SP140

Chr 2

SP140 nuclear body protein

Also known as: LYSP100, LYSP100-A, LYSP100-B

NCBI Gene: 11262ENSG00000079263UniProt: Q13342

SP140 encodes a nuclear body component that regulates chromatin-mediated gene expression and is highly expressed in leukocyte nuclei. Mutations cause chronic intestinal pseudo-obstruction with myopathy and ophthalmoplegia, following autosomal recessive inheritance. This gene is highly intolerant to loss-of-function variants, suggesting complete loss of function has severe biological consequences.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
55
P/LP submissions
2%
P/LP missense
0.59
LOEUF
DN
Mechanism· predicted
Clinical Summary— SP140
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 unique Pathogenic / Likely Pathogenic· 235 VUS of 490 total submissions
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GeneReview available — SP140
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 4.00
OE 0.41 (0.29–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.79Z-score
OE missense 0.90 (0.82–0.97)
407 obs / 454.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.29–0.59)
0≤0.351.4
Missense OE0.90 (0.82–0.97)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 22 / 53.6Missense obs/exp: 407 / 454.2Syn Z: 1.12
DN
0.6551th %ile
GOF
0.5954th %ile
LOF
0.1895th %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

490 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic5
VUS235
Likely Benign131
Benign23
Conflicting9
43
Pathogenic
5
Likely Pathogenic
235
VUS
131
Likely Benign
23
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
33
0
43
Likely Pathogenic
2
0
3
0
5
VUS
1
218
14
2
235
Likely Benign
0
19
51
61
131
Benign
0
8
9
6
23
Conflicting
—9
Total1224611069446

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

View in ClinVar →

Protein Context — Lollipop Plot

SP140 · 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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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