PRR12

Chr 19AD

proline rich 12

NCBI Gene: 57479ENSG00000126464UniProt: Q9ULL5

May play a role in the regulation of cohesin complex loading onto chromatin, probably acting in coordination with NIPBL and MAU2

Primary Disease Associations & Inheritance

Neuroocular syndromeMIM #619539
AD
574
ClinVar variants
43
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PRR12
🧬
Gene-Disease Validity (ClinGen)
neuroocular syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 354 VUS of 574 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.05LOEUF
pLI 1.000
Z-score 7.04
OE 0.00 (0.00–0.05)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.98Z-score
OE missense 0.76 (0.72–0.81)
970 obs / 1268.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.05)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.72–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 0 / 57.7Missense obs/exp: 970 / 1268.3Syn Z: -3.29

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic18
VUS354
Likely Benign162
Benign13
Conflicting2
25
Pathogenic
18
Likely Pathogenic
354
VUS
162
Likely Benign
13
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
8
0
25
Likely Pathogenic
11
0
7
0
18
VUS
1
342
11
0
354
Likely Benign
0
91
4
67
162
Benign
0
4
0
9
13
Conflicting
—2
Total294373076574

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

View in ClinVar →

Protein Context — Lollipop Plot

PRR12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PRR12-related intellectual disability and iris abnormalities

strong
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neuroocular syndrome

MIM #619539

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities.
Chowdhury F et al.·Genet Med
2021
Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.
Acosta-Herrera M et al.·Ann Rheum Dis
2019Meta-analysis
Splicing and frameshift variants in QSER1 may be involved in developmental phenotypes.
Fischer MC et al.·HGG Adv
2026
Dominant variants in PRR12 result in unilateral or bilateral complex microphthalmia.
Reis LM et al.·Clin Genet
2021
De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities.
Leduc MS et al.·Hum Genet
2018Cohort
A de novo t(10;19)(q22.3;q13.33) leads to ZMIZ1/PRR12 reciprocal fusion transcripts in a girl with intellectual disability and neuropsychiatric alterations.
Córdova-Fletes C et al.·Neurogenetics
2015
Whole-exome sequencing in three children with sporadic Blau syndrome, one of them co-presenting with recurrent polyserositis.
Córdova-Fletes C et al.·Autoimmunity
2020Case report
Genome-Wide Analysis of Disordered Eating Behavior in the Mexican Population.
Martínez-Magaña JJ et al.·Nutrients
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools