BET1

Chr 7AR

Bet1 golgi vesicular membrane trafficking protein

Also known as: HBET1, MDRP

NCBI Gene: 10282 ENSG00000105829 UniProt: O15155 OMIM: 605456

The BET1 protein is required for vesicular transport from the endoplasmic reticulum to the Golgi complex, functioning as a SNARE protein involved in docking ER-derived vesicles with the cis-Golgi membrane. Mutations cause autosomal recessive congenital muscular dystrophy with rapid progression. The gene shows low constraint to loss-of-function variation (pLI 0.004, LOEUF 1.60).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a golgi-associated membrane protein that participates in vesicular transport from the endoplasmic reticulum (ER) to the Golgi complex. The encoded protein functions as a soluble N-ethylaleimide-sensitive factor attachment protein receptor and may be involved in the docking of ER-derived vesicles with the cis-Golgi membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.601 OMIM phenotype

Clinical Summary— BET1

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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

1 unique Pathogenic / Likely Pathogenic· 13 VUS of 19 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.60LOEUF

pLI 0.004

Z-score 0.57

OE 0.74 (0.36–1.60)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.22Z-score

OE missense 0.92 (0.73–1.16)

52 obs / 56.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.36–1.60)

0≤0.351.4

Missense OE?0.92 (0.73–1.16)

0≤0.61.4

Synonymous OE?0.53

0≤1.21.6

LoF obs/exp: 4 / 5.4Missense obs/exp: 52 / 56.6Syn Z: 1.68

This gene — mechanism propensity

0.86top 5%

GOF

0.73top 25%

LOF

0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

19 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS13

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	1	12	13
Likely Benign	0	0	0
Benign	0	0	0
Total	2	12	14

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap BET1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →