SP110

Chr 2AR

SP110 nuclear body protein

Also known as: IFI41, IFI75, IPR1, VODI

NCBI Gene: 3431ENSG00000135899UniProt: Q9HB58

SP110 encodes a transcription factor that functions as a nuclear hormone receptor coactivator and enhances transcription of genes with retinoic acid response elements. Autosomal recessive mutations cause hepatic venoocclusive disease with immunodeficiency and increased susceptibility to mycobacterial infections. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

{Mycobacterium tuberculosis, susceptibility to}MIM #607948
Hepatic venoocclusive disease with immunodeficiencyMIM #235550
AR
1
Active trials
8
Pubs (1 yr)
31
P/LP submissions
0%
P/LP missense
0.94
LOEUF
DN
Mechanism· predicted
Clinical Summary— SP110
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Gene-Disease Validity (ClinGen)
hepatic veno-occlusive disease-immunodeficiency syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 145 VUS of 300 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — SP110
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.83
OE 0.69 (0.51–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.33Z-score
OE missense 0.95 (0.87–1.04)
355 obs / 373.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.51–0.94)
0≤0.351.4
Missense OE0.95 (0.87–1.04)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 28 / 40.6Missense obs/exp: 355 / 373.2Syn Z: -0.12
DN
0.7132th %ile
GOF
0.5759th %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

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic7
VUS145
Likely Benign90
Benign6
Conflicting6
22
Pathogenic
7
Likely Pathogenic
145
VUS
90
Likely Benign
6
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
15
0
22
Likely Pathogenic
4
0
3
0
7
VUS
2
132
10
1
145
Likely Benign
0
3
44
43
90
Benign
0
0
5
1
6
Conflicting
—6
Total131357745276

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

View in ClinVar →

Protein Context — Lollipop Plot

SP110 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Epigenetic regulation of Fructose-1,6-bisphosphatase 1 by host transcription factor Speckled 110 kDa during hepatitis B virus infection.
Sengupta I et al.·FEBS J
2022
Polymorphisms in the ASAP1 and SP110 Genes and Its Association with the Susceptibility to Pulmonary Tuberculosis in a Mongolian Population
Cui X et al.·J Immunol Res
2022
Nucleotide sequence variants, gene expression and serum profile of immune and antioxidant markers associated with brucellosis resistance/susceptibility in Shami goat
Elsayed AA et al.·Ir Vet J
2025
Identification of common diagnostic genes and molecular pathways in endometriosis and systemic lupus erythematosus by machine learning approach and in vitro experiment
Yang P et al.·Int J Med Sci
2025
Uncovering Deletion/Insertion Mutations in Veno-Occlusive Disease with Immunodeficiency Syndrome in An Iranian Family: A Case Report.
Mohammadi P et al.·Cell J
2024Case report
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