SP110

Summary

SP110 (SP110 nuclear body protein, HGNC:5401) is a protein-coding gene on chromosome 2q37.1, encoding Sp110 nuclear body protein (Q9HB58). Transcription factor.

The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified.

Source: NCBI Gene 3431 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hepatic veno-occlusive disease-immunodeficiency syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 487 total — 18 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes
• MANE Select transcript: NM_080424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5401
Approved symbol	SP110
Name	SP110 nuclear body protein
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135899
Ensembl biotype	protein_coding
OMIM	604457
Entrez	3431

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 18 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000258381, ENST00000258382, ENST00000358662, ENST00000392048, ENST00000409815, ENST00000455674, ENST00000462232, ENST00000463022, ENST00000477068, ENST00000480916, ENST00000483067, ENST00000486146, ENST00000489597, ENST00000490880, ENST00000540870, ENST00000698099, ENST00000698100, ENST00000698101, ENST00000698102, ENST00000698103, ENST00000698104, ENST00000897325, ENST00000897326, ENST00000897327, ENST00000897328, ENST00000931303, ENST00000948168, ENST00000948169, ENST00000948170

RefSeq mRNA: 10 — MANE Select: NM_080424 NM_001185015, NM_001378442, NM_001378443, NM_001378444, NM_001378445, NM_001378446, NM_001378447, NM_004509, NM_004510, NM_080424

CCDS: CCDS2474, CCDS2475, CCDS2476, CCDS54435

Canonical transcript exons

ENST00000258381 — 19 exons

Exon	Start	End
ENSE00000922484	230172844	230172959
ENSE00000922486	230171696	230171767
ENSE00001921136	230219874	230219984
ENSE00003490143	230172066	230172174
ENSE00003579652	230170621	230170761
ENSE00003620921	230216781	230216928
ENSE00003672553	230165186	230169237
ENSE00003801461	230212347	230212430
ENSE00003801466	230178157	230178255
ENSE00003802753	230207991	230208059
ENSE00003802841	230214950	230215118
ENSE00003803254	230212761	230213027
ENSE00003803775	230177538	230177680
ENSE00003804584	230209931	230210008
ENSE00003806438	230211470	230211553
ENSE00003806765	230200885	230200965
ENSE00003807636	230202579	230202728
ENSE00003807753	230185994	230186143
ENSE00003810795	230183572	230183640

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.7608 / max 1687.7578, expressed in 1754 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34448	33.7711	1744
34447	2.3327	482
34450	0.7121	258
34451	0.7100	201
34449	0.6948	390
34446	0.5401	249

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.73	gold quality
mononuclear cell	CL:0000842	97.64	gold quality
leukocyte	CL:0000738	97.56	gold quality
blood	UBERON:0000178	97.45	gold quality
lymph node	UBERON:0000029	96.03	gold quality
spleen	UBERON:0002106	95.45	gold quality
granulocyte	CL:0000094	95.43	gold quality
vermiform appendix	UBERON:0001154	94.79	gold quality
tendon of biceps brachii	UBERON:0008188	94.51	gold quality
buccal mucosa cell	CL:0002336	93.88	gold quality
sural nerve	UBERON:0015488	93.78	gold quality
caecum	UBERON:0001153	93.76	gold quality
bone marrow cell	CL:0002092	92.95	gold quality
tonsil	UBERON:0002372	92.82	gold quality
gall bladder	UBERON:0002110	92.80	gold quality
calcaneal tendon	UBERON:0003701	92.80	gold quality
tendon	UBERON:0000043	92.73	gold quality
bone marrow	UBERON:0002371	91.76	gold quality
endothelial cell	CL:0000115	91.19	gold quality
pancreatic ductal cell	CL:0002079	90.88	gold quality
bone element	UBERON:0001474	90.47	gold quality
superficial temporal artery	UBERON:0001614	90.43	gold quality
right lung	UBERON:0002167	90.33	gold quality
trabecular bone tissue	UBERON:0002483	90.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.97	gold quality
tibial nerve	UBERON:0001323	89.90	gold quality
upper lobe of left lung	UBERON:0008952	89.76	gold quality
lower lobe of lung	UBERON:0008949	89.71	gold quality
omental fat pad	UBERON:0010414	89.66	gold quality
peritoneum	UBERON:0002358	89.64	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	999.77
E-HCAD-13	yes	22.94
E-ANND-3	yes	22.01
E-HCAD-10	yes	14.92
E-CURD-112	yes	12.67
E-MTAB-9067	yes	12.59
E-MTAB-6911	no	39.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting SP110, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-4280	96.44	67.69	473
HSA-MIR-3935	96.33	66.79	797

Literature-anchored findings (GeneRIF, showing 30)

• data suggest that Sp110b is a transcriptional cofactor negatively regulating retinoic acid receptor alpha-mediated transcription (PMID:14559998)
• Sp110b is a component of the cellular machinery that Epstein-Barr virus utilizes to enhance lytic EBV replication (PMID:15308735)
• reports the involvement of a Sp110 nuclear body protein in a human primary immunodeficiency and high-penetrance genetic mutations in hepatic veno-occlusive disease (PMID:16648851)
• identified three polymorphisms that are associated with disease (PMID:16803959)
• Hypothesis that Sp110 variants and haplotypes might be associated with distinct phenotypes of human M tuberculosis infection is doubtful. (PMID:16816019)
• description of a minor histocompatibility antigen created by a polymorphism in the SP110 gene; the antigenic peptide comprises 2 noncontiguous SP110 peptide segments spliced together in reverse order to that in which they occur in predicted SP110 protein (PMID:16960008)
• common polymorphisms of the SP110 gene have no major effect on susceptibility to tuberculosis in the Russian population (PMID:17149599)
• Our finding suggests that genetic variations in the CYP19A1 gene are significantly associated with BMD at different skeletal sites in adult men, but not in women. (PMID:17287948)
• familial hepatic veno-occlusive disease with immunodeficiency due to a homozygous truncating mutation in exon 5; SP110 c.642delC (PMID:17510920)
• Sp110 expression is required for Anaplasma phagocytophilum infection and multiplication in human promyelocytic cells. A.phagocytophilum may modulate Sp110 mRNA levels to facilitate establishment of infection of human HL-60 cells. (PMID:17883869)
• Several SNPs in Sp110 are risk factors for susceptibility to tuberculosis in Chongqing Han People. (PMID:21033425)
• identification of two proteins: the human remodeling and spacing factor 1 (RSF1) and the activating transcription factor 7 interacting protein (ATF7IP) that interact with human SP110 during the process of viral infections (PMID:21222611)
• This study demonstrates that genotypes and haplotypes of SP110 might be associated with susceptibility to tuberculosis in Chinese population. (PMID:21397050)
• the results might indicate a role of SP110 variants in extrapulmonary tuberculosis rather than PTB. (PMID:21536091)
• Genotyped 20 SNPs located in the SP110 gene, for the first time in a South East Asian cohort from Indonesia.Our study did not reveal any statistically significant associations between SP110 SNPs and pulmonary TB. (PMID:22522001)
• a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause veno-occlusive disease with immunodeficiency syndrome. (PMID:22621957)
• In a pooled analysis of 10,624 cases of tuberculosis, there was not a significant association between polymorphisms in the SP110 gene and disease susceptibility. [Meta-analysis] (PMID:22691368)
• Study suggests that a combination of SP110 and MYBBP1A gene polymorphisms may serve as a novel marker for identifying the risk of developing TB in the Chinese Han population. (PMID:23129390)
• Results show that SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary tuberculosis in the Vietnamese patients. Those variants may influence macrophage signaling responses and apoptosis during the infection. (PMID:25006821)
• The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 in MYBBP1A had significant effects on the risk of pulmonary tuberculosis, and heterozygous genotype CT in rs9061 in SP110 also had similar effects. (PMID:25612917)
• SP110 polymorphism is associated with tuberculosis. (PMID:27623071)
• Using mouse models and genetic characteristics of human patients the role of SP110b was studied to determine its role in controlling host immunity and susceptibility to TB by modulating nuclear factor-kappaB (NF-kappaB) activity resulting in down regulation of TNF-alpha production and upregulation of NF-kappaB-induced antipoptotic gene expression suppressing IFN-gamma-mediated monocyte and/or macrophage cell death. (PMID:27858493)
• Data suggest that Sp110 is sumoylated, de-sumoylated, and then released from the promyelocytic leukemia nuclear bodies in hepatocytes infected with HBV (hepatitis B virus); Sp110 differentially regulates several direct target genes of HBx, a viral co-factor; these mechanisms may be involved in evasion of host immune response by HBV. (Sp110 = Speckled 110 kDa; HBx = hepatitis B virus protein X) (PMID:29046350)
• TNF-alpha -308G>A (rs1800629) showed no association with susceptibility to pulmonary tuberculosis and spinal tuberculosis patients in southern China. (PMID:29430075)
• Results suggest that the SP110 variants have a role in controlling genetic susceptibility to latent and active tuberculosis (TB) infection in Taiwan. Additionally, the SP110 rs9061 SNP is shown to be associated with plasma TNFalpha levels in LTBI individuals. These data suggest that the identified SP110 SNPs may serve as a biomarker for latent and active TB infection in Taiwan. (PMID:30627224)
• Novel Missense Mutation inSP110Associated with Combined Immunodeficiency and Advanced Liver Disease Without VOD. (PMID:31721003)
• HSP60, SP110 and TNF-alpha expression in Chlamydia pneumoniae-positive versus Chlamydia pneumoniae-negative atherosclerotic plaques. (PMID:35308005)
• Epigenetic regulation of Fructose-1,6-bisphosphatase 1 by host transcription factor Speckled 110 kDa during hepatitis B virus infection. (PMID:35653238)
• Polymorphisms in the ASAP1 and SP110 Genes and Its Association with the Susceptibility to Pulmonary Tuberculosis in a Mongolian Population. (PMID:36249417)
• Transcriptional regulators SP110 and SP140 modulate inflammatory response genes in Mycobacterium tuberculosis-infected human macrophages. (PMID:39162523)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sp110	ENSMUSG00000070034
		ENSMUSG00000079808
		ENSMUSG00000094799
		ENSMUSG00000094874
		ENSMUSG00000095092
		ENSMUSG00000095250
		ENSMUSG00000095672
rattus_norvegicus	Sp110	ENSRNOG00000033747
caenorhabditis_elegans	hmg-3	WBGENE00001973
caenorhabditis_elegans		WBGENE00001974

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), UBTF (ENSG00000108312), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

Sp110 nuclear body protein — Q9HB58 (reviewed: Q9HB58)

Alternative names: Interferon-induced protein 41/75, Speckled 110 kDa, Transcriptional coactivator Sp110

All UniProt accessions (8): A0A8V8TLE9, A0A8V8TLH4, Q9HB58, A0A8V8TMX7, A0A8V8TN67, C9JZQ4, E7EM70, G5E9C0

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. May be a nuclear hormone receptor coactivator. Enhances transcription of genes with retinoic acid response elements (RARE).

Subunit / interactions. (Microbial infection) Isoform 3 interacts with HCV core protein.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in peripheral blood leukocytes and spleen. Detected at intermediate levels in thymus, prostate, testis, ovary, small intestine and colon, and at low levels in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Phosphorylated (isoform 2).

Disease relevance. Hepatic venoocclusive disease with immunodeficiency (VODI) [MIM:235550] Autosomal recessive primary immunodeficiency associated with hepatic vascular occlusion and fibrosis. The immunodeficiency is characterized by severe hypogammaglobulinemia, combined T and B-cell immunodeficiency, absent lymph node germinal centers, and absent tissue plasma cells. The disease is caused by variants affecting the gene represented in this entry.

Induction. By IFNG/IFN-gamma and all-trans retinoic acid (ATRA).

Isoforms (7)

UniProt ID	Names	Canonical?
Q9HB58-1	1	yes
Q9HB58-2	2, IFI75, 75
Q9HB58-3	3, Sp110b
Q9HB58-4	4, IFI41, 41
Q9HB58-5	5
Q9HB58-6	6
Q9HB58-7	7

RefSeq proteins (10): NP_001171944, NP_001365371, NP_001365372, NP_001365373, NP_001365374, NP_001365375, NP_001365376, NP_004500, NP_004501, NP_536349* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000770	SAND_dom	Domain
IPR001487	Bromodomain	Domain
IPR001965	Znf_PHD	Domain
IPR004865	HSR_dom	Domain
IPR010919	SAND-like_dom_sf	Homologous_superfamily
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR043563	Sp110/Sp140/Sp140L-like	Family

Pfam: PF01342, PF03172

UniProt features (51 total): sequence variant 16, splice variant 11, compositionally biased region 6, modified residue 5, domain 3, sequence conflict 3, region of interest 3, short sequence motif 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HB58-F1	58.63	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 175, 177, 244, 256, 380

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 396 (showing top): MODULE_45, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, RIZKI_TUMOR_INVASIVENESS_3D_DN, GNF2_LYN, WIELAND_UP_BY_HBV_INFECTION, SMITH_TERT_TARGETS_DN, IRF7_01, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, ONKEN_UVEAL_MELANOMA_UP, FOSTER_TOLERANT_MACROPHAGE_UP, MARTINEZ_RB1_TARGETS_DN

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), defense response (GO:0006952)

GO Molecular Function (5): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), nuclear lumen (GO:0031981)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
response to stress	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SP110	SLC11A1	P49279	627
SP110	KBTBD3	Q8NAB2	526
SP110	IL12B	P29460	497
SP110	MRC1	P22897	497
SP110	LTA4H	P09960	494
SP110	IRGM	A1A4Y4	492
SP110	SFTPA2	P07714	468
SP110	IFNGR2	P38484	466
SP110	IL12RB1	P42701	451
SP110	NOS2	P35228	439
SP110	NUCLEOLIN	P19338	424
SP110	CD209	Q9NNX6	423
SP110	TIRAP	P58753	420
SP110	EIF2AK2	P19525	397
SP110	AEBP1	Q8IUX7	396

IntAct

16 interactions, top by confidence:

A	B	Type	Score
RUNX3	SP110	psi-mi:“MI:0915”(physical association)	0.370
SP110	NAP1L2	psi-mi:“MI:0915”(physical association)	0.370
SP110	ZSCAN9	psi-mi:“MI:0915”(physical association)	0.370
SP110	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
CDKN1A	SP110	psi-mi:“MI:0915”(physical association)	0.370
OSGEP	SP110	psi-mi:“MI:0915”(physical association)	0.370
SMN1	SP110	psi-mi:“MI:0915”(physical association)	0.370
SP110	TK1	psi-mi:“MI:0915”(physical association)	0.370
SP110	TSC22D1	psi-mi:“MI:0915”(physical association)	0.370
TTR	SP110	psi-mi:“MI:0915”(physical association)	0.370
SP110	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
ZNF800	MED19	psi-mi:“MI:2364”(proximity)	0.270
SP110		psi-mi:“MI:0915”(physical association)	0.000
NDUFV2	SP110	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (139): SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Affinity Capture-MS), SP110 (Proximity Label-MS), SP110 (Affinity Capture-RNA), SP110 (Affinity Capture-MS), SP110 (Two-hybrid)

ESM2 similar proteins: A0A0J9YX57, A1A5P9, A2A368, A2A9R3, A8MXT2, B2KFW1, O15479, O15480, O15481, O15553, P0C6Y7, P10073, P17040, P25233, P43355, P43356, P43357, P43358, P43360, P43362, P43363, P43364, P43366, Q13342, Q16666, Q4R998, Q5PPP4, Q5RD14, Q6AY37, Q6PCZ4, Q8BQR7, Q8IWY8, Q8IX06, Q8N660, Q8N7X4, Q8TD90, Q96DU7, Q96LZ2, Q96M61, Q99608

Diamond homologs: A0A7U2QYM2, A2A8L1, A2BIL7, B2RWS6, D3ZD32, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F4IXE7, F4KBP5, F7DRV9, G5EBZ4, O15016, O16102, O43918, O60885, O74964, O88379, O88491, O96028, O97159, P13709, P25440, P35817, P45481, Q07442, Q08D75, Q09472, Q12830, Q12873, Q13342, Q14839, Q15059, Q22516, Q32S26, Q338B9, Q4R8Y1, Q54UW4, Q58F21

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

487 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	13
Uncertain significance	230
Likely benign	149
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069349	NC_000002.11:g.(?231033820)(231086456_?)del	Pathogenic
1390383	NM_080424.4(SP110):c.436C>T (p.Gln146Ter)	Pathogenic
1451662	NM_080424.4(SP110):c.1933del (p.Leu645fs)	Pathogenic
1458064	NM_080424.4(SP110):c.1775_1778del (p.Val591_Ser592insTer)	Pathogenic
1460016	NC_000002.11:g.(?231042234)(231042416_?)del	Pathogenic
1912459	NM_080424.4(SP110):c.886del (p.Ser296fs)	Pathogenic
2024159	NM_080424.4(SP110):c.463A>T (p.Arg155Ter)	Pathogenic
2155154	NM_080424.4(SP110):c.1067C>A (p.Ser356Ter)	Pathogenic
2416113	NM_080424.4(SP110):c.1631dup (p.Gln545fs)	Pathogenic
2425135	NC_000002.11:g.(?231033840)(231081642_?)del	Pathogenic
2897348	NM_080424.4(SP110):c.943del (p.Val315fs)	Pathogenic
3247280	NC_000002.11:g.(?231065581)(231081642_?)del	Pathogenic
4714257	NM_080424.4(SP110):c.1493_1494insCAAC (p.Pro499fs)	Pathogenic
4721716	NM_080424.4(SP110):c.1359_1360del (p.Lys453_Ser454insTer)	Pathogenic
5538	NM_080424.4(SP110):c.40del (p.Gln14fs)	Pathogenic
574936	NM_080424.4(SP110):c.1395dup (p.Val466fs)	Pathogenic
832842	NC_000002.12:g.(?230176645)(230177700_?)del	Pathogenic
971546	NM_080424.4(SP110):c.1691del (p.Pro564fs)	Pathogenic
1696250	NC_000002.11:g.(231037676_231042253)_(231042397_231042872)del	Likely pathogenic
189244	NM_080424.4(SP110):c.877A>T (p.Lys293Ter)	Likely pathogenic
2433685	NM_080424.4(SP110):c.1766_1767del (p.His589fs)	Likely pathogenic
2800835	NM_080424.4(SP110):c.1130-1G>C	Likely pathogenic
2852086	NM_080424.4(SP110):c.1888-2A>G	Likely pathogenic
2982529	NM_080424.4(SP110):c.1349-2A>T	Likely pathogenic
3064712	NM_080424.4(SP110):c.1816-1G>C	Likely pathogenic
3341350	NM_080424.4(SP110):c.1816-2A>T	Likely pathogenic
3586160	NM_080424.4(SP110):c.1706+2T>G	Likely pathogenic
3666632	NM_080424.4(SP110):c.1447+1G>A	Likely pathogenic
4691593	NM_080424.4(SP110):c.1279+1G>T	Likely pathogenic
4766242	NM_080424.4(SP110):c.1448-2A>G	Likely pathogenic

SpliceAI

2518 predictions. Top by Δscore:

Variant	Effect	Δscore
2:230169235:AGC:A	acceptor_gain	1.0000
2:230169235:AGCC:A	acceptor_loss	1.0000
2:230169236:GC:G	acceptor_gain	1.0000
2:230169236:GCC:G	acceptor_loss	1.0000
2:230169237:CC:C	acceptor_gain	1.0000
2:230169237:CCT:C	acceptor_loss	1.0000
2:230170763:T:C	acceptor_gain	1.0000
2:230209928:TACC:T	donor_loss	1.0000
2:230209929:A:AC	donor_gain	1.0000
2:230209929:ACCTT:A	donor_loss	1.0000
2:230209930:C:CC	donor_gain	1.0000
2:230209930:CCTTT:C	donor_gain	1.0000
2:230210007:CT:C	acceptor_gain	1.0000
2:230210008:TCTGA:T	acceptor_loss	1.0000
2:230210009:C:CC	acceptor_gain	1.0000
2:230211554:C:CC	acceptor_gain	1.0000
2:230212429:CA:C	acceptor_gain	1.0000
2:230212431:C:CC	acceptor_gain	1.0000
2:230214947:TACCA:T	donor_loss	1.0000
2:230214948:A:C	donor_loss	1.0000
2:230214949:C:A	donor_loss	1.0000
2:230214949:CCA:C	donor_gain	1.0000
2:230216925:CATC:C	acceptor_gain	1.0000
2:230216927:TC:T	acceptor_gain	1.0000
2:230216927:TCC:T	acceptor_loss	1.0000
2:230216928:CC:C	acceptor_gain	1.0000
2:230216929:C:CA	acceptor_loss	1.0000
2:230216929:C:CC	acceptor_gain	1.0000
2:230216930:T:C	acceptor_loss	1.0000
2:230217972:A:C	donor_gain	1.0000

AlphaMissense

4716 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:230177622:A:C	F502L	0.987
2:230177622:A:T	F502L	0.987
2:230177624:A:G	F502L	0.987
2:230215011:G:C	F85L	0.985
2:230215011:G:T	F85L	0.985
2:230215013:A:G	F85L	0.985
2:230216835:A:C	F31L	0.981
2:230216835:A:T	F31L	0.981
2:230216837:A:G	F31L	0.981
2:230215038:A:C	F76L	0.979
2:230215038:A:T	F76L	0.979
2:230215040:A:G	F76L	0.979
2:230214957:G:C	F103L	0.978
2:230214957:G:T	F103L	0.978
2:230214959:A:G	F103L	0.978
2:230216818:A:G	L37P	0.977
2:230215060:A:G	L69P	0.973
2:230216848:A:T	I27K	0.973
2:230177623:A:G	F502S	0.971
2:230214958:A:G	F103S	0.971
2:230215012:A:G	F85S	0.971
2:230216830:A:G	F33S	0.971
2:230216881:A:G	F16S	0.971
2:230172882:G:C	F556L	0.970
2:230172882:G:T	F556L	0.970
2:230172884:A:G	F556L	0.970
2:230214999:G:C	N89K	0.970
2:230214999:G:T	N89K	0.970
2:230177662:A:G	I489T	0.969
2:230178180:A:G	L475S	0.969

dbSNP variants (sampled 300 via entrez): RS1000008767 (2:230223532 T>A,C), RS1000078540 (2:230224325 G>A,T), RS1000106186 (2:230165827 C>T), RS1000115344 (2:230178461 C>A), RS1000152382 (2:230172564 C>G,T), RS1000201797 (2:230226179 G>T), RS1000206644 (2:230198247 C>A), RS1000237990 (2:230219228 AAAC>A), RS1000299830 (2:230198564 C>T), RS1000325234 (2:230193197 G>C), RS1000358789 (2:230212730 A>C,G), RS1000426200 (2:230219938 T>C), RS1000450181 (2:230173243 A>G), RS1000513948 (2:230218939 A>C), RS1000534977 (2:230205395 C>T)

Disease associations

OMIM: gene MIM:604457 | disease phenotypes: MIM:235550

GenCC curated gene-disease

Disease	Classification	Inheritance
hepatic veno-occlusive disease-immunodeficiency syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hepatic veno-occlusive disease-immunodeficiency syndrome	Definitive	AR

Mondo (1): hepatic veno-occlusive disease-immunodeficiency syndrome (MONDO:0009338)

Orphanet (1): Hepatic veno-occlusive disease-immunodeficiency syndrome (Orphanet:79124)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000016	Urinary retention
HP:0000252	Microcephaly
HP:0000952	Jaundice
HP:0001269	Hemiparesis
HP:0001392	Abnormality of the liver
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001531	Failure to thrive in infancy
HP:0001541	Ascites
HP:0001873	Thrombocytopenia
HP:0001876	Pancytopenia
HP:0001903	Anemia
HP:0002014	Diarrhea
HP:0002069	Bilateral tonic-clonic seizure
HP:0002100	Recurrent aspiration pneumonia
HP:0002205	Recurrent respiratory infections
HP:0002206	Pulmonary fibrosis
HP:0002240	Hepatomegaly
HP:0002385	Paraparesis
HP:0002415	Leukodystrophy
HP:0002721	Immunodeficiency
HP:0002722	Recurrent abscess formation
HP:0002728	Chronic mucocutaneous candidiasis
HP:0002743	Recurrent enteroviral infections
HP:0002849	Absence of lymph node germinal center
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003139	Panhypogammaglobulinemia
HP:0004315	Decreased circulating IgG concentration
HP:0004429	Recurrent viral infections

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537257	Hepatic venoocclusive disease with immunodeficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066231 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Non-enzymatic BRD containing proteins

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
trichostatin A	increases expression	1
aflatoxin B2	decreases methylation	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Decitabine	increases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	decreases response to substance	1
Daunorubicin	affects response to substance	1
Diethylhexyl Phthalate	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5696887	Binding	Inhibition of SP110 in human HL-60 cells assessed as fold change at 5 uM in presence of biotinylated histone peptide by LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2Q8	Abcam A-549 SP110 KO	Cancer cell line	Male
CVCL_TQ07	HAP1 SP110 (-) 1	Cancer cell line	Male
CVCL_TQ08	HAP1 SP110 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.