SV2B

Chr 15

synaptic vesicle glycoprotein 2B

Also known as: HsT19680, SLC22B2

NCBI Gene: 9899 ENSG00000185518 UniProt: Q7L1I2 OMIM: 185861

The protein is a synaptic vesicle membrane protein that regulates vesicle trafficking and exocytosis in neural and endocrine cells. Mutations cause autosomal recessive infantile epileptic encephalopathy, typically with onset in early infancy. The gene is highly constrained against loss-of-function variants (LOEUF 0.63), indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the synaptic vesicle proteins 2 (SV2) family and major facilitator superfamily of proteins. This protein and other members of the family are localized to synaptic vesicles and may function in the regulation of vesicle trafficking and exocytosis. Studies in mice suggest that the encoded protein may act as a protein receptor for botulinum neurotoxin E in neurons, and that this protein may be important for the integrity of the glomerular filtration barrier. This gene shows reduced expression in areas of synaptic loss in the hippocampus of human temporal lobe epilepsy patients. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.000

Z-score 3.20

OE 0.40 (0.26–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.16Z-score

OE missense 0.83 (0.76–0.92)

327 obs / 391.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.26–0.63)

0≤0.351.4

Missense OE?0.83 (0.76–0.92)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 13 / 32.7Missense obs/exp: 327 / 391.7Syn Z: 0.83

Background carrier burden — how many people carry a rare variant somewhere in SV2B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 65

815 rare PASS variants

Rare truncating (LoF)

1 in 3,500

76 rare PASS variants

Rare synonymous (reference)

1 in 100

334 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SV2B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 92	1 in 3,500
South Asian	~43k	1 in 64	1 in 4,300
Remaining (unassigned)	~30k	1 in 57	1 in 2,300
European (Finnish)	~27k	1 in 130	≈ 1 in 13,000
Admixed American	~22k	1 in 81	1 in 2,200
African / African American	~21k	1 in 61	≈ 1 in 4,400
East Asian	~20k	1 in 94	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 300	1 in 1,400
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