ZBTB7B

Summary

ZBTB7B (zinc finger and BTB domain containing 7B, HGNC:18668) is a protein-coding gene on chromosome 1q21.3, encoding Zinc finger and BTB domain-containing protein 7B (O15156). Transcription regulator that acts as a key regulator of lineage commitment of immature T-cell precursors.

This gene encodes a zinc finger-containing transcription factor that acts as a key regulator of lineage commitment of immature T-cell precursors. It is necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. It also functions as a transcriptional repressor of type I collagen genes. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 51043 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 20 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Transcription factor: yes — 16 downstream targets (CollecTRI)
• MANE Select transcript: NM_001256455

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18668
Approved symbol	ZBTB7B
Name	zinc finger and BTB domain containing 7B
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	ZBTB15, c-Krox, hcKrox, ZNF857B, vGAF, ThPOK
Ensembl gene	ENSG00000160685
Ensembl biotype	protein_coding
OMIM	607646
Entrez	51043

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 51 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000292176, ENST00000368426, ENST00000417934, ENST00000483226, ENST00000535420, ENST00000890634, ENST00000890635, ENST00000890636, ENST00000890637, ENST00000890638, ENST00000890639, ENST00000890640, ENST00000890641, ENST00000890642, ENST00000890643, ENST00000890644, ENST00000890645, ENST00000890646, ENST00000890647, ENST00000890648, ENST00000890649, ENST00000890650, ENST00000890651, ENST00000890652, ENST00000890653, ENST00000890654, ENST00000890655, ENST00000890656, ENST00000890657, ENST00000890658, ENST00000890659, ENST00000890660, ENST00000890661, ENST00000890662, ENST00000890663, ENST00000890664, ENST00000890665, ENST00000890666, ENST00000890667, ENST00000890668, ENST00000890669, ENST00000890670, ENST00000890671, ENST00000890672, ENST00000916801, ENST00000916802, ENST00000916803, ENST00000963979, ENST00000963980, ENST00000963981, ENST00000963982, ENST00000963983

RefSeq mRNA: 7 — MANE Select: NM_001256455 NM_001252406, NM_001256455, NM_001377451, NM_001377452, NM_001377453, NM_001377454, NM_001377455

CCDS: CCDS1081, CCDS58030

Canonical transcript exons

ENST00000535420 — 3 exons

Exon	Start	End
ENSE00001935182	155002802	155002943
ENSE00003485987	155014655	155015814
ENSE00003937020	155016220	155018523

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2912 / max 128.7205, expressed in 1627 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5554	4.9968	1475
5552	1.8458	834
5553	0.4486	187

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.67	gold quality
monocyte	CL:0000576	97.51	gold quality
mucosa of transverse colon	UBERON:0004991	97.40	gold quality
skin of abdomen	UBERON:0001416	97.29	gold quality
skin of leg	UBERON:0001511	97.25	gold quality
mononuclear cell	CL:0000842	97.08	gold quality
leukocyte	CL:0000738	97.00	gold quality
granulocyte	CL:0000094	96.96	gold quality
esophagus mucosa	UBERON:0002469	96.00	gold quality
transverse colon	UBERON:0001157	95.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.00	gold quality
zone of skin	UBERON:0000014	94.52	gold quality
small intestine	UBERON:0002108	93.79	gold quality
nipple	UBERON:0002030	93.78	gold quality
cardia of stomach	UBERON:0001162	93.62	gold quality
body of stomach	UBERON:0001161	93.53	gold quality
saliva-secreting gland	UBERON:0001044	93.47	gold quality
pharyngeal mucosa	UBERON:0000355	93.46	gold quality
minor salivary gland	UBERON:0001830	93.39	gold quality
right adrenal gland cortex	UBERON:0035827	93.39	gold quality
right adrenal gland	UBERON:0001233	93.22	gold quality
parotid gland	UBERON:0001831	93.16	gold quality
rectum	UBERON:0001052	93.11	gold quality
body of tongue	UBERON:0011876	93.08	gold quality
esophagus	UBERON:0001043	93.02	gold quality
vena cava	UBERON:0004087	92.68	silver quality
right lobe of liver	UBERON:0001114	92.67	gold quality
adrenal cortex	UBERON:0001235	92.53	gold quality
mouth mucosa	UBERON:0003729	92.49	gold quality
left adrenal gland	UBERON:0001234	92.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	371.55
E-ANND-3	no	4.57

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

16 targets.

