SP140L

Summary

SP140L (SP140 like nuclear body protein, HGNC:25105) is a protein-coding gene on chromosome 2q37.1, encoding Nuclear body protein SP140-like protein (Q9H930).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 93349 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 127 total
• Druggable target: yes
• MANE Select transcript: NM_138402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25105
Approved symbol	SP140L
Name	SP140 like nuclear body protein
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185404
Ensembl biotype	protein_coding
OMIM	617747
Entrez	93349

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 5 retained_intron

ENST00000243810, ENST00000396563, ENST00000415673, ENST00000444636, ENST00000458341, ENST00000462156, ENST00000466656, ENST00000483728, ENST00000496870, ENST00000497212, ENST00000909865, ENST00000909866, ENST00000909867, ENST00000909868, ENST00000909869, ENST00000909870, ENST00000909871, ENST00000909872, ENST00000909873, ENST00000955822, ENST00000955823, ENST00000955824

RefSeq mRNA: 6 — MANE Select: NM_138402 NM_001308162, NM_001308163, NM_001352892, NM_001352893, NM_001352894, NM_138402

CCDS: CCDS46538, CCDS77536, CCDS77537

Canonical transcript exons

ENST00000415673 — 19 exons

Exon	Start	End
ENSE00000965539	230361614	230361697
ENSE00001342482	230370908	230370967
ENSE00001766396	230402798	230403732
ENSE00002432872	230401366	230401443
ENSE00002496600	230400955	230401063
ENSE00002505069	230328757	230328831
ENSE00002507201	230358964	230359132
ENSE00003474582	230392087	230392229
ENSE00003564781	230396757	230396798
ENSE00003568115	230388559	230388633
ENSE00003591195	230385224	230385304
ENSE00003616453	230400127	230400242
ENSE00003617548	230393414	230393461
ENSE00003624764	230383510	230383575
ENSE00003625944	230371598	230371651
ENSE00003644214	230389919	230390023
ENSE00003654119	230401664	230401807
ENSE00003660332	230357805	230357967
ENSE00003905746	230327193	230327301

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 94.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.0890 / max 144.4441, expressed in 1518 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25813	9.4965	1513
25814	0.5925	303

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	94.36	gold quality
spleen	UBERON:0002106	93.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.36	gold quality
lymph node	UBERON:0000029	92.24	gold quality
vermiform appendix	UBERON:0001154	92.13	gold quality
monocyte	CL:0000576	92.09	gold quality
mononuclear cell	CL:0000842	91.82	gold quality
leukocyte	CL:0000738	91.72	gold quality
buccal mucosa cell	CL:0002336	91.47	gold quality
rectum	UBERON:0001052	90.77	gold quality
blood	UBERON:0000178	90.06	gold quality
gall bladder	UBERON:0002110	90.00	gold quality
upper lobe of left lung	UBERON:0008952	89.73	gold quality
right lobe of liver	UBERON:0001114	89.64	gold quality
small intestine	UBERON:0002108	89.54	gold quality
right lung	UBERON:0002167	89.31	gold quality
sural nerve	UBERON:0015488	89.11	gold quality
right uterine tube	UBERON:0001302	88.89	gold quality
right adrenal gland	UBERON:0001233	88.83	gold quality
upper lobe of lung	UBERON:0008948	88.72	gold quality
right ovary	UBERON:0002118	88.63	gold quality
right adrenal gland cortex	UBERON:0035827	88.51	gold quality
minor salivary gland	UBERON:0001830	88.26	gold quality
left ovary	UBERON:0002119	88.24	gold quality
left adrenal gland	UBERON:0001234	88.17	gold quality
adrenal tissue	UBERON:0018303	87.83	gold quality
tibial nerve	UBERON:0001323	87.52	gold quality
tonsil	UBERON:0002372	87.50	gold quality
left adrenal gland cortex	UBERON:0035825	87.47	gold quality
transverse colon	UBERON:0001157	87.19	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	34.41
E-ANND-3	yes	12.71
E-MTAB-6386	no	363.30
E-GEOD-124858	no	136.35

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2540.1	SP140L	Sp140-Sp100

JASPAR matrix evidence (PMIDs): PMID:39605320

miRNA regulators (miRDB)

44 targeting SP140L, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-7977	98.65	66.18	2590

Literature-anchored findings (GeneRIF, showing 1)

• our results show that SP140L is phylogenetically recent member of SP100 proteins and acts as an autoantigen in primary biliary cirrhosis patients. (PMID:26347895)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubtf	ENSDARG00000035066
danio_rerio	ubtfl	ENSDARG00000038780
rattus_norvegicus		ENSRNOG00000082639
drosophila_melanogaster	HmgD	FBGN0004362
drosophila_melanogaster	HmgZ	FBGN0010228
drosophila_melanogaster	Ssrp	FBGN0010278
drosophila_melanogaster	CG4617	FBGN0029936
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), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

Nuclear body protein SP140-like protein — Q9H930 (reviewed: Q9H930)

All UniProt accessions (3): Q9H930, H7BYP4, U5Y3L1

UniProt curated annotations — full annotation on UniProt →

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H930-4	4	yes
Q9H930-1	1
Q9H930-2	2
Q9H930-3	3

RefSeq proteins (6): NP_001295091, NP_001295092, NP_001339821, NP_001339822, NP_001339823, NP_612411* (*=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
IPR030411	Sp140_Bromo	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR043563	Sp110/Sp140/Sp140L-like	Family

Pfam: PF00439, PF00628, PF01342, PF03172

UniProt features (22 total): splice variant 5, compositionally biased region 4, domain 3, sequence variant 3, cross-link 2, chain 1, modified residue 1, sequence conflict 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H930-F1	68.47	0.31

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 (3): 180, 169, 292

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MODULE_255, GOZGIT_ESR1_TARGETS_DN, MODULE_317, KOYAMA_SEMA3B_TARGETS_UP, AGCTCCT_MIR28, MODULE_69, GOCC_NUCLEOLUS, RUTELLA_RESPONSE_TO_HGF_UP, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_UP, MODULE_37, DCA_UP.V1_DN, SIRNA_EIF4GI_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR3942_3P

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 (4): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), nuclear lumen (GO:0031981)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SP140L	BRDT	Q58F21	555
SP140L	PML	P29590	529
SP140L	SUMO1	P55856	510
SP140L	SUMO2	P55855	501
SP140L	ATRX	P46100	469
SP140L	BRWD1	Q9NSI6	438
SP140L	BRWD3	Q6RI45	421
SP140L	ZMYND8	Q9ULU4	420
SP140L	ZMYND11	Q15326	403
SP140L	ZNF266	Q14584	391
SP140L	SP140	Q13342	388
SP140L	TAF1L	Q8IZX4	382
SP140L	ATAD2B	Q9ULI0	376
SP140L	CECR2	Q9BXF3	373
SP140L	BRPF3	Q9ULD4	372

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CHCHD2	ZNF593	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Affinity Capture-MS), SP140L (Protein-peptide), SP140L (Reconstituted Complex), APP (Reconstituted Complex)

ESM2 similar proteins: A0A494C1R9, A2AKB4, A2APT9, A6NKD2, A8MT33, B0BN44, E9PGG2, F5GYI3, O19110, O88852, P0CV98, P0CV99, P0CW00, P0CW01, Q01534, Q03386, Q0P5N2, Q12967, Q14684, Q2M329, Q3U3N0, Q5F267, Q5I0E2, Q5R5G8, Q5R866, Q5SYB0, Q5VTJ3, Q60953, Q69ZB3, Q6ZUX3, Q7TQI8, Q80VJ8, Q80VR2, Q86VY4, Q8BSI6, Q8IZJ4, Q8N831, Q8VD63, Q95LS7, Q96FG2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3035 predictions. Top by Δscore:

Variant	Effect	Δscore
2:230357803:A:AG	acceptor_gain	1.0000
2:230357804:G:GG	acceptor_gain	1.0000
2:230357804:GGCT:G	acceptor_gain	1.0000
2:230357962:TTTG:T	donor_gain	1.0000
2:230357965:GAA:G	donor_gain	1.0000
2:230357965:GAAGT:G	donor_loss	1.0000
2:230357966:AA:A	donor_gain	1.0000
2:230357967:AG:A	donor_loss	1.0000
2:230357968:G:GG	donor_gain	1.0000
2:230357968:GTA:G	donor_loss	1.0000
2:230357969:T:A	donor_loss	1.0000
2:230358951:A:AG	acceptor_gain	1.0000
2:230358952:A:G	acceptor_gain	1.0000
2:230358960:AAAG:A	acceptor_gain	1.0000
2:230359090:GAA:G	donor_gain	1.0000
2:230359091:A:T	donor_gain	1.0000
2:230371596:A:AG	acceptor_gain	1.0000
2:230371597:G:GG	acceptor_gain	1.0000
2:230371649:G:GT	donor_gain	1.0000
2:230371649:GAA:G	donor_gain	1.0000
2:230371652:G:GG	donor_gain	1.0000
2:230383500:T:TA	acceptor_gain	1.0000
2:230383508:A:AC	acceptor_loss	1.0000
2:230385222:A:AG	acceptor_gain	1.0000
2:230385223:G:GG	acceptor_gain	1.0000
2:230385302:GGG:G	donor_gain	1.0000
2:230385303:GG:G	donor_gain	1.0000
2:230385303:GGG:G	donor_gain	1.0000
2:230385304:GG:G	donor_gain	1.0000
2:230385304:GGTA:G	donor_loss	1.0000

AlphaMissense

3891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:230401781:T:C	F540L	0.993
2:230401783:C:A	F540L	0.993
2:230401783:C:G	F540L	0.993
2:230357896:G:C	A67P	0.992
2:230392179:T:A	W353R	0.992
2:230392179:T:C	W353R	0.992
2:230400202:T:C	F425L	0.992
2:230400204:C:A	F425L	0.992
2:230400204:C:G	F425L	0.992
2:230401704:T:C	L514S	0.992
2:230359103:T:C	L137S	0.991
2:230392143:T:C	F341L	0.991
2:230392145:T:A	F341L	0.991
2:230392145:T:G	F341L	0.991
2:230400145:T:C	C406R	0.991
2:230359022:T:C	L110P	0.990
2:230400145:T:A	C406S	0.990
2:230400146:G:C	C406S	0.990
2:230401417:T:C	F492L	0.990
2:230401419:T:A	F492L	0.990
2:230401419:T:G	F492L	0.990
2:230357930:T:C	L78P	0.989
2:230400154:T:A	C409S	0.989
2:230400155:G:C	C409S	0.989
2:230401758:T:C	F532S	0.989
2:230357918:T:C	F74S	0.988
2:230400214:T:C	C429R	0.988
2:230401773:G:C	R537P	0.988
2:230357933:G:C	R79P	0.987
2:230402840:T:C	F563L	0.987

dbSNP variants (sampled 300 via entrez): RS1000015595 (2:230358164 A>G), RS1000089777 (2:230327969 A>G), RS1000141924 (2:230383327 G>A,C,T), RS1000155154 (2:230347452 A>C,G), RS1000191555 (2:230342515 G>A,C,T), RS1000213520 (2:230359890 A>C), RS1000224174 (2:230352753 T>C), RS1000257108 (2:230366966 A>C,G), RS1000297950 (2:230352453 A>C,T), RS1000316278 (2:230366760 G>T), RS1000347909 (2:230332965 C>T), RS1000387707 (2:230346174 T>G), RS1000412422 (2:230387711 T>C,G), RS1000421757 (2:230385007 G>A), RS1000476232 (2:230358478 G>T)

Disease associations

OMIM: gene MIM:617747 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002135_1	Nicotine use	5.000000e-06
GCST003542_13	Night sleep phenotypes	8.000000e-06
GCST005860_3	Cholangiocarcinoma in primary sclerosing cholangitis (time to event)	1.000000e-06
GCST90002389_8	Lymphocyte percentage of white cells	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005430	nicotine use
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105997 (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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases abundance, increases expression	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Vehicle Emissions	decreases expression, decreases reaction, increases abundance, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Nickel	increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression, decreases reaction	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects binding, increases reaction	1
geraniol	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	increases expression, affects cotreatment	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Arsenic	increases abundance, increases expression	1
Demecolcine	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Potassium Dichromate	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4051569	Binding	Inhibition of SP140L (unknown origin) assessed as change in melting temperature at 10 uM by SYPRO Orange-dye based fluorescence thermal shift assay	Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and TAF1/TAF1L Bromodomains. — J Med Chem

Clinical trials (associated diseases)

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