PRR27

Chr 4

proline rich 27

Also known as: C4orf40

NCBI Gene: 401137 ENSG00000187533 UniProt: Q6MZM9

PRR27 encodes a protein located in extracellular exosomes, though its specific molecular function remains unclear. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy, characterized by early-onset seizures and developmental delay. The gene shows tolerance to loss-of-function variants in the general population, consistent with the recessive inheritance pattern observed in affected individuals.

ResearchSummary from RefSeq

Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.64

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.64LOEUF

pLI 0.000

Z-score 0.34

OE 0.86 (0.47–1.64)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.40Z-score

OE missense 1.10 (0.96–1.27)

132 obs / 119.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.47–1.64)

0≤0.351.4

Missense OE?1.10 (0.96–1.27)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 6 / 7.0Missense obs/exp: 132 / 119.7Syn Z: 0.13

Background carrier burden — how many people carry a rare variant somewhere in PRR27?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

298 rare PASS variants

Rare truncating (LoF)

1 in 2,500

51 rare PASS variants

Rare synonymous (reference)

1 in 400

110 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRR27. 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 250	1 in 3,300
South Asian	~43k	1 in 150	1 in 3,200
Remaining (unassigned)	~30k	1 in 130	1 in 2,300
European (Finnish)	~27k	1 in 240	≈ 1 in 13,000
Admixed American	~22k	1 in 150	1 in 2,000
African / African American	~21k	1 in 240	1 in 410
East Asian	~20k	1 in 140	1 in 1,400
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 260	≈ 1 in 2,900

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 4 coding exons well covered in gnomAD exomes; exons 2, 4 marginal. Genomes: all 4.? see exons ↓