ID4

Summary

ID4 (inhibitor of DNA binding 4, HGNC:5363) is a protein-coding gene on chromosome 6p22.3, encoding DNA-binding protein inhibitor ID-4 (P47928). 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.

This gene encodes a member of the inhibitor of DNA binding (ID) protein family. The encoded protein lacks DNA binding ability, and instead regulates gene expression through binding to and inhibiting basic helix-loop-helix transcription factors. This protein has been implicated in the regulation of diverse cellular processes that play a role in development and tumorigenesis.

Source: NCBI Gene 3400 — RefSeq curated summary.

At a glance

• GWAS associations: 32
• Clinical variants (ClinVar): 42 total
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_001546

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5363
Approved symbol	ID4
Name	inhibitor of DNA binding 4
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	bHLHb27
Ensembl gene	ENSG00000172201
Ensembl biotype	protein_coding
OMIM	600581
Entrez	3400

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000378700, ENST00000867159

RefSeq mRNA: 1 — MANE Select: NM_001546 NM_001546

CCDS: CCDS4544

Canonical transcript exons

ENST00000378700 — 3 exons

Exon	Start	End
ENSE00001148534	19838584	19838642
ENSE00001478452	19839210	19842197
ENSE00001478464	19837370	19838195

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.4597 / max 742.4748, expressed in 1142 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66233	32.9330	1122
66234	0.3505	144
66235	0.1026	38
66237	0.0527	19
66232	0.0208	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.58	gold quality
skin of hip	UBERON:0001554	99.41	gold quality
upper leg skin	UBERON:0004262	99.34	gold quality
ventricular zone	UBERON:0003053	99.19	gold quality
germinal epithelium of ovary	UBERON:0001304	99.05	gold quality
cranial nerve II	UBERON:0000941	98.95	gold quality
hair follicle	UBERON:0002073	98.88	gold quality
urethra	UBERON:0000057	98.67	gold quality
thyroid gland	UBERON:0002046	98.50	gold quality
seminal vesicle	UBERON:0000998	98.47	gold quality
left lobe of thyroid gland	UBERON:0001120	98.47	gold quality
parietal pleura	UBERON:0002400	98.45	gold quality
right lobe of thyroid gland	UBERON:0001119	98.44	gold quality
saphenous vein	UBERON:0007318	98.20	gold quality
right coronary artery	UBERON:0001625	98.15	gold quality
pleura	UBERON:0000977	98.11	gold quality
parotid gland	UBERON:0001831	98.11	gold quality
coronary artery	UBERON:0001621	97.99	gold quality
left coronary artery	UBERON:0001626	97.95	gold quality
superficial temporal artery	UBERON:0001614	97.87	gold quality
right uterine tube	UBERON:0001302	97.82	gold quality
epithelium of mammary gland	UBERON:0003244	97.78	gold quality
mammary duct	UBERON:0001765	97.77	gold quality
tibial artery	UBERON:0007610	97.73	gold quality
popliteal artery	UBERON:0002250	97.72	gold quality
upper arm skin	UBERON:0004263	97.62	gold quality
decidua	UBERON:0002450	97.59	gold quality
vena cava	UBERON:0004087	97.54	gold quality
visceral pleura	UBERON:0002401	97.53	gold quality
ganglionic eminence	UBERON:0004023	97.42	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	1851.71
E-MTAB-10485	yes	1309.24
E-MTAB-9435	yes	999.67
E-CURD-126	yes	925.41
E-HCAD-5	yes	44.04
E-GEOD-135922	yes	33.66
E-GEOD-137537	yes	32.95
E-MTAB-10287	yes	32.36
E-HCAD-10	yes	27.71
E-GEOD-84465	yes	24.51
E-MTAB-5061	yes	14.47
E-GEOD-93593	yes	13.56
E-MTAB-8271	yes	8.56
E-GEOD-81608	yes	8.06
E-ENAD-27	yes	4.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets.

Target	Regulation
ABCC3
ABCC6	Activation
BRCA1	Repression
CD74
CREBBP
CSN2
GFAP
ID4
IGF1R
IGFBP3
MBP
MIR335
PRH1
SOX2	Unknown
TFF1
TP53
TUBB3

Upstream regulators (CollecTRI, top): E2F1, GLI1, ID4, PAX3, PGR, SP1, SP3, TBXT, TP53, USF1, ZBTB18

miRNA regulators (miRDB)

191 targeting ID4, 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-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
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-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 40)

