GOSR2

Chr 17AR

golgi SNAP receptor complex member 2

Also known as: Bos1, EPM6, GS27, MYOS

NCBI Gene: 9570 ENSG00000108433 UniProt: O14653 OMIM: 604027

This gene encodes a trafficking membrane protein that transports proteins from the cis/medial-Golgi to the trans-Golgi network. Biallelic mutations cause autosomal recessive progressive myoclonic epilepsy type 6 and congenital muscular dystrophy with or without seizures. The gene shows low constraint to loss-of-function variation (pLI near zero), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.352 OMIM phenotypes

Clinical Summary— GOSR2

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Gene-Disease Validity (ClinGen)

progressive myoclonus epilepsy · 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

29 unique Pathogenic / Likely Pathogenic· 157 VUS of 349 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GOSR2

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?

1.35LOEUF

pLI 0.000

Z-score 0.63

OE 0.81 (0.51–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.49Z-score

OE missense 1.12 (0.98–1.29)

138 obs / 122.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.81 (0.51–1.35)

0≤0.351.4

Missense OE?1.12 (0.98–1.29)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 11 / 13.5Missense obs/exp: 138 / 122.8Syn Z: -0.15

This gene — mechanism propensity

0.82top 10%

GOF

0.6540th %ile

LOF

0.2288th %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

349 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic10

VUS157

Likely Benign103

Benign34

Conflicting17

Pathogenic

Likely Pathogenic

157

VUS

103

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	3	2	0	19
Likely Pathogenic	8	2	0	0	10
VUS	7	133	14	3	157
Likely Benign	0	5	53	45	103
Benign	1	2	29	2	34
Conflicting	—				17
Total	30	145	98	50	340

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap GOSR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →