ID1

Summary

ID1 (inhibitor of DNA binding 1, HGNC:5360) is a protein-coding gene on chromosome 20q11.21, encoding DNA-binding protein inhibitor ID-1 (P41134). Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity.

The protein encoded by this gene is a helix-loop-helix (HLH) protein that can form heterodimers with members of the basic HLH family of transcription factors. The encoded protein has no DNA binding activity and therefore can inhibit the DNA binding and transcriptional activation ability of basic HLH proteins with which it interacts. This protein may play a role in cell growth, senescence, and differentiation. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3397 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• Transcription factor: yes — 88 downstream targets (CollecTRI)
• MANE Select transcript: NM_002165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5360
Approved symbol	ID1
Name	inhibitor of DNA binding 1
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ857M17.1.2, bHLHb24
Ensembl gene	ENSG00000125968
Ensembl biotype	protein_coding
OMIM	600349
Entrez	3397

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000376105, ENST00000376112, ENST00000718307, ENST00000718308, ENST00000903277, ENST00000903278, ENST00000903279, ENST00000903280, ENST00000972141

RefSeq mRNA: 2 — MANE Select: NM_002165 NM_002165, NM_181353

CCDS: CCDS13185, CCDS13186

Canonical transcript exons

ENST00000376112 — 2 exons

Exon	Start	End
ENSE00001469404	31606053	31606510
ENSE00004034728	31605289	31605813

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 158.1885 / max 1949.2361, expressed in 1645 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183975	158.1885	1645

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	99.51	gold quality
right lung	UBERON:0002167	99.23	gold quality
right lobe of thyroid gland	UBERON:0001119	99.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.00	gold quality
left lobe of thyroid gland	UBERON:0001120	98.98	gold quality
left uterine tube	UBERON:0001303	98.90	gold quality
cauda epididymis	UBERON:0004360	98.84	gold quality
mucosa of stomach	UBERON:0001199	98.79	gold quality
mucosa of transverse colon	UBERON:0004991	98.79	gold quality
apex of heart	UBERON:0002098	98.78	gold quality
pharyngeal mucosa	UBERON:0000355	98.67	gold quality
heart right ventricle	UBERON:0002080	98.45	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.43	gold quality
colonic mucosa	UBERON:0000317	98.40	gold quality
nasal cavity mucosa	UBERON:0001826	98.35	gold quality
upper leg skin	UBERON:0004262	98.35	gold quality
thyroid gland	UBERON:0002046	98.27	gold quality
right atrium auricular region	UBERON:0006631	98.21	gold quality
cardiac atrium	UBERON:0002081	98.09	gold quality
esophagus mucosa	UBERON:0002469	98.06	gold quality
lower lobe of lung	UBERON:0008949	98.03	gold quality
urethra	UBERON:0000057	98.00	gold quality
adenohypophysis	UBERON:0002196	98.00	gold quality
cartilage tissue	UBERON:0002418	97.88	gold quality
upper lobe of left lung	UBERON:0008952	97.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.83	gold quality
upper lobe of lung	UBERON:0008948	97.80	gold quality
esophagus	UBERON:0001043	97.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.78	gold quality
lower esophagus	UBERON:0013473	97.77	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	3682.90
E-HCAD-9	yes	2750.91
E-MTAB-7052	yes	2500.37
E-MTAB-8205	yes	2449.82
E-GEOD-134144	yes	2203.58
E-GEOD-76312	yes	547.01
E-HCAD-1	yes	267.22
E-MTAB-6701	yes	75.24
E-MTAB-10287	yes	70.82
E-MTAB-10553	yes	60.58
E-HCAD-10	yes	36.40
E-HCAD-5	yes	31.67
E-CURD-46	yes	31.47
E-MTAB-8410	yes	29.78
E-GEOD-125970	yes	23.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

88 targets.

Target	Regulation
ADD1
AHSG
ALPL
ASCL1
AURKA	Activation
BGLAP
BMI1	Unknown
BMP4
BRCA1	Repression
CCND1	Repression
CCND3
CD44
CD79A
CD8A
CDH1	Repression
CDH17
CDK6
CDKN1A	Activation
CDKN1B
CDKN2A	Activation
CDKN2B
CKM	Repression
CTNNB1	Activation
CTSK	Repression
DELEC1
DLST
DTX1
EGFR
EIF3K
EPOR

Upstream regulators (CollecTRI, top): ACVRL1, ATF3, ATF5, BHLHE40, BMP2, BMP6, BMPR1A, CDH5, CEBPA, CREB1, DDIT3, EGR1, FLT3, FOXO1, FOXO3, GDF2, GDF5, GDNF, HAMP, HAND2, HEY1, ID1, ID2, LYL1, MYC, NSD2, POU2F1, SMAD1, SMAD3, SMAD4, SMAD5, SMAD9, SP1, SSRP1, STAT5A, TCF3, TGFB1I1, TP53, TRIM28, ZBTB18

miRNA regulators (miRDB)

43 targeting ID1, 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-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-1277-5P	100.00	73.95	5056
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-654-3P	98.38	67.61	905

Literature-anchored findings (GeneRIF, showing 40)

• Id1, a dominant negative inhibitor of basic helix-loop-helix proteins, is a direct target gene for BMP (PMID:11729207)
• Id-1 expression is linked with the loss of NF-1/Rb/HDAC-1 transcription repressor complex in metastatic breast cancer (PMID:11896613)
• role in stimulating serum-independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway (PMID:12016143)
• TGF beta 1 may be one of the upstream regulators of Id-1 (PMID:12020803)
• immunohistochemical studies on NPC samples showed that expression of Id-1 was present in NPC cells but absent in normal tissues. This study demonstrates that Id-1 plays an important role in cell proliferation in NPC cells (PMID:12203366)
• Data suggest that signalling of BMP-2 to stimulate the expression of Id1 would be transduced by BMPR-IA and mediated by Smad1 and Smad4. (PMID:12296825)
• Level of protein expression correlates with poor differentiation, enhanced malignant potential, and more aggressive clinical behavior of epithelial ovarian tumors. (PMID:12576450)
• expression in human endothelial cells induced by Kaposi sarcoma-associated herpesvirus LANA protein, expression in Kaposi sarcoma tumor cells and in vivo (PMID:12719589)
• expression may relate to the metastatic behaviour in human oral squamous cell carcinoma (PMID:12787042)
• dysregulated Id-1 may not only contribute to delaying the senescence program in keratinocytes, it may also contribute to the escape of the relatively undifferentiated tumor cells in BCC from immune surveillance. (PMID:12823438)
• Our results strongly suggest that Id-1 may be one of the upstream regulators of NF-kappaB and activation of NF-kappaB signalling pathway may be essential for Id-1 induced cell proliferation through protection against apoptosis. (PMID:12881706)
• Significantly overexpressed in papillary thyroid cancer. Primarily localized to cytoplasm of thyroid follicular cells. Activation of the mitogen intracellular protein kinase A and protein kinase C signaling pathways up-regulated Id-1 mRNA expression. (PMID:12947323)
• over-expression of Id-1 induces cell proliferation in HCC through inactivation of p16INK4a/retinoblastoma pathway (PMID:12949053)
• Expression of Id-1 was able to reduce androgen-stimulated growth and S phase fraction of the cell cycle in prostatic cancer cells. (PMID:14688027)
• Id1 protein is involved in the process of differentiation of keratinocytes seeen in normal skin and Id1 pathway is activated in psoriasis. (PMID:14690332)
• Id-1 may be an upstream regulator of the Raf/MEK signalling pathway, which plays an essential role in protection against taxol-induced apoptosis (PMID:14742319)
• ID1 may contribute to oncogenesis not only by inhibiting transcriptional activity of basic helix-loop-helix transcription factors and abrogate differentiation but also by subverting centrosome duplication. (PMID:14755252)
• ID-1 expression significantly associated with intratumoral microvessel density in pancreatic cancer (PMID:15026801)
• Id-1 and Id-2 proteins control prostate cancer cell phenotypes and could serve as molecular markers of aggressive human prostate cancer. (PMID:15041724)
• Id1 induction by LMP1 depends on its NF-kappaB activation domain at the COOH-terminal region, CTAR1 and CTAR2. This may facilitate clonal expansion of premalignant nasopharyngeal epithelial cells infected with EBV & promote malignant transformation. (PMID:15064751)
• silencing Id1 expression in young cells by RNA interference induced an increased p16(INK4a) level and premature cellular senescence (PMID:15138269)
• MyoD modulates the rate of Id1 degradation and suggest a dynamic interplay of these factors (PMID:15163661)
• induction of Id1 not only blocks transcriptional activity but also induces myogenin degradation by blocking formation of myogenin-E47 protein complexes. (PMID:15322112)
• Id1 can be up-regulated and p53 down-regulated by a statin in endothelial cells. Regulation of these proteins in endothelial cells may account for the proangiogenic effect of statins. (PMID:15370294)
• Id1 has cell cycle regulatory functions that are similar to those of c-Myc. (PMID:15489884)
• Overexpression of Id1 enhances expression of ICAM-1 and E-selectin, and induces angiogenic processes such as transmigration, matrix metalloproteinase-2 and -9 expression, and tube formation in cultured vascular endothelial cells. (PMID:15494533)
• Idl protein may play an important role in the process of gastric carcinogenesis, and high-level Id I expression may be related to the malignant potential of tumor cells (PMID:15575081)
• Id1 is overexpressed in hyperplastic and neoplastic thyroid tissue and directly regulates the growth of thyroid cancer cells of follicular cell origin, but is not a marker of aggressive phenotype in differentiated thyroid cancer. (PMID:15579766)
• Id1, 2 and 3 might play a role in the early stages of hepatocarcinogenesis, but not in the development of advanced carcinoma, and might consequently be related to HCC dedifferentiation (PMID:15645115)
• Thus, we speculate that the regulation of cell growth mediated by CASK may be involved in Id1. (PMID:15694377)
• constitutive expression of Id1 inhibits eosinophil development, whereas in contrast neutrophil differentiation was modestly enhanced (PMID:15701714)
• These results indicate ID1 and ID2 are important retinoic acid responsive genes in acute promyelocytic leukemia [APL], and suggest that inhibition of specific bHLH transcription factor complexes may play a role in the therapeutic effect of ATRA in APL (PMID:15744343)
• In mature human B cells, BMP-6 inhibited cell growth, and rapidly induced an upregulation of Id1. (PMID:15877825)
• Downregulation of Id-1 may be a novel target to inhibit the growth of metastatic cancers through the suppression of angiogenesis. (PMID:15905202)
• Furthermore, by using DCs derived from Id1(-/-) mice that are defective in Flt-1 signaling, we demonstrated that the inhibitory function of VEGF on DC function is most likely mediated by Flt-1. (PMID:16002046)
• degradation is modulated by E12 and E47 (PMID:16007194)
• Id1 gene expression may be associated with thyroid cancer cell growth and differentiation. (PMID:16029118)
• Expression of Id1 in HM was significantly higher than that in normal placenta. (PMID:16115231)
• Id-1 protein may be regulated by TNFalpha through the ubiquitin/proteasome degradation pathway and the stability of the Id-1 protein appears to correlate with the sensitivity of TNFalpha-induced apoptosis (PMID:16123120)
• study supports a significant role of the ID1 protein in melanoma progression and patient prognosis; inverse relation between ID1 and TSP-1 expression support an important role of ID1 in regulation of this complex multitarget protein. (PMID:16189525)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	id1	ENSDARG00000040764
mus_musculus	Id1	ENSMUSG00000042745
rattus_norvegicus	Id1	ENSRNOG00000021750
drosophila_melanogaster	emc	FBGN0000575