Target	Regulation
ADRA1D
CD4	Activation
CD8A	Repression
CDCP1
COL1A1
COL1A2
COL2A1	Activation
ELN
FN1	Repression
HLA-E
IFNG
MPPED2
SERPINA3
TOX
UGDH	Unknown
ZBTB7B

JASPAR motifs

Motif	Name	Family
MA0694.1	ZBTB7B	More than 3 adjacent zinc fingers
MA0694.2	ZBTB7B	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:19443739

Upstream regulators (CollecTRI, top): GATA3, ZBTB7B

Literature-anchored findings (GeneRIF, showing 20)

• These data suggest that the regulation of COL1A1 gene transcription in human dermal fibroblasts involves a complex machinery that implicates at least three transcription proteins, hc-Krox, Sp1, and Sp3. (PMID:17698844)
• Chondroitin sulphate and its derived hydrolytic fragments (CSf) repress COL1A1 gene transcription through a -112/-61 bp sequence upstream the start site of transcription and imply hc-Krox and Sp1 transcription factors. (PMID:18298657)
• Runx and ThPOK role in mechanisms of lineage-specific gene regulation in the process of T-cell commitments[review] (PMID:19479890)
• Thymoma neoplastic epithelial cells can induce Th-POK expression in T-cell subsets similarly to the normal thymic epithelial cells. In addition, there was no significant difference in Runx3 expression in T-cell subsets between normal thymi and thymomas. (PMID:19886737)
• impairment of Lck-mediated CD4 coreceptor signaling by Nef is an important in vivo mechanism of HIV-1 pathogenesis (PMID:20810990)
• comparing the promoter regions of the Th-POK gene between human and mouse, the region 3600 base pairs upstream from the transcription initiation site of the Th-POK gene was highly conserved (PMID:20847520)
• The p65 subunit of NF-kappaB inhibits COL1A1 gene transcription in human dermal and scleroderma fibroblasts through its recruitment on promoter by protein interaction with transcriptional activators (c-Krox, Sp1, and Sp3). (PMID:22139845)
• ThPOK transgene stably represses CD8 gene expression through the deacetylation of Cd8 loci in CD4 cell lineage commitment. (PMID:22730529)
• The distal regulatory element (DRE) in the Thpok gene also functions as a transcriptional enhancer, with DNA sequences specifically responsible for thymic enhancer activity. (PMID:23315079)
• ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells. (PMID:23349906)
• a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNgamma production, which could contribute to the regulation of inflammation. (PMID:23609452)
• In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. (PMID:29488879)
• Authors show that the transcription factor ThPOK binds cooperatively with NF-kappaB to NRCs and mediates their physical proximity with the IFNB1 gene via its ability to oligomerize when bound to DNA. (PMID:30017585)
• Interactome of vertebrate GAF/ThPOK reveals its diverse functions in gene regulation and DNA repair. (PMID:32098917)
• Zbtb7b suppresses aseptic inflammation by regulating m(6)A modification of IL6 mRNA. (PMID:32828308)
• Zbtb7a and Zbtb7b: Opening naive loci to reprogram ESCs. (PMID:33627571)
• ThPOK transcriptionally inactivates TNFRSF12A to increase the proliferation of T cells with the involvement of the NF-kB pathway. (PMID:34353698)
• Epigenetic DNA methylation of Zbtb7b regulates the population of double-positive CD4(+)CD8(+) T cells in ulcerative colitis. (PMID:35761286)
• A novel high-risk subpopulation identified by CTSL and ZBTB7B in gastric cancer. (PMID:35941174)
• ALDH1A1 promotes immune escape of tumor cells through ZBTB7B-glycolysis pathway. (PMID:39107297)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb7b	ENSDARG00000021891
mus_musculus	Zbtb7b	ENSMUSG00000028042
rattus_norvegicus	Zbtb7b	ENSRNOG00000020640

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 7B — O15156 (reviewed: O15156)

Alternative names: Krueppel-related zinc finger protein cKrox, T-helper-inducing POZ/Krueppel-like factor, Zinc finger and BTB domain-containing protein 15, Zinc finger protein 67 homolog, Zinc finger protein 857B, Zinc finger protein Th-POK

All UniProt accessions (1): O15156

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator that acts as a key regulator of lineage commitment of immature T-cell precursors. Exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively. Cross-antagonism between ZBTB7B and CBF complexes are determinative to CD4 versus CD8 cell fate decision. Suppresses RUNX3 expression and imposes CD4+ lineage fate by inducing the SOCS suppressors of cytokine signaling. induces, as a transcriptional activator, SOCS genes expression which represses RUNX3 expression and promotes the CD4+ lineage fate. During CD4 lineage commitment, associates with multiple sites at the CD8 locus, acting as a negative regulator of the CD8 promoter and enhancers by epigenetic silencing through the recruitment of class II histone deacetylases, such as HDAC4 and HDAC5, to these loci. Regulates the development of IL17-producing CD1d-restricted naural killer (NK) T cells. Also functions as an important metabolic regulator in the lactating mammary glands. Critical feed-forward regulator of insulin signaling in mammary gland lactation, directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Transcriptional repressor of the collagen COL1A1 and COL1A2 genes. May also function as a repressor of fibronectin and possibly other extracellular matrix genes. Potent driver of brown fat development, thermogenesis and cold-induced beige fat formation. Recruits the brown fat lncRNA 1 (Blnc1):HNRNPU ribonucleoprotein complex to activate thermogenic gene expression in brown and beige adipocytes.

Subunit / interactions. Homodimerizes. Interacts with NCL, NEDD4 and YBX1. Interacts with HNRNPU (via RNA-binding RGG-box region); the interaction facilitates the recruitment of long non-coding RNA Blnc1 by ZBTB7B. Interacts with HDAC4 and HDAC5; the interaction allows the recruitment of HDAC4 and HDAC5 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression.

Subcellular location. Nucleus.

Post-translational modifications. Acetylated directly and specifically by EP300. EP300-mediated acetylation of Lys-206, Lys-212 and Lys-335 stabilizes the protein by antagonizing ubiquitin conjugation. Ubiquitinated, leading to proteasomal degradation. Competes with acetylation on Lys-206, Lys-212 and Lys-335.

Isoforms (2)

UniProt ID	Names	Canonical?
O15156-1	1	yes
O15156-2	2

RefSeq proteins (7): NP_001239335, NP_001243384, NP_001364380, NP_001364381, NP_001364382, NP_001364383, NP_001364384 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050457	ZnFinger_BTB_dom_contain	Family

Pfam: PF00096, PF00651

UniProt features (28 total): modified residue 5, sequence conflict 5, compositionally biased region 4, zinc finger region 4, region of interest 4, cross-link 3, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15156-F1	56.36	0.01

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 (8): 150, 206, 212, 335, 369, 206, 212, 335

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 280 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION

GO Biological Process (24): negative regulation of transcription by RNA polymerase II (GO:0000122), NK T cell differentiation (GO:0001865), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), ectoderm development (GO:0007398), lactation (GO:0007595), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of interleukin-17 production (GO:0032740), response to insulin (GO:0032868), positive regulation of CD4-positive, alpha-beta T cell differentiation (GO:0043372), negative regulation of CD8-positive, alpha-beta T cell differentiation (GO:0043377), positive regulation of insulin receptor signaling pathway (GO:0046628), negative regulation of NK T cell proliferation (GO:0051141), positive regulation of brown fat cell differentiation (GO:0090336), positive regulation of cold-induced thermogenesis (GO:0120162), adaptive thermogenesis (GO:1990845), negative regulation of T-helper 17 cell differentiation (GO:2000320), positive regulation of SREBP signaling pathway (GO:2000640), regulation of gene expression (GO:0010468), cell differentiation (GO:0030154), regulation of CD8-positive, alpha-beta T cell differentiation (GO:0043376), regulation of T-helper cell differentiation (GO:0045622), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (14): 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 repressor activity (GO:0001217), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleoplasm (GO:0005654), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription cis-regulatory region binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of gene expression	2
DNA-binding transcription factor activity	2
alpha-beta T cell differentiation	1
DNA-templated transcription	1
tissue development	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
positive regulation of cytokine production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
response to peptide hormone	1
CD4-positive, alpha-beta T cell differentiation	1
regulation of CD4-positive, alpha-beta T cell differentiation	1
positive regulation of alpha-beta T cell differentiation	1
positive regulation of CD4-positive, alpha-beta T cell activation	1
CD8-positive, alpha-beta T cell differentiation	1
regulation of CD8-positive, alpha-beta T cell differentiation	1
negative regulation of alpha-beta T cell differentiation	1
negative regulation of CD8-positive, alpha-beta T cell activation	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
NK T cell proliferation	1
negative regulation of alpha-beta T cell proliferation	1
negative regulation of NK T cell activation	1
regulation of NK T cell proliferation	1
positive regulation of fat cell differentiation	1
brown fat cell differentiation	1
regulation of brown fat cell differentiation	1

Protein interactions and networks

STRING

1510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB7B	CDCP1	Q9H5V8	900
ZBTB7B	HNRNPU	Q00839	868
ZBTB7B	RUNX3	Q13761	813
ZBTB7B	CD4	P01730	600
ZBTB7B	GATA3	P23771	595
ZBTB7B	CD8A	P01732	583
ZBTB7B	TBX21	Q9UL17	579
ZBTB7B	RUNX1	Q01196	518
ZBTB7B	EOMES	O95936	485
ZBTB7B	COL1A1	P02452	484
ZBTB7B	EBF2	Q9HAK2	477
ZBTB7B	HDAC3	O15379	474
ZBTB7B	FOXP3	Q9BZS1	473
ZBTB7B	MEIS1	O00470	460
ZBTB7B	CBFB	Q13951	447

IntAct

53 interactions, top by confidence:

A	B	Type	Score
ZBTB7B	IMP4	psi-mi:“MI:0915”(physical association)	0.670
IMP4	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.670
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
ZBTB7B	ZBTB5	psi-mi:“MI:0915”(physical association)	0.560
NCK2	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7B	SORBS3	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7B	RPL9	psi-mi:“MI:0915”(physical association)	0.560
BCL6	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
GRB2	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
PIN1	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
MORF4L2	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
SYTL4	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
SH3YL1	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7B	BCL6	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7B	GRB2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7B	SYTL4	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7B	NCK2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (89): ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), ZBTB7B (Two-hybrid), IMP4 (Two-hybrid), SYTL4 (Two-hybrid), ZBTB7B (Affinity Capture-MS), ZBTB7B (Two-hybrid), IMP4 (Two-hybrid)

ESM2 similar proteins: A0A0G2JUG7, A1YER5, A1YFY1, A2T6X5, B2DD29, C0HBT3, O08629, O15156, O15169, O35730, O60307, O95343, P0C0T2, P28702, P28704, P29353, P50241, P98083, Q06587, Q0IHB0, Q13263, Q2V2M9, Q2YDU3, Q3U1V8, Q3U2S4, Q4KMP7, Q5DU25, Q5JU85, Q5PRF9, Q5R7W7, Q5RBI7, Q5RJI5, Q5TJF3, Q5TJF7, Q62233, Q62318, Q66J69, Q68DC2, Q6MGB6, Q6ZRS2

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — UCS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1156 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155014653:A:AG	acceptor_gain	1.0000
1:155014654:G:GG	acceptor_gain	1.0000
1:155015814:GGTG:G	donor_loss	1.0000
1:155015815:G:C	donor_loss	1.0000
1:155016208:T:A	acceptor_gain	1.0000
1:155002939:GAGAG:G	donor_gain	0.9900
1:155002941:GAG:G	donor_gain	0.9900
1:155002941:GAGGT:G	donor_loss	0.9900
1:155002943:GGT:G	donor_loss	0.9900
1:155002944:G:GC	donor_loss	0.9900
1:155002944:G:GG	donor_gain	0.9900
1:155002945:T:A	donor_loss	0.9900
1:155014092:GT:G	donor_gain	0.9900
1:155014641:ACTT:A	acceptor_gain	0.9900
1:155014650:TGCAG:T	acceptor_loss	0.9900
1:155014651:GCAGG:G	acceptor_loss	0.9900
1:155014654:GGA:G	acceptor_gain	0.9900
1:155014654:GGAGA:G	acceptor_gain	0.9900
1:155015815:G:GG	donor_gain	0.9900
1:155016203:A:AG	acceptor_gain	0.9900
1:155016204:C:G	acceptor_gain	0.9900
1:155016212:T:A	acceptor_gain	0.9900
1:155016214:T:TA	acceptor_gain	0.9900
1:155016216:CCA:C	acceptor_loss	0.9900
1:155016217:CA:C	acceptor_loss	0.9900
1:155016218:A:AG	acceptor_gain	0.9900
1:155016218:A:AT	acceptor_loss	0.9900
1:155016218:AG:A	acceptor_gain	0.9900
1:155016219:G:GG	acceptor_gain	0.9900
1:155016219:GG:G	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000163184 (1:155002011 T>C), RS1000213667 (1:155005217 G>A,C), RS1000223222 (1:155011654 T>C), RS1000432613 (1:155004747 C>T), RS1000708388 (1:155003159 C>G), RS1000765485 (1:155003384 C>A,T), RS1000840671 (1:155015597 G>C), RS1000889493 (1:155009366 G>A,T), RS1000889730 (1:155009105 A>G), RS1000942718 (1:155009621 C>G), RS1001219330 (1:155010351 C>G), RS1001880106 (1:155016169 C>G,T), RS1002228318 (1:155003672 G>T), RS1002231118 (1:155002196 A>G), RS1002772687 (1:155000594 T>C)

Disease associations

OMIM: gene MIM:607646 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST001942_19	Prostate cancer	2.000000e-08
GCST005146_14	Birth weight	1.000000e-12
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST007483_43	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-08
GCST007487_9	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-08
GCST007500_12	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-13
GCST007502_7	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-13
GCST007557_2	Birth weight	2.000000e-07
GCST008103_81	Bipolar disorder	1.000000e-06
GCST008129_60	Body mass index	8.000000e-18
GCST008870_19	Keratinocyte cancer (MTAG)	8.000000e-11
GCST008871_26	Basal cell carcinoma	3.000000e-10
GCST009597_81	Multiple sclerosis	2.000000e-08
GCST010002_367	Refractive error	5.000000e-13
GCST010796_4087	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4088	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4686	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_4687	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4688	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-10
GCST010797_2	Breast cancer, ovarian cancer or prostate cancer (pleiotropy)	5.000000e-09
GCST010988_255	Adult body size	7.000000e-13
GCST012227_1044	Hip circumference adjusted for BMI	2.000000e-08
GCST90002383_334	Hematocrit	4.000000e-24
GCST90002384_8	Hemoglobin	9.000000e-24
GCST90020024_606	A body shape index	1.000000e-12

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0004341	body fat distribution
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004340	body mass index
EFO:0010176	keratinocyte carcinoma
EFO:0004327	electrocardiography
EFO:0008039	BMI-adjusted hip circumference
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorodecanoic acid	decreases expression	1
Am 580	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
Rosiglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Arbutin	decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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