SPIB

Summary

SPIB (Spi-B transcription factor, HGNC:11242) is a protein-coding gene on chromosome 19q13.33, encoding Transcription factor Spi-B (Q01892). Sequence specific transcriptional activator which binds to the PU-box, a purine-rich DNA sequence (5’-GAGGAA-3’) that can act as a lymphoid-specific enhancer.

The protein encoded by this gene is a transcriptional activator that binds to the PU-box (5’-GAGGAA-3’) and acts as a lymphoid-specific enhancer. Four transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6689 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 50 total
• Phenotypes (HPO): 41
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_003121

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11242
Approved symbol	SPIB
Name	Spi-B transcription factor
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	SPI-B
Ensembl gene	ENSG00000269404
Ensembl biotype	protein_coding
OMIM	606802
Entrez	6689

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000270632, ENST00000439922, ENST00000594188, ENST00000594685, ENST00000595883, ENST00000596074, ENST00000597855, ENST00000599923

RefSeq mRNA: 4 — MANE Select: NM_003121 NM_001243998, NM_001243999, NM_001244000, NM_003121

CCDS: CCDS33080, CCDS58674, CCDS59412

Canonical transcript exons

ENST00000595883 — 6 exons

Exon	Start	End
ENSE00002245270	50418938	50418985
ENSE00003028010	50428038	50431314
ENSE00003487299	50419946	50419973
ENSE00003511850	50422473	50422545
ENSE00003577945	50422823	50423037
ENSE00003705876	50423605	50423755

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 93.39.

FANTOM5 (CAGE): breadth broad, TPM avg 6.6418 / max 829.3723, expressed in 320 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177146	6.6418	320

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	93.39	gold quality
mucosa of transverse colon	UBERON:0004991	92.89	gold quality
vermiform appendix	UBERON:0001154	92.56	gold quality
caecum	UBERON:0001153	88.91	gold quality
granulocyte	CL:0000094	88.55	gold quality
buccal mucosa cell	CL:0002336	88.38	gold quality
spleen	UBERON:0002106	87.70	gold quality
rectum	UBERON:0001052	86.08	gold quality
ileal mucosa	UBERON:0000331	84.08	gold quality
epithelium of nasopharynx	UBERON:0001951	83.64	gold quality
nasopharynx	UBERON:0001728	83.62	gold quality
colonic mucosa	UBERON:0000317	82.24	gold quality
blood	UBERON:0000178	81.04	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.02	gold quality
transverse colon	UBERON:0001157	78.84	gold quality
small intestine	UBERON:0002108	77.53	gold quality
superficial temporal artery	UBERON:0001614	77.50	gold quality
duodenum	UBERON:0002114	77.09	gold quality
bone marrow	UBERON:0002371	76.56	gold quality
tonsil	UBERON:0002372	76.28	gold quality
leukocyte	CL:0000738	74.84	gold quality
bone marrow cell	CL:0002092	74.82	gold quality
type B pancreatic cell	CL:0000169	74.65	gold quality
olfactory bulb	UBERON:0002264	74.47	gold quality
Brodmann (1909) area 10	UBERON:0013541	74.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.95	gold quality
colonic epithelium	UBERON:0000397	73.86	gold quality
thymus	UBERON:0002370	73.51	silver quality
mononuclear cell	CL:0000842	73.41	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	1309.69
E-MTAB-8410	yes	1042.71
E-GEOD-125970	yes	742.06
E-MTAB-9067	yes	678.34
E-CURD-77	yes	386.60
E-CURD-122	yes	95.78
E-HCAD-4	yes	58.73
E-HCAD-6	yes	43.19
E-CURD-112	yes	37.12
E-MTAB-9467	yes	26.79
E-MTAB-6701	yes	19.34
E-HCAD-1	yes	16.82
E-HCAD-10	yes	16.10
E-MTAB-10042	yes	13.65
E-MTAB-8498	yes	13.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
BLNK	Activation
BTK	Repression
CD40	Activation
CREBBP
DCN
FCER1G
FCER2	Activation
GRAP2
IFNA1
IL10	Activation
IL7	Activation
IRF7	Repression
PDLIM7
PRDM1	Repression
SPIB
TERT
TNFSF10	Activation
XBP1	Unknown

JASPAR motifs

Motif	Name	Family
MA0081.1	SPIB	Ets-related
MA0081.2	SPIB	Ets-related
MA0081.3	SPIB	Ets-related

JASPAR matrix evidence (PMIDs): PMID:7624145

Upstream regulators (CollecTRI, top): BCL6, JUN, MITF, PAX5, POU2AF1, POU2F2, SPI1, SPIB

miRNA regulators (miRDB)

84 targeting SPIB, 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-5193	100.00	67.26	1744
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-1275	99.47	67.90	2749

Literature-anchored findings (GeneRIF, showing 27)

• Spi-B is expressed in plasmacytoid dendritic cell precursors and inhibits T-, B-, and NK-cell development (PMID:12393575)
• Spi-B is a key regulator of human pDC development. (PMID:15583020)
• c-Myb and c-Ets family members (Ets-1/2, PU.1, and Spi-B) control hGR 1A promoter regulation in T- and B-lymphoblast cells (PMID:16263717)
• DL1-induced activation of the Notch1 pathway controls the lineage commitment of early thymic precursors by altering the levels between Spi-B and GATA-3. (PMID:16317090)
• By chromatin immunoprecipitation and assays using an inducible Spi-B construct BLIMP1 and XBP-1 were identified as direct target genes of Spi-B mediated repression. (PMID:18552212)
• findings suggest that the concurrent action of Spi-B and E2-2 controls the development of progenitor cells into the plasmacytoid dendritic cell lineage (PMID:18792017)
• These results suggest that Spi-B could regulate JC virus gene expression in susceptible cells, and may play an important role in JC virus activity in the immune and nervous systems. (PMID:20826618)
• The effect of mutating Spi-B-binding sites within the JC virus promoter/enhancer on early viral gene expression strongly suggests a role for Spi-B binding to the viral promoter/enhancer in the activation of early viral gene expression. (PMID:22071512)
• Fine mapping identified 26 single-nucleotide polymorphisms (SNPs) across the CLEC16A-SOCS1 and 11 SNPs across the SPIB locus with significant association to primary biliary cirrhosis. (PMID:22257840)
• The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1. (PMID:22510878)
• Data show that in a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNbeta production. (PMID:22698399)
• Our data indicate that the CBFbeta-SMMHC’s C-terminus is essential to induce embryonic hematopoietic defects and leukemogenesis. (PMID:23165482)
• The SRC family tyrosine kinase HCK and the ETS family transcription factors SPIB and EHF regulate transcytosis across a human follicle-associated epithelium model. (PMID:23439650)
• Findings establish a molecular hierarchy among POU2F2, SPIB and ID2 during B-cell differentiation, and suggest that aberrant expression of these transcription factors plays an important role in arresting plasmacytic differentiation in WM. (PMID:24801987)
• our data indicate that SPIB expression is a clinically novel poor prognostic factor in DLBCL that contributes to treatment resistance, at least in part, through an anti-apoptotic mechanism. (PMID:27348272)
• High SPIB expression is associated with Lung Cancer metastasis. (PMID:28754672)
• These results show that the mechanism of action of lenalidomide in ABC-DLBCL cells involves downregulation of SPIB transcription by cereblon-induced degradation of IKAROS. (PMID:28893618)
• Results provide evidence that SPIB is a specific transcription factor that participates in pH-mediated regulation of AQP1 gene expression. (PMID:29554889)
• Taken together, this study identifies SPIB as an important target of ETV6-RUNX1 in regulation of B-cell gene expression in t(12;21) leukemia. (PMID:30986496)
• SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells. (PMID:32129936)
• SPIB acts as a tumor suppressor by activating the NFkB and JNK signaling pathways through MAP4K1 in colorectal cancer cells. (PMID:34530056)
• SPI1-related protein inhibits cervical cancer cell progression and prevents macrophage cell migration. (PMID:35770729)
• Integrated transcriptomic and regulatory network analyses uncovers the role of let-7b-5p, SPIB, and HLA-DPB1 in sepsis. (PMID:35831411)
• Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB. (PMID:35969172)
• Peroxiredoxin2 regulates trophoblast proliferation and migration through SPIB-HDAC2 pathway. (PMID:36400181)
• SPIB Knockdown Inhibits the Immune Escape of Ovarian Cancer Cells by Reducing PD-L1 (CD274) Expression and Inactivating the JAK/STAT Pathway. (PMID:37452634)
• IGSF10 inhibits the metastasis of lung adenocarcinoma via the Spi-B/Integrin-beta1 signaling pathway. (PMID:38622980)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	spi1a	ENSDARG00000067797
mus_musculus	Spib	ENSMUSG00000008193
rattus_norvegicus	Spib	ENSRNOG00000019660

Paralogs (28): ETV1 (ENSG00000006468), ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ELF4 (ENSG00000102034), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELF2 (ENSG00000109381), ELK3 (ENSG00000111145), ETV3 (ENSG00000117036), ELF1 (ENSG00000120690), SPDEF (ENSG00000124664), ELK1 (ENSG00000126767), ETS1 (ENSG00000134954), EHF (ENSG00000135373), ELF5 (ENSG00000135374), ETV6 (ENSG00000139083), FLI1 (ENSG00000151702), GABPA (ENSG00000154727), ERG (ENSG00000157554), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), ELF3 (ENSG00000163435), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041)

Protein

Protein identifiers

Transcription factor Spi-B — Q01892 (reviewed: Q01892)

All UniProt accessions (4): Q01892, M0QXA8, M0R037, M0R2J9

UniProt curated annotations — full annotation on UniProt →

Function. Sequence specific transcriptional activator which binds to the PU-box, a purine-rich DNA sequence (5’-GAGGAA-3’) that can act as a lymphoid-specific enhancer. Promotes development of plasmacytoid dendritic cells (pDCs), also known as type 2 DC precursors (pre-DC2) or natural interferon (IFN)-producing cells. These cells have the capacity to produce large amounts of interferon and block viral replication. May be required for B-cell receptor (BCR) signaling, which is necessary for normal B-cell development and antigenic stimulation.

Subunit / interactions. Can form homotypic interactions. Interacts with IRF4/Pip. Interacts with JUN. Interacts with TBP. May also interact with CREBBP and EP300. Interacts with NONO/p54(nrb).

Subcellular location. Nucleus Cytoplasm.

Tissue specificity. Expressed in plasmacytoid dendritic cells (pDCs) and B-cells, not expressed in T-cells or granulocytes. May also be enriched in stem cell populations of the liver.

Domain organisation. The protein contains a weakly acidic N-terminal transactivation domain (TAD) followed by a second TAD rich in proline, serine and threonine. Each of these domains may be required for transcriptional activation of a subset of target genes.

Similarity. Belongs to the ETS family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q01892-1	1	yes
Q01892-2	2, DeltaSpi-B
Q01892-3	3

RefSeq proteins (4): NP_001230927, NP_001230928, NP_001230929, NP_003112* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR046328	ETS_fam	Family

Pfam: PF00178

UniProt features (14 total): mutagenesis site 4, splice variant 4, region of interest 3, chain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01892-F1	68.20	0.36

Functional residue map

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

Mutagenesis-validated functional residues (4):

Position	Phenotype
37	no effect on transcriptional activation.
56	no effect on transcriptional activation.
144	reduces interaction with irf4 and transcriptional activation.
242	abrogates dna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 362 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, RNGTGGGC_UNKNOWN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, HNF3ALPHA_Q6, GOBP_B_CELL_ACTIVATION, XU_GH1_AUTOCRINE_TARGETS_UP, RACCACAR_AML_Q6, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, CAGCTG_AP4_Q5, TTGCWCAAY_CEBPB_02, CEBPB_01, NFKB_Q6, BLALOCK_ALZHEIMERS_DISEASE_UP, HEN1_01, SHIN_B_CELL_LYMPHOMA_CLUSTER_9

GO Biological Process (6): immature B cell differentiation (GO:0002327), regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), macrophage differentiation (GO:0030225), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
B cell differentiation	1
cellular developmental process	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
DNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPIB	IRF4	Q15306	864
SPIB	IRF7	Q92985	844
SPIB	POU2AF1	Q16633	815
SPIB	IRF8	Q02556	805
SPIB	PAX5	Q02548	750
SPIB	IKZF3	Q9UKT9	734
SPIB	EBF1	Q9UH73	705
SPIB	NFIA	Q12857	649
SPIB	BATF	Q16520	630
SPIB	SATB1	Q01826	623
SPIB	CD19	P15391	618
SPIB	TNFSF11	O14788	580
SPIB	FLT3LG	P49771	577
SPIB	PTPRC	P08575	575
SPIB	CSF1R	P07333	550

IntAct

36 interactions, top by confidence:

A	B	Type	Score
SPIB		psi-mi:“MI:0915”(physical association)	0.560
HTT	SPIB	psi-mi:“MI:0915”(physical association)	0.560
	SPIB	psi-mi:“MI:0915”(physical association)	0.370
CCL24	SPIB	psi-mi:“MI:0915”(physical association)	0.370
IFNA2	SPIB	psi-mi:“MI:0915”(physical association)	0.370
IL18	SPIB	psi-mi:“MI:0915”(physical association)	0.370
IL23A	SPIB	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (20): Crebbp (Reconstituted Complex), EP300 (Reconstituted Complex), SPIB (Reconstituted Complex), SPIB (Affinity Capture-Western), SPIB (Two-hybrid), SPIB (Two-hybrid), SPIB (Two-hybrid), SPIB (Two-hybrid), SPIB (Biochemical Activity), MAPK3 (Co-purification), MAPK8 (Co-purification), SPIB (Biochemical Activity), SPIB (Biochemical Activity), SPIB (Reconstituted Complex), TBP (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GUS0, A1YF56, A2AKB4, A6NI15, A7E346, D3Z9H7, D3ZJK7, O00321, O35906, O88286, O94983, O95785, P17433, P17947, P70298, P70327, P97309, Q01892, Q0ZCJ7, Q14934, Q3U1J1, Q5EBA3, Q61660, Q63247, Q6BDS1, Q6PAJ3, Q6PKU1, Q6ZMQ8, Q6ZN01, Q6ZVH7, Q75VX8, Q80Y50, Q80YE4, Q8BG26, Q8BGD7, Q8CJH6, Q8IUM7, Q8K120, Q91XE9, Q92949

Diamond homologs: A0A1W2PQ73, A0JN51, A1A4L6, A1YF15, A1YG61, A1YG91, A2D4Z7, A2T737, A2T762, A3FEM2, A4GTP4, A8WFJ9, O00321, O01519, O35906, O70132, O70273, O95238, P01105, P10157, P11308, P11536, P13474, P14921, P15036, P15037, P15062, P17433, P17947, P18755, P18756, P19102, P19419, P20105, P27577, P28322, P28324, P29773, P29774, P29775

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CSNK2A2	“down-regulates quantity by destabilization”	SPIB	phosphorylation
MAPK3	unknown	SPIB	phosphorylation
CSNK2A1	down-regulates	SPIB	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

924 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50418981:GCACA:G	donor_gain	1.0000
19:50418986:G:GG	donor_gain	1.0000
19:50422458:T:TA	acceptor_gain	1.0000
19:50422461:A:AG	acceptor_gain	1.0000
19:50422461:ACCCC:A	acceptor_gain	1.0000
19:50422462:C:G	acceptor_gain	1.0000
19:50422468:A:AG	acceptor_gain	1.0000
19:50422471:A:AG	acceptor_gain	1.0000
19:50422472:G:GG	acceptor_gain	1.0000
19:50422542:CCTGG:C	donor_loss	1.0000
19:50422543:CTGGT:C	donor_loss	1.0000
19:50422544:TGG:T	donor_loss	1.0000
19:50422544:TGGTG:T	donor_loss	1.0000
19:50422545:GGT:G	donor_loss	1.0000
19:50422545:GGTG:G	donor_loss	1.0000
19:50422546:G:GG	donor_gain	1.0000
19:50422546:GT:G	donor_loss	1.0000
19:50422547:T:G	donor_loss	1.0000
19:50428033:C:A	acceptor_gain	1.0000
19:50428033:CGCA:C	acceptor_loss	1.0000
19:50428034:GCAG:G	acceptor_loss	1.0000
19:50428035:CA:C	acceptor_loss	1.0000
19:50428036:A:AG	acceptor_gain	1.0000
19:50428036:A:G	acceptor_loss	1.0000
19:50428036:AG:A	acceptor_gain	1.0000
19:50428036:AGG:A	acceptor_gain	1.0000
19:50428037:G:GA	acceptor_loss	1.0000
19:50428037:G:GG	acceptor_gain	1.0000
19:50428037:GG:G	acceptor_gain	1.0000
19:50428037:GGG:G	acceptor_gain	1.0000

