RETREG3

Chr 17

reticulophagy regulator family member 3

Also known as: FAM134C

NCBI Gene: 162427UniProt: Q86VR2

Predicted to enable endoplasmic reticulum-autophagosome adaptor activity. Involved in endoplasmic reticulum tubular network organization; positive regulation of neuron projection development; and reticulophagy. Located in endoplasmic reticulum tubular network. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
91
ClinVar variants
7
Pathogenic / LP
0.5
Missense Z
0.52
LOEUF
6
Pubs (2 yr)
Clinical Summary— RETREG3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 75 VUS of 91 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.52LOEUF
pLI 0.130
Z-score 3.28
OE 0.26 (0.14–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.46Z-score
OE missense 0.92 (0.83–1.02)
259 obs / 280.9 exp
Tolerant

Mild missense constraint

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.0.26 (0.14–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.83–1.02)
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.1.02
0≤1.21.6
LoF obs/exp: 6 / 22.9Missense obs/exp: 259 / 280.9Syn Z: -0.20

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS75
Likely Benign3
Benign6
6
Pathogenic
1
Likely Pathogenic
75
VUS
3
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
1
0
0
1
VUS
0
72
3
0
75
Likely Benign
0
1
2
0
3
Benign
0
2
2
2
6
Total07613291

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

View in ClinVar →

Protein Context — Lollipop Plot

RETREG3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
CSNK2/CK2 regulates selective autophagy of the endoplasmic reticulum
Stolz A·Autophagy
2024
Function of CSNK2/CK2 selectively affects the endoplasmic reticulum and the Golgi apparatus in mtor-mediated autophagy induction.
Sanz-Martinez P et al.·Autophagy
2024
Reticulophagy receptor FAM134C restrains BMP receptor signaling
Gu S et al.·EMBO J
2025
Role of FAM134 paralogues in endoplasmic reticulum remodeling, ER-phagy, and Collagen quality control
Reggio A et al.·EMBO Rep
2021Functional
Cargo-interacting regions (CIR) of CCPG1 capture ER luminal cargos for reticulophagy
Chino H et al.·Autophagy Rep
2023
Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy
Di Lorenzo G et al.·Sci Adv
2022
Reticulophagy and viral infection
Wilson A et al.·Autophagy
2024
Organellophagy regulates cell death:A potential therapeutic target for inflammatory diseases
Duan Y et al.·J Adv Res
2024
Fam134c and Fam134b shape axonal endoplasmic reticulum architecture in vivo
Iavarone F et al.·EMBO Rep
2024
Top 9 full-text resultsSearch PubTator3 ↗

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients