SEC22A

Chr 3

SEC22 homolog A, vesicle trafficking protein

Also known as: SEC22L2

NCBI Gene: 26984 ENSG00000121542 UniProt: Q96IW7 OMIM: 612442

SEC22A encodes a vesicle trafficking protein involved in transport between the endoplasmic reticulum and Golgi complex. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and brain malformations. The gene shows minimal constraint against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the member of the SEC22 family of vesicle trafficking proteins. This protein has similarity to rat SEC22 and may act in the early stages of the secretory pathway. [provided by RefSeq, Nov 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.20

Clinical Summary— SEC22A

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.000

Z-score 1.01

OE 0.72 (0.45–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.08Z-score

OE missense 0.98 (0.86–1.12)

161 obs / 163.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.45–1.20)

0≤0.351.4

Missense OE?0.98 (0.86–1.12)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 15.2Missense obs/exp: 161 / 163.8Syn Z: 0.52

This gene — mechanism propensity

0.6743th %ile

GOF

0.5955th %ile

LOF

0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.