AlphaMissense

1678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50428067:T:C	F174L	1.000
19:50428068:T:C	F174S	1.000
19:50428068:T:G	F174C	1.000
19:50428069:C:A	F174L	1.000
19:50428069:C:G	F174L	1.000
19:50428117:G:C	W190C	1.000
19:50428117:G:T	W190C	1.000
19:50428139:T:C	F198L	1.000
19:50428140:T:C	F198S	1.000
19:50428141:C:A	F198L	1.000
19:50428141:C:G	F198L	1.000
19:50428145:T:C	F200L	1.000
19:50428146:T:C	F200S	1.000
19:50428146:T:G	F200C	1.000
19:50428147:C:A	F200L	1.000
19:50428147:C:G	F200L	1.000
19:50428162:G:C	K205N	1.000
19:50428162:G:T	K205N	1.000
19:50428181:T:A	W212R	1.000
19:50428181:T:C	W212R	1.000
19:50428182:G:C	W212S	1.000
19:50428183:G:C	W212C	1.000
19:50428183:G:T	W212C	1.000
19:50428185:G:A	G213D	1.000
19:50428195:G:C	K216N	1.000
19:50428195:G:T	K216N	1.000
19:50428212:T:C	M222T	1.000
19:50428212:T:G	M222R	1.000
19:50428213:G:A	M222I	1.000
19:50428213:G:C	M222I	1.000

dbSNP variants (sampled 300 via entrez): RS1000388561 (19:50418396 G>A), RS1000557219 (19:50428066 G>A), RS1000578849 (19:50429096 T>C), RS1000913420 (19:50418083 C>T), RS1001182092 (19:50427695 T>G), RS1001349661 (19:50418345 G>A), RS1001419254 (19:50417725 G>A,C,T), RS1001787004 (19:50417659 G>A), RS1001965893 (19:50431544 T>C,G), RS1002147708 (19:50427966 G>A,C), RS1002149264 (19:50426134 A>G), RS1002275822 (19:50420654 G>GTC), RS1002308329 (19:50420842 G>A), RS1002806549 (19:50417483 C>A), RS1003000253 (19:50430536 A>C,G)

Disease associations

OMIM: gene MIM:606802 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000820	Abnormality of the thyroid gland
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000953	Hyperpigmentation of the skin
HP:0000989	Pruritus
HP:0001114	Xanthelasma
HP:0001262	Excessive daytime somnolence
HP:0001278	Orthostatic hypotension
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001399	Hepatic failure
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0002040	Esophageal varix
HP:0002240	Hepatomegaly
HP:0002360	Sleep disturbance
HP:0002480	Hepatic encephalopathy
HP:0002570	Steatorrhea
HP:0002608	Celiac disease
HP:0002613	Biliary cirrhosis
HP:0002841	Recurrent fungal infections
HP:0002908	Conjugated hyperbilirubinemia
HP:0002960	Autoimmunity
HP:0003073	Hypoalbuminemia
HP:0003119	Abnormal circulating lipid concentration
HP:0003124	Hypercholesterolemia
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003261	Increased circulating IgA concentration

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000733_1	Primary biliary cholangitis	8.000000e-11
GCST001010_5	Primary biliary cholangitis	2.000000e-13
GCST003129_10	Primary biliary cholangitis	1.000000e-20
GCST006624_24	Systolic blood pressure	2.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
monobutyl phthalate	increases methylation	1
2-palmitoylglycerol	increases expression	1
(+)-JQ1 compound	increases expression	1
Irinotecan	increases expression	1
Arsenic Trioxide	decreases expression	1
Allergens	increases expression	1
Arsenic	decreases response to substance	1
Curcumin	increases expression	1
Nickel	increases expression	1
Phosphorus	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_8800	OCI-Ly3	Cancer cell line	Male
CVCL_A6Q0	SEES3-1V human SPIB, clone1	Embryonic stem cell	Male
CVCL_A6Q1	SEES3-1V human SPIB, clone2	Embryonic stem cell	Male
CVCL_A6Q2	SEES3-1V human SPIB, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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