RETREG1

Chr 5AR

reticulophagy regulator 1

Also known as: FAM134B, JK-1, JK1

NCBI Gene: 54463 ENSG00000154153 UniProt: Q9H6L5 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a cis-Golgi transmembrane protein that may be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Mutations in this gene are a cause of hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), and this gene may also play a role in susceptibility to vascular dementia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.861 OMIM phenotype

Clinical Summary— RETREG1

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Gene-Disease Validity (ClinGen)

hereditary sensory and autonomic neuropathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

26 unique Pathogenic / Likely Pathogenic· 276 VUS of 535 total submissions

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GeneReview available — RETREG1

Authoritative clinical overview · Recommended first read

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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 OE?0.53 (0.34–0.86)

0≤0.351.4

Missense OE?0.89 (0.80–1.00)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 12 / 22.5Missense obs/exp: 214 / 240.1Syn Z: 0.27

ClinVar Variant Classifications

535 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic5

VUS276

Likely Benign173

Benign39

Conflicting15

Pathogenic

Likely Pathogenic

276

VUS

173

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	0	1	0	21
Likely Pathogenic	5	0	0	0	5
VUS	5	241	29	1	276
Likely Benign	0	3	71	99	173
Benign	0	1	34	4	39
Conflicting	—				15
Total	30	245	135	104	529

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

View in ClinVar →

79 pathogenic / likely-pathogenic (of 89) ClinVar copy-number / structural variants overlap RETREG1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →