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…

DNmechanismLOEUF 1.64

Clinical Summary— PRR27

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 VUS of 47 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.76top 25%

GOF

0.5367th %ile

LOF

0.2091th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Likely Benign8

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	39	0	39
Likely Benign	3	5	8
Benign	0	0	0
Total	42	5	47

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap PRR27 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →