SPEM2

Chr 17

SPEM family member 2

Also known as: C17orf74

NCBI Gene: 201243ENSG00000184560UniProt: 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
DNmechanismLOEUF 1.37
Clinical Summary— SPEM2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 13 VUS of 41 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
1.37LOEUF
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 OE0.92 (0.64–1.37)
0≤0.351.4
Missense OE1.01 (0.92–1.10)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 18 / 19.5Missense obs/exp: 342 / 338.4Syn Z: 0.92
DN
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.

ClinVar Variant Classifications

41 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS13
24
Pathogenic
3
Likely Pathogenic
13
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
3
0
3
VUS
0
8
5
0
13
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0832040

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

View in ClinVar →

Protein Context — Lollipop Plot

SPEM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients