PRR7

Chr 5

proline rich 7, synaptic

NCBI Gene: 80758 ENSG00000131188 UniProt: Q8TB68 OMIM: 618306

PRR7 encodes a protein that acts as a synapse-to-nucleus messenger promoting NMDA receptor-mediated excitotoxicity and regulates transcription factor JUN activity by inhibiting its degradation and promoting its phosphorylation. The gene is highly constrained against loss-of-function variants (pLI = 0.87, LOEUF = 0.45), but no specific human disease has been definitively associated with PRR7 mutations to date. Given its role in neuronal excitotoxicity and apoptosis, mutations would likely follow an autosomal inheritance pattern and potentially affect the central nervous system.

OMIM ResearchSummary from RefSeq, UniProt

Enables long-chain fatty acid binding activity; protein tyrosine kinase binding activity; and ubiquitin-like protein ligase binding activity. Involved in positive regulation of apoptotic process and regulation of transcription by RNA polymerase I. Located in several cellular components, including cytosol; nucleoplasm; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM 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

0.45

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.869

Z-score 2.39

OE 0.00 (0.00–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.29Z-score

OE missense 0.69 (0.58–0.82)

93 obs / 135.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.45)

0≤0.351.4

Missense OE?0.69 (0.58–0.82)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 0 / 6.6Missense obs/exp: 93 / 135.4Syn Z: -1.53

Background carrier burden — how many people carry a rare variant somewhere in PRR7?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 400

419 rare PASS variants

Rare truncating (LoF)

1 in 17,000

21 rare PASS variants

Rare synonymous (reference)

1 in 540

237 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRR7. 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 440	1 in 28,000
South Asian	~43k	1 in 570	1 in 2,000
Remaining (unassigned)	~30k	1 in 390	none seen
European (Finnish)	~26k	1 in 410	1 in 4,000
Admixed American	~22k	1 in 310	≈ 1 in 5,700
African / African American	~21k	1 in 210	≈ 1 in 14,000
East Asian	~20k	1 in 280	none seen
Ashkenazi Jewish	~13k	1 in 700	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 460	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): 1 of 2 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 2.? see exons ↓