Paralogs (3): ID2 (ENSG00000115738), ID3 (ENSG00000117318), ID4 (ENSG00000172201)

Protein

Protein identifiers

DNA-binding protein inhibitor ID-1 — P41134 (reviewed: P41134)

Alternative names: Class B basic helix-loop-helix protein 24, Inhibitor of DNA binding 1, Inhibitor of differentiation 1

All UniProt accessions (1): P41134

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Inhibits skeletal muscle and cardiac myocyte differentiation. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer.

Subunit / interactions. Heterodimer with other HLH proteins. Interacts with COPS5, IFI204, GATA4 and NKX2-5. Interacts with CLOCK and BMAL1.

Subcellular location. Cytoplasm. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
P41134-1	ID-A	yes
P41134-2	ID-B

RefSeq proteins (2): NP_002156, NP_851998 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR026052	DNA-bd_prot-inh	Family
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00010

UniProt features (8 total): sequence conflict 3, chain 1, domain 1, short sequence motif 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41134-F1	67.59	0.25

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity

MSigDB gene sets: 453 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CIRCADIAN_RHYTHM, ATF_B, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, HNF3ALPHA_Q6, AMIT_DELAYED_EARLY_GENES, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GCANCTGNY_MYOD_Q6, BECKER_TAMOXIFEN_RESISTANCE_UP, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1

GO Biological Process (28): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), endothelial cell morphogenesis (GO:0001886), transforming growth factor beta receptor signaling pathway (GO:0007179), heart development (GO:0007507), circadian rhythm (GO:0007623), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), neuron differentiation (GO:0030182), BMP signaling pathway (GO:0030509), protein destabilization (GO:0031648), collagen metabolic process (GO:0032963), regulation of MAPK cascade (GO:0043408), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), blood vessel endothelial cell migration (GO:0043534), negative regulation of osteoblast differentiation (GO:0045668), regulation of angiogenesis (GO:0045765), negative regulation of DNA-templated transcription (GO:0045892), response to antibiotic (GO:0046677), blood vessel morphogenesis (GO:0048514), lung morphogenesis (GO:0060425), lung vasculature development (GO:0060426), endothelial cell apoptotic process (GO:0072577), negative regulation of cold-induced thermogenesis (GO:0120163), negative regulation of endothelial cell apoptotic process (GO:2000352), apoptotic process (GO:0006915), obsolete negative regulation of transcription by transcription factor localization (GO:0010621), rhythmic process (GO:0048511)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), protein dimerization activity (GO:0046983), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular Senescence	1
Nuclear Events (kinase and transcription factor activation)	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	3
negative regulation of DNA-templated transcription	2
transforming growth factor beta receptor superfamily signaling pathway	2
gene expression	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell development	1
epithelial cell morphogenesis	1
cellular response to transforming growth factor beta stimulus	1
animal organ development	1
circulatory system development	1
rhythmic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
cell differentiation	1
generation of neurons	1
cellular response to BMP stimulus	1
regulation of protein stability	1
metabolic process	1
MAPK cascade	1
regulation of intracellular signal transduction	1
endothelial cell migration	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
response to chemical	1
blood vessel development	1
tube morphogenesis	1
transcription coregulator activity	1
protein binding	1
transcription regulator activity	1

Protein interactions and networks

STRING

1966 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ID1	FOXO3	O43524	989
ID1	KLF17	Q5JT82	771
ID1	HEY1	Q9Y5J3	759
ID1	TCF4	P15884	759
ID1	TCF3	P15883	739
ID1	ID4	P47928	714
ID1	EBF2	Q9HAK2	694
ID1	MYOD1	P15172	693
ID1	CDKN2A	P42771	630
ID1	MYC	P01106	628
ID1	BMPR2	Q13873	592
ID1	BMP4	P12644	588
ID1	ETS2	P15036	588
ID1	BMP2	P12643	587
ID1	GDF2	Q9UK05	587

IntAct

74 interactions, top by confidence:

A	B	Type	Score
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
TCF4	ID1	psi-mi:“MI:0915”(physical association)	0.660
ID1	CAV1	psi-mi:“MI:0915”(physical association)	0.600
CAV1	ID1	psi-mi:“MI:0915”(physical association)	0.600
ID1	CAV1	psi-mi:“MI:0403”(colocalization)	0.600
MYOG	ID1	psi-mi:“MI:0915”(physical association)	0.600
ID1	TCF12	psi-mi:“MI:0915”(physical association)	0.560
TCF3	ID1	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ID1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	ID1	psi-mi:“MI:0915”(physical association)	0.560
ID1	ASCL3	psi-mi:“MI:0915”(physical association)	0.560
TCF4	ID1	psi-mi:“MI:0915”(physical association)	0.560
CHAT	ID1	psi-mi:“MI:0915”(physical association)	0.560
ID1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
ID1	GSN	psi-mi:“MI:0915”(physical association)	0.560
ID1		psi-mi:“MI:0915”(physical association)	0.560
ID1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (110): ID1 (Affinity Capture-Western), ID1 (Two-hybrid), COL12A1 (Affinity Capture-MS), MPP1 (Affinity Capture-MS), PSMD5 (Affinity Capture-MS), DPF2 (Affinity Capture-MS), STXBP1 (Affinity Capture-MS), TCF3 (Affinity Capture-MS), TCF12 (Affinity Capture-MS), PIAS1 (Affinity Capture-MS), MKNK1 (Affinity Capture-MS), BUD31 (Affinity Capture-MS), CHD1L (Affinity Capture-MS), USP15 (Affinity Capture-MS), TXNL4A (Affinity Capture-MS)

