolded protein response. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.83

LOEUF

Multiple*

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?

0.83LOEUF

pLI 0.668

Z-score 1.76

OE 0.00 (0.00–0.83)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.92Z-score

OE missense 0.56 (0.39–0.82)

19 obs / 34.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.83)

0≤0.351.4

Missense OE?0.56 (0.39–0.82)

0≤0.61.4

Synonymous OE?1.66

0≤1.21.6

LoF obs/exp: 0 / 3.6Missense obs/exp: 19 / 34.1Syn Z: -1.81

Background carrier burden — how many people carry a rare variant somewhere in SERP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,100

86 rare PASS variants

Rare truncating (LoF)

1 in 11,000

16 rare PASS variants

Rare synonymous (reference)

1 in 900

48 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SERP2. 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 380	1 in 12,000
South Asian	~43k	1 in 450	≈ 1 in 17,000
Remaining (unassigned)	~30k	1 in 280	≈ 1 in 10,000
European (Finnish)	~27k	1 in 1,300	none seen
Admixed American	~22k	1 in 510	≈ 1 in 8,400
African / African American	~21k	1 in 740	1 in 2,000
East Asian	~20k	1 in 500	none seen
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,883	≈ 1 in 1,400	none seen

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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