SPEM2

Chr 17

SPEM family member 2

Also known as: C17orf74

NCBI Gene: 201243 ENSG00000184560 UniProt: Q0P670

The SPEM2 protein is predicted to be located in cellular membranes, though its specific function remains unclear. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in early infancy with severe seizures and neurodevelopmental delays. This gene shows minimal constraint against loss-of-function variants in population databases.

ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.37

Clinical Summary— SPEM2

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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?

1.37LOEUF

pLI 0.000

Z-score 0.32

OE 0.92 (0.64–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.07Z-score

OE missense 1.01 (0.92–1.10)

342 obs / 338.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.92 (0.64–1.37)

0≤0.351.4

Missense OE?1.01 (0.92–1.10)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 18 / 19.5Missense obs/exp: 342 / 338.4Syn Z: 0.92

This gene — mechanism propensity

0.74top 25%

GOF

0.5857th %ile

LOF

0.3356th %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.