ESM2 similar proteins: A6NI87, O60682, O88940, P0C282, P0DH66, P20067, P41133, P41134, P41135, P41136, P41137, P41138, P41139, P47928, P59101, P70562, P79782, Q02363, Q02535, Q06AV5, Q2VIU1, Q3ZC46, Q4R5J7, Q5E981, Q5EAE9, Q5RCH7, Q5RJB0, Q60539, Q60756, Q66J78, Q688C4, Q6EPZ2, Q6GL62, Q6H509, Q6IEK5, Q6J1A5, Q6PBD7, Q6Q2A8, Q6REU5, Q6SW81

Diamond homologs: P18491, P20067, P41133, P41134, P41135, P41136, P41137, P41138, P41139, P47928, Q02363, Q02535, Q06AV5, Q2VIU1, Q3ZC46, Q4R5J7, Q5E981, Q5RCH7, Q66J78, Q688C4, Q6GL62, Q6PBD7, Q712G9, Q7SZ28, Q7ZXF3, Q91399, Q9PWJ5, O73823, O93507, P17542, P22091, P24899, Q6QHK4, O73615, O96004, P57100, P97832, Q0VCE2, Q28555, Q64279

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
ID1	unknown	CASK	binding
GDF5	“up-regulates quantity by expression”	ID1	“transcriptional regulation”
ID1	up-regulates	AKT1	binding
PML-RARalpha	“up-regulates quantity by expression”	ID1	“transcriptional regulation”
NFY	“up-regulates quantity by expression”	ID1	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	ID1	“transcriptional regulation”
ID1	up-regulates	AKT	binding
CAMK2A	“up-regulates activity”	ID1	phosphorylation
ID1	“down-regulates activity”	MYOD1	binding
ID1	“down-regulates activity”	TCF12	binding
ID1	“down-regulates activity”	TCF3	binding
ID1	“down-regulates activity”	MYOD/HEB	binding
ID1	“down-regulates activity”	MYOD/E2-2	binding
ID1	“down-regulates activity”	MYOD/E12E47	binding
ID1	“down-regulates activity”	TCF4	binding
FLT3	“up-regulates quantity by expression”	ID1	“transcriptional regulation”
GDNF	“up-regulates quantity by expression”	ID1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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
TGFBR3 expression	5	81.6×	1e-06
Myogenesis	5	68.0×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

144 predictions. Top by Δscore:

Variant	Effect	Δscore
20:31605810:CGAGG:C	donor_loss	0.9900
20:31605811:GAGG:G	donor_loss	0.9900
20:31605813:GGTG:G	donor_loss	0.9900
20:31605814:G:T	donor_loss	0.9900
20:31605815:T:A	donor_loss	0.9900
20:31606047:TCACA:T	acceptor_loss	0.9800
20:31606050:CA:C	acceptor_loss	0.9800
20:31606051:A:AG	acceptor_gain	0.9800
20:31606051:A:C	acceptor_loss	0.9800
20:31606051:AGGC:A	acceptor_gain	0.9800
20:31606051:AGGCG:A	acceptor_gain	0.9800
20:31606052:G:GG	acceptor_gain	0.9800
20:31606052:GGC:G	acceptor_gain	0.9800
20:31606052:GGCG:G	acceptor_gain	0.9800
20:31606052:GGCGG:G	acceptor_gain	0.9800
20:31605876:G:GT	donor_gain	0.9700
20:31606050:C:G	acceptor_gain	0.9700
20:31605814:G:GG	donor_gain	0.9600
20:31605811:GAG:G	donor_gain	0.9500
20:31606042:C:CA	acceptor_gain	0.9500
20:31606049:A:AG	acceptor_gain	0.9400
20:31606051:AG:A	acceptor_gain	0.9400
20:31606052:GG:G	acceptor_gain	0.9400
20:31605875:GGGC:G	donor_gain	0.9200
20:31606049:ACAG:A	acceptor_gain	0.9200
20:31605933:GTGCC:G	donor_gain	0.8900
20:31605934:TGCCT:T	donor_gain	0.8900
20:31605868:C:T	donor_gain	0.8300
20:31605727:G:GT	donor_gain	0.8100
20:31605825:A:G	donor_gain	0.8100

AlphaMissense

983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:31605614:T:A	L76H	1.000
20:31605614:T:C	L76P	1.000
20:31605623:T:C	L79P	1.000
20:31605671:T:A	L95H	1.000
20:31605671:T:C	L95P	1.000
20:31605701:T:C	L105P	1.000
20:31605656:G:T	S90I	0.999
20:31605677:A:C	H97P	0.999
20:31605680:T:A	V98D	0.999
20:31605692:T:A	I102N	0.999
20:31605692:T:C	I102T	0.999
20:31605701:T:A	L105H	0.999
20:31605604:T:G	Y73D	0.998
20:31605614:T:G	L76R	0.998
20:31605668:T:G	I94S	0.998
20:31605674:A:C	Q96P	0.998
20:31605683:T:A	I99N	0.998
20:31605692:T:G	I102S	0.998
20:31605713:T:C	L109P	0.998
20:31605601:T:C	C72R	0.997
20:31605604:T:C	Y73H	0.997
20:31605613:C:T	L76F	0.997
20:31605668:T:C	I94T	0.997
20:31605671:T:G	L95R	0.997
20:31605683:T:G	I99S	0.997
20:31605688:T:C	Y101H	0.997
20:31605590:A:T	D68V	0.996
20:31605625:G:A	V80M	0.996
20:31605679:G:C	V98L	0.996
20:31605689:A:G	Y101C	0.996

dbSNP variants (sampled 300 via entrez): RS1000147063 (20:31606366 A>G,T), RS1000215198 (20:31605492 G>C), RS1002226519 (20:31606951 G>A), RS1002325758 (20:31603841 G>A,C,T), RS1002495331 (20:31606816 C>A,T), RS1004341983 (20:31605288 C>A,G,T), RS1006186167 (20:31603965 ATTAT>A), RS1006214833 (20:31606468 G>A), RS1006330079 (20:31603378 T>C), RS1006462726 (20:31603500 C>A,T), RS1006663715 (20:31604267 G>A,C,T), RS1006679227 (20:31606684 A>G), RS1006799350 (20:31604410 G>A), RS1006976791 (20:31604601 G>A), RS1008336107 (20:31604981 A>T)

Disease associations

OMIM: gene MIM:600349 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007094_233	Diastolic blood pressure	7.000000e-13
GCST007099_191	Systolic blood pressure	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075116 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression, increases reaction	7
Tretinoin	decreases reaction, increases expression	7
Valproic Acid	increases expression	5
Benzo(a)pyrene	decreases expression, increases expression	4
Aflatoxin B1	affects expression, increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	increases expression, decreases expression	3
Arsenic Trioxide	decreases response to substance, decreases expression, increases expression, decreases reaction	3
Air Pollutants	decreases expression, increases abundance	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Silicon Dioxide	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects cotreatment	3
Cyclosporine	decreases expression	3
Genistein	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
sulindac sulfide	decreases expression	2
mercuric bromide	affects cotreatment, increases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
(+)-JQ1 compound	increases expression	2
Resveratrol	decreases expression, decreases reaction, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Cisplatin	affects cotreatment, increases expression	2
Dexamethasone	decreases expression, affects cotreatment, increases expression	2
Doxorubicin	increases expression	2
Folic Acid	affects expression, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
Hydrogen Peroxide	affects expression, decreases expression	2
Lipopolysaccharides	decreases reaction, affects response to substance, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Polystyrenes	decreases expression, increases abundance	2

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1099689	Binding	Inhibition of ID1-protein in HSMC assessed as increase in alpha-actin protein level by Western blotting	Synthetic peptides containing a conserved sequence motif of the Id protein family modulate vascular smooth muscle cell phenotype. — Bioorg Med Chem Lett

Cellosaurus cell lines

33 cell lines: 24 transformed cell line, 5 embryonic stem cell, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3C9	SEES3-1V human ID1, clone1	Embryonic stem cell	Male
CVCL_A3D0	SEES3-1V human ID1, clone2	Embryonic stem cell	Male
CVCL_A3D1	SEES3-1V human ID1, clone3	Embryonic stem cell	Male
CVCL_B7TU	e-hChon-1	Transformed cell line	Female
CVCL_B7TV	e-hChon-2	Transformed cell line	Female
CVCL_B7U0	e-hDFib3	Transformed cell line	Male
CVCL_B7U3	e-hFib-3	Transformed cell line	Male
CVCL_B7U4	e-hLEC-1	Transformed cell line
CVCL_B7U5	e-hLEC-2	Transformed cell line
CVCL_B7U6	e-hMEC-1	Transformed cell line

Clinical trials (associated diseases)

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