RETREG1

Chr 5AR

reticulophagy regulator 1

Also known as: FAM134B, JK-1, JK1

NCBI Gene: 54463ENSG00000154153UniProt: Q9H6L5OMIM: 613114

The protein is an endoplasmic reticulum-anchored autophagy regulator that mediates ER delivery into lysosomes and is required for long-term survival of nociceptive and autonomic ganglion neurons. Mutations cause hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), which affects sensory and autonomic nervous systems. The inheritance pattern is autosomal recessive.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.861 OMIM phenotype
Clinical Summary— RETREG1
🧬
Gene-Disease Validity (ClinGen)
hereditary sensory and autonomic neuropathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 248 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — RETREG1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.06
OE 0.53 (0.34–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.60Z-score
OE missense 0.89 (0.80–1.00)
214 obs / 240.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.34–0.86)
0≤0.351.4
Missense OE0.89 (0.80–1.00)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 12 / 22.5Missense obs/exp: 214 / 240.1Syn Z: 0.27

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic5
VUS248
Likely Benign158
Benign29
Conflicting6
48
Pathogenic
5
Likely Pathogenic
248
VUS
158
Likely Benign
29
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
32
0
48
Likely Pathogenic
5
0
0
0
5
VUS
5
214
29
0
248
Likely Benign
0
0
64
94
158
Benign
0
0
27
2
29
Conflicting
—6
Total2621415296494

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

View in ClinVar →

Protein Context — Lollipop Plot

RETREG1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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