TSC22D1

Summary

TSC22D1 (TSC22 domain family member 1, HGNC:16826) is a protein-coding gene on chromosome 13q14.11, encoding TSC22 domain family protein 1 (Q15714). Transcriptional repressor.

This gene encodes a member of the TSC22 domain family of leucine zipper transcription factors. The encoded protein is stimulated by transforming growth factor beta, and regulates the transcription of multiple genes including C-type natriuretic peptide. The encoded protein may play a critical role in tumor suppression through the induction of cancer cell apoptosis, and a single nucleotide polymorphism in the promoter of this gene has been associated with diabetic nephropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 8848 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_183422

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16826
Approved symbol	TSC22D1
Name	TSC22 domain family member 1
Location	13q14.11
Locus type	gene with protein product
Status	Approved
Aliases	TSC22, MGC17597
Ensembl gene	ENSG00000102804
Ensembl biotype	protein_coding
OMIM	607715
Entrez	8848

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000261489, ENST00000437455, ENST00000458659, ENST00000460842, ENST00000472477, ENST00000486464, ENST00000487881, ENST00000493016, ENST00000496314, ENST00000496838, ENST00000611198, ENST00000622051, ENST00000871365, ENST00000871366, ENST00000871367

RefSeq mRNA: 4 — MANE Select: NM_183422 NM_001243797, NM_001243798, NM_006022, NM_183422

CCDS: CCDS31966, CCDS73565, CCDS9392

Canonical transcript exons

ENST00000458659 — 3 exons

Exon	Start	End
ENSE00001644188	44573163	44576330
ENSE00001738713	44436044	44436095
ENSE00001859700	44432143	44434883

Expression profiles

Bgee: expression breadth ubiquitous, 308 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 120.8859 / max 1812.0562, expressed in 1811 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137053	98.8019	1760
137067	8.8782	1544
137069	5.7681	1609
137054	2.4470	1077
137068	2.2304	998
137070	1.2487	591
137065	0.3850	210
137048	0.3171	178
137071	0.2101	99
137049	0.1892	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.97	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.92	gold quality
middle temporal gyrus	UBERON:0002771	99.88	gold quality
tibia	UBERON:0000979	99.73	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.69	gold quality
postcentral gyrus	UBERON:0002581	99.67	gold quality
type B pancreatic cell	CL:0000169	99.66	gold quality
entorhinal cortex	UBERON:0002728	99.66	gold quality
parietal lobe	UBERON:0001872	99.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.63	gold quality
caput epididymis	UBERON:0004358	99.59	gold quality
visceral pleura	UBERON:0002401	99.58	gold quality
primary visual cortex	UBERON:0002436	99.52	gold quality
occipital lobe	UBERON:0002021	99.51	gold quality
inferior olivary complex	UBERON:0002127	99.51	gold quality
blood vessel layer	UBERON:0004797	99.50	gold quality
cranial nerve II	UBERON:0000941	99.46	gold quality
renal glomerulus	UBERON:0000074	99.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.45	gold quality
epithelium of nasopharynx	UBERON:0001951	99.43	gold quality
olfactory bulb	UBERON:0002264	99.43	gold quality
vena cava	UBERON:0004087	99.43	gold quality
orbitofrontal cortex	UBERON:0004167	99.43	gold quality
corpus epididymis	UBERON:0004359	99.42	gold quality
adult organism	UBERON:0007023	99.42	gold quality
nasopharynx	UBERON:0001728	99.41	gold quality
choroid plexus epithelium	UBERON:0003911	99.41	gold quality
metanephric glomerulus	UBERON:0004736	99.40	gold quality
urethra	UBERON:0000057	99.39	gold quality
heart right ventricle	UBERON:0002080	99.38	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	8047.65
E-MTAB-9221	yes	5130.69
E-GEOD-100618	yes	3908.04
E-CURD-112	yes	1296.07
E-MTAB-8142	yes	145.41
E-MTAB-6701	yes	117.42
E-HCAD-4	yes	69.19
E-MTAB-10287	yes	67.84
E-CURD-119	yes	48.28
E-GEOD-134144	yes	43.66
E-HCAD-1	yes	41.74
E-HCAD-10	yes	37.94
E-CURD-88	yes	31.27
E-HCAD-6	yes	31.25
E-MTAB-8410	yes	29.51

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
ADAM2
CDKN1A
CNP	Activation
COL1A2
NPPC	Activation
PTEN
SRPRA
TSC2
TSC22D1

Upstream regulators (CollecTRI, top): CTNNB1, FOXI1, FOXO1, GLI1, TSC22D1

miRNA regulators (miRDB)

103 targeting TSC22D1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6885-3P	99.75	70.36	3187

Literature-anchored findings (GeneRIF, showing 16)

• Leucine Zipper structure of TSC22 markedly inhibits the anchorage independent growth of salivary gland cancer cells (PMID:11836610)
• TSC-22 is an important downstream component of PPARgamma and TGF-beta signaling during intestinal epithelial cell differentiation (PMID:12468551)
• findings suggest that the TSC-22 gene (-396) A allele is associated with an increasing risk of diabetic nephropathy (PMID:12757981)
• Upregulation of TSC-22 mRNA by TGF-beta 1 is achieved by mRNA stabilization. (PMID:12767908)
• Tsc-22 modulates the TGF-beta-dependant signaling pathway and binds to and modulate the transcriptional activity of Smad3 and Smad4. It has effect on cellular differentiation (PMID:15881652)
• expression of TSC-22 in prostate is restricted to basal layer; maybe useful marker for differentation between normal and malignant acinar epithelium of prostate (PMID:16106424)
• TSC-22 is a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD (PMID:17690703)
• Expression of TSC-22 was frequently observed in the tumor cells with differentiated-phenotypes, although rarely in the cells with growing potentials. (PMID:18288391)
• interaction between fortilin and TSC-22 prevents apoptosis via the destabilization of TSC-22 in ovarian carcinoma cells (PMID:18325344)
• Long form of TSC22DF is evolutionarily conserved and has growth-regulating potential. (PMID:20149264)
• Results support role of TSC22D1 as an enhancer of CNP transcription and suggest that TGF-beta-induced upregulation of CNP expression in smooth muscle may be mediated in part by increased transcription of TSC22D1. (PMID:20802130)
• Differential regulation of antagonistic TSC22D1 variants is required for the establishment of oncogene-induced cellular senescence. (PMID:21448135)
• we report that induced Tsc-22 leads to enhancement of TGF-beta-dependent signaling and enhancement is blocked by expression of a dominant-negative Tsc-22 mutant (PMID:21881999)
• TSC-22 acts as a tumor suppressor by safeguarding p53 from poly-ubiquitination mediated-degradation. (PMID:22870275)
• TSC22 could suppress tumor by inhibiting cell proliferation in colorectal cancer cell lines. Multivariate Cox regression analysis confirmed TSC22 expression as independent predictors of the OS in CRC patients (PMID:29481799)
• Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry. (PMID:34681573)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tsc22d1	ENSDARG00000038306
mus_musculus	Tsc22d1	ENSMUSG00000022010
rattus_norvegicus	Tsc22d1	ENSRNOG00000001030
drosophila_melanogaster	bun	FBGN0259176
caenorhabditis_elegans		WBGENE00011824
caenorhabditis_elegans		WBGENE00012994

Paralogs (3): TSC22D3 (ENSG00000157514), TSC22D4 (ENSG00000166925), TSC22D2 (ENSG00000196428)

Protein

Protein identifiers

TSC22 domain family protein 1 — Q15714 (reviewed: Q15714)

Alternative names: Cerebral protein 2, Regulatory protein TSC-22, TGFB-stimulated clone 22 homolog, Transforming growth factor beta-1-induced transcript 4 protein

All UniProt accessions (4): Q15714, C9IZ15, C9JYW3, H7C4J9

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. Acts on the C-type natriuretic peptide (CNP) promoter. Acts to promote CASP3-mediated apoptosis. Positively regulates TGF-beta signaling by interacting with SMAD7 which inhibits binding of SMAD7 to TGFBR1, preventing recruitment of SMURF ubiquitin ligases to TGFBR1 and inhibiting SMURF-mediated ubiquitination and degradation of TGFBR1. Contributes to enhancement of TGF-beta signaling by binding to and modulating the transcription activator activity of SMAD4. Promotes TGF-beta-induced transcription of COL1A2; via its interaction with TFE3 at E-boxes in the gene proximal promoter. Plays a role in the repression of hematopoietic precursor cell growth. Promotes IL2 deprivation-induced apoptosis in T-lymphocytes, via repression of TSC22D3/GILZ transcription and activation of the caspase cascade. May act to negatively regulate TGFB3 signaling and thereby inhibit cell death in mammary gland cells. Positively regulates cell death in response to TGFB3 during mammary gland involution.

Subunit / interactions. Forms homodimers. Forms heterodimers. Component of a complex composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1. Interacts with SMAD7; the interaction requires TGF-beta and the interaction is inhibited by TGFBR1. Interacts with TPT1/fortilin; interaction results in the destabilization of TSC22D1 protein and prevents TSC22D1-mediated apoptosis. Interacts with SMAD4 (via N-terminus). Interacts with ACVRL1/ALK1, ACVR1/ALK2, BMPR1A/ALK3, ACVR1B/ALK4, BMPR1B/ALK6, ACVR2A/ACTRII, and BMPR2. Interacts with SMAD6. Interacts with TFE3; the interaction is enhanced in the presence of TGF-beta. Forms a heterodimer with TSC22D4/THG1. Forms a heterodimer with TSC22D4/THG1. Interacts with histone H1-2. Interacts with GNL3. Interacts with histone H1-2.

Subcellular location. Cytoplasm. Nucleus. Cell membrane Cytoplasm. Mitochondrion Cytoplasm.

Tissue specificity. Ubiquitously expressed in adult tissues. Expressed in the postmitotic epithelial compartment at the top of intestinal mucosal villi.

Induction. Induced by cytokines including TGFB1 in aortic endothelial cells.

Similarity. Belongs to the TSC-22/Dip/Bun family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q15714-1	1, TSC22D1-1	yes
Q15714-2	2, TSC22D1-2, TSC-22
Q15714-3	3
Q15714-4	4
Q15714-5	5, TSC22D1-3, TSC22(86)

RefSeq proteins (4): NP_001230726, NP_001230727, NP_006013, NP_904358* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000580	TSC22/Bun	Family
IPR047862	TSC22/BUN_CS	Conserved_site

Pfam: PF01166

UniProt features (33 total): compositionally biased region 11, region of interest 9, splice variant 6, sequence conflict 4, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15714-F1	43.12	0.05

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 (1): 263

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2892245	POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation

MSigDB gene sets: 522 (showing top): RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, YAGI_AML_WITH_INV_16_TRANSLOCATION, KAAB_FAILED_HEART_ATRIUM_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, DITTMER_PTHLH_TARGETS_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, MEF2_02, GOBP_POSITIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS, EFC_Q6, GOBP_STEM_CELL_PROLIFERATION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, BILD_HRAS_ONCOGENIC_SIGNATURE, GTGCCTT_MIR506

GO Biological Process (10): regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), positive regulation of cell population proliferation (GO:0008284), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of programmed cell death (GO:0043068), negative regulation of programmed cell death (GO:0043069), negative regulation of hematopoietic stem cell proliferation (GO:1902034), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transcriptional regulation of pluripotent stem cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of DNA-templated transcription	2
DNA-templated transcription	2
positive regulation of cellular process	2
apoptotic process	2
regulation of apoptotic process	2
programmed cell death	2
regulation of programmed cell death	2
intracellular membrane-bounded organelle	2
cytoplasm	2
transcription by RNA polymerase II	1
cell population proliferation	1
regulation of cell population proliferation	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
negative regulation of cellular process	1
hematopoietic stem cell proliferation	1
regulation of hematopoietic stem cell proliferation	1
negative regulation of hemopoiesis	1
negative regulation of stem cell proliferation	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
protein binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSC22D1	LDLRAD4	O15165	720
TSC22D1	LHX4	Q969G2	604
TSC22D1	TGFB1	P01137	563
TSC22D1	LHX3	Q9UBR4	547
TSC22D1	SMAD4	Q13485	493
TSC22D1	MYC	P01106	493
TSC22D1	SLCO6A1	Q86UG4	428
TSC22D1	NRBP1	Q9UHY1	388
TSC22D1	TSC22D4	Q9Y3Q8	383
TSC22D1	TNFRSF1B	P20333	382
TSC22D1	PPP1R12B	O60237	381
TSC22D1	ANGPTL2	Q9UKU9	371
TSC22D1	ZNF157	P51786	357
TSC22D1	RNF31	Q96EP0	353
TSC22D1	MYLK	Q15746	353

IntAct

201 interactions, top by confidence:

A	B	Type	Score
NRBP1	TSC22D2	psi-mi:“MI:0914”(association)	0.730
TSC22D1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.670
NTAQ1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.670
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
TSC22D4	TSC22D2	psi-mi:“MI:0914”(association)	0.640
TSC22D1	TPT1	psi-mi:“MI:0407”(direct interaction)	0.590
TPT1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.590
TSC22D1	TPT1	psi-mi:“MI:0915”(physical association)	0.590
APLP1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.550
TSC22D1	CCDC90B	psi-mi:“MI:0915”(physical association)	0.550
SETDB1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.550
TSC22D1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.550
NRBP1	TBC1D4	psi-mi:“MI:0914”(association)	0.530
CACNA1A	TSC22D1	psi-mi:“MI:0915”(physical association)	0.370
TSC22D1	PTN	psi-mi:“MI:0915”(physical association)	0.370
TSC22D1	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CFTR	TSC22D1	psi-mi:“MI:0915”(physical association)	0.370
TSC22D1	A2M	psi-mi:“MI:0915”(physical association)	0.370
TSC22D1	ERG28	psi-mi:“MI:0915”(physical association)	0.370
LRIF1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.370
TSC22D1	SPACA9	psi-mi:“MI:0915”(physical association)	0.370
CARHSP1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.370
CHD3	TSC22D1	psi-mi:“MI:0915”(physical association)	0.370
TSC22D1	CRMP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (128): WDYHV1 (Two-hybrid), TSC22D1 (Affinity Capture-MS), TSC22D1 (Affinity Capture-MS), TSC22D1 (Affinity Capture-MS), TSC22D1 (Affinity Capture-RNA), TSC22D1 (Affinity Capture-MS), TSC22D1 (Affinity Capture-MS), TSC22D1 (Affinity Capture-MS), TSC22D1 (Affinity Capture-RNA), GSTK1 (Affinity Capture-MS), DYNC1H1 (Affinity Capture-MS), EPPK1 (Affinity Capture-MS), BAG6 (Affinity Capture-MS), MTR (Affinity Capture-MS), DNAAF5 (Affinity Capture-MS)

ESM2 similar proteins: B2C6R6, B2RWS6, B7SBD2, F4I171, O15405, O15409, P0CF24, P32257, P39769, P45481, P47825, P58463, Q09472, Q14686, Q15714, Q172Y1, Q17BA4, Q29A33, Q29DV9, Q4R4H5, Q4V3C1, Q4X0N1, Q52JK6, Q59QW5, Q5QL03, Q5R4H1, Q60YF6, Q6JHU9, Q6NS15, Q7XYY2, Q7ZVN7, Q80W03, Q86NP2, Q8HZ00, Q8IZL2, Q8MJ97, Q8MJ98, Q8MJ99, Q8MJA0, Q8SWR8

Diamond homologs: E9Q7M2, O75157, P62500, P62501, P80220, Q15714, Q22544, Q24522, Q24523, Q27I66, Q3B8N7, Q3MHL6, Q4R4H5, Q5R4H1, Q5RED5, Q99576, Q9EQN3, Q9EQZ1, Q9Y3Q8, Q9Z2S7, Q91012

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TSC22D1	“up-regulates quantity by expression”	NPPC	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Recognition of DNA damage by PCNA-containing replication complex	5	15.7×	3e-03
HSF1 activation	5	15.7×	3e-03
Activation of ATR in response to replication stress	5	12.4×	5e-03
Dual Incision in GG-NER	5	10.7×	6e-03
Vif-mediated degradation of APOBEC3G	5	10.5×	6e-03
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	6	9.8×	5e-03
Gap-filling DNA repair synthesis and ligation in TC-NER	6	8.8×	5e-03
Dual incision in TC-NER	6	8.6×	5e-03

Disease & clinical

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	11
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

288 predictions. Top by Δscore:

Variant	Effect	Δscore
13:44434879:AGATC:A	acceptor_gain	1.0000
13:44434880:GATC:G	acceptor_gain	1.0000
13:44434881:ATC:A	acceptor_gain	1.0000
13:44434882:TC:T	acceptor_gain	1.0000
13:44434883:CC:C	acceptor_gain	1.0000
13:44434884:C:CC	acceptor_gain	1.0000
13:44434885:T:A	acceptor_loss	1.0000
13:44436764:G:C	donor_gain	1.0000
13:44434884:C:T	acceptor_gain	0.9900
13:44436040:ATACC:A	donor_loss	0.9900
13:44436041:TAC:T	donor_loss	0.9900
13:44436042:A:AC	donor_gain	0.9900
13:44436042:A:T	donor_loss	0.9900
13:44436043:C:CC	donor_gain	0.9900
13:44436043:C:G	donor_loss	0.9900
13:44436048:G:C	donor_gain	0.9900
13:44436092:GGAG:G	acceptor_gain	0.9900
13:44436095:GCTGA:G	acceptor_loss	0.9900
13:44436096:C:CC	acceptor_gain	0.9900
13:44436096:C:T	acceptor_loss	0.9900
13:44436097:T:A	acceptor_loss	0.9900
13:44436767:T:TA	donor_gain	0.9900
13:44435763:C:A	donor_gain	0.9800
13:44436038:ACAT:A	donor_loss	0.9800
13:44436093:GAG:G	acceptor_gain	0.9800
13:44436822:T:TA	donor_gain	0.9800
13:44436823:C:A	donor_gain	0.9800
13:44436094:AG:A	acceptor_gain	0.9700
13:44434881:ATCC:A	acceptor_gain	0.9600
13:44434882:TCCT:T	acceptor_gain	0.9600

AlphaMissense

6974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:44434759:A:G	L1030P	1.000
13:44434768:A:G	L1027P	1.000
13:44434768:A:T	L1027Q	1.000
13:44434771:A:G	L1026P	1.000
13:44434789:A:G	L1020P	1.000
13:44434810:A:G	L1013P	1.000
13:44434822:T:G	Q1009P	1.000
13:44434828:T:A	K1007I	1.000
13:44434831:A:G	L1006P	1.000
13:44434831:A:T	L1006H	1.000
13:44434852:A:T	V999D	1.000
13:44434856:C:G	A998P	1.000
13:44434861:A:G	M996T	1.000
13:44434863:C:A	L995F	1.000
13:44434863:C:G	L995F	1.000
13:44434864:A:C	L995W	1.000
13:44434864:A:G	L995S	1.000
13:44434866:A:C	H994Q	1.000
13:44434866:A:T	H994Q	1.000
13:44434867:T:G	H994P	1.000
13:44434868:G:C	H994D	1.000
13:44434872:T:A	K992N	1.000
13:44434872:T:G	K992N	1.000
13:44434873:T:A	K992I	1.000
13:44434874:T:C	K992E	1.000
13:44434874:T:G	K992Q	1.000
13:44434876:A:G	V991A	1.000
13:44434876:A:T	V991E	1.000
13:44434877:C:T	V991M	1.000
13:44434879:A:G	L990P	1.000

dbSNP variants (sampled 300 via entrez): RS1000050699 (13:44515828 G>A), RS1000073894 (13:44576964 A>C), RS1000078305 (13:44483705 C>T), RS1000078660 (13:44518775 T>C), RS1000082332 (13:44559366 T>C), RS1000130601 (13:44444077 A>C,G), RS1000145895 (13:44568408 G>C), RS1000177929 (13:44532476 C>A,T), RS1000189789 (13:44435046 T>A,C), RS1000203173 (13:44432256 GA>G), RS1000230397 (13:44461905 C>T), RS1000253331 (13:44553188 A>T), RS1000282065 (13:44444036 C>T), RS1000297526 (13:44458355 C>T), RS1000369000 (13:44441081 G>A)

Disease associations

OMIM: gene MIM:607715 | 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
GCST001613_14	Antineutrophil cytoplasmic antibody-associated vasculitis	3.000000e-06
GCST002805_11	Body mass index	7.000000e-06
GCST005790_27	Rosacea symptom severity	5.000000e-06
GCST010002_185	Refractive error	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement
EFO:0009180	rosacea severity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	6
bisphenol A	decreases expression, increases expression, affects methylation, affects cotreatment, increases methylation	3
trichostatin A	affects cotreatment, decreases expression, affects expression	3
Cisplatin	increases expression, affects cotreatment, decreases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Asbestos, Crocidolite	increases expression	2
Cadmium Chloride	affects expression, decreases expression	2
Genistein	increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
arsenite	increases methylation	1
o,p’-DDT	decreases expression	1
afimoxifene	decreases reaction, decreases expression	1
sodium arsenite	increases expression	1
bleomycetin	increases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
pinosylvin	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
archazolid B	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
jinfukang	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XD01	HCT116-Cas9-TSC22KO-569	Cancer cell line	Male

Clinical trials (associated diseases)

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