• A B-cell lineage acute lymphoblastic leukemia patient with a t(6;14)chromosomal translocation that deregulated ID4. (PMID:12969807)
• ID4 is downregulated by promoter hypermethylation in gastric adenocarcinoma. (PMID:14534543)
• ID4 gene is a potential tumor suppressor gene for which methylation status may play an important role in the CRC progression (PMID:15569977)
• identified Idb4 as a putative tumor-suppressor gene that is methylated in most mouse and human leukemias but in only a minority of other human cancers (PMID:15723065)
• effect of amplifications at 6p22.3 in bladder cancer is expected to be non-uniform, thereby contributing to the highly variable biological and clinical behavior of advanced stage tumors (PMID:15876350)
• ID proteins (ID1, ID2, ID3 and ID4) were significantly increased in Mecp2-deficient Rett syndrome brain; ID genes are ideal targets for MeCP2 regulation of neuronal maturation that may explain the molecular pathogenesis of Rett syndrome (PMID:16682435)
• ID4 gene might be inactivated by DNA hypermethylation, and may function as a tumor suppressir gene in malignant lymphoma (PMID:17510533)
• new subgroup of b-cell precursor acute lymphoblastic leukemia characterized by ID4 over-expression and CDKN2A and PAX5 deletions (PMID:17940204)
• As compared with healthy individuals, Id4 gene in acute leukemia patients was methylated in different degrees. (PMID:18088456)
• id4 gene methylation may be an indicator for multidrug resistance in non-Hodgkins lymphoma patients without bone marrow involvement. (PMID:18426657)
• ID4 is a novel tumour suppressor gene in normal human breast tissue and is epigenetically silenced during cancer development, indicating increased risk for tumour relapse. (PMID:18513385)
• id4 promoter methylation might be a predictor for relapse of AML patients with complete remission. (PMID:18549611)
• Cdc42 was found to be overexpressed with high incidence (60%) in colorectal cancer samples, and this expression was associated with silencing of ID4 with statistical significance (p<0.05). (PMID:18575765)
• ID4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling. (PMID:18676808)
• The aim of this study was to unravel the role of the transcription factor inhibitor of DNA binding 4 (ID4) in human breast carcinogenesis in more detail, especially the impact of ID4 promoter methylation on disease progression. (PMID:18807039)
• Methylation of Id4 promoter could indicate an increased risk of relapse in acute lymphoblastic leukemia. (PMID:18928580)
• Id4 gene was methylated in leukemia and lymphoma cell lines. (PMID:19099656)
• increased frequency of promoter hypermethylation in ID4 gene in acute myeloid leukemia compared to chronic myeloid leukemia. (PMID:19543515)
• Id4 gene methylation is found in myelodysplastic syndrome patients with higher ratio of blast cells. (PMID:19549375)
• analysis of the transcriptional axis mutant p53, E2F1 and ID4 which promotes tumor neo-angiogenesis (PMID:19783986)
• Our results suggest that ID4 may be a therapeutic target in myelodysplastic syndrome (PMID:19853913)
• Study confirms the importance of the silencing of ID4 in murine and human CLL pathogenesis. (PMID:21098398)
• The zo-1 and id4 genes in multiple myeloma cell lines all were methylation positive, and the methylation positive rates were significantly higher than in normal bone marrow. (PMID:21129259)
• The id4 gene promoter in CML patients is unmethylated in chronic phase, but it is methylated in accelerated phase and blast crisis. (PMID:21176338)
• Results reveal a novel regulatory mechanism by which ID4-driven suppression of miR-9* induces SOX2, which imparts stemness potential and chemoresistance to glioma cells and GSCs. (PMID:21531766)
• Hypermethylation of the promoter was associated with loss of inhibitor of differentiation 4 (ID4) messenger RNA and protein expression. (PMID:21663940)
• Compared with ron deficiency anemia patients, ID4 gene methylation changes of different degrees occur in AML patients with different subtypes and stages. (PMID:21729527)
• ID4 downregulation may contribute to prostate cancer pathogenesis and is often accompanied by DNA hypermethylation. (PMID:21882048)
• methyltransferase inhibitor 5-Aza-CdR can re-express the silent ID4 gene in K562 cells (PMID:22169289)
• Id2 and Id4 regulated glioblastoma multiforme neurosphere differentiation through downregulating of another bHLH family member, the oligodendroglial lineage-associated transcription factors (Olig) 1 and 2 (PMID:22380883)
• Results showed that DPP6, SPHKAP and ID4 were down regulated in acute myeloid leukemia (AML) patients. (PMID:22479372)
• Id4 overexpression plays a role in the downregulation of BRCA1 in sporadic TNBCs of patients without BRCA1 germline mutation, and provide new insight into the biology of these tumors. (PMID:22538771)
• These data suggest that methylation of Id4 may be involved in the pathogenesis of GBM and in the resistance of this neoplasm to conventional treatment throughout MGP-mediated neoangiogenesis. (PMID:23132729)
• these results demonstrate loss of Id4 expression in prostate cancer due to promoter hypermethylation. The data strongly support the role of Id4 as a tumor suppressor. (PMID:23342267)
• Because both ID4 alone and a complex of SOX4 and OCT-4 activate SOX2 transcription, it is possible that multiple activation of SOX2 impair the prognosis of glioblastoma patients. (PMID:23613880)
• The methylation positivity rates of the ID4 and ZO-1 genes in the bone marrow and paraffin-embedded lymphoma tissues of non-Hodgkin lymphoma patients were significantly higher compared to the rates in the Hodgkin lymphoma patients. (PMID:23670122)
• Id4 regulates NKX3.1, Sox9 and PTEN. (PMID:23786676)
• Id4 may alter molecular pathways such as those involving E2F1 to promote senescence and increased sensitivity to doxorubicin-induced apoptosis. (PMID:24122992)
• results suggest that Id4 regulates the activity of p53 and promoted the assembly of a macromolecular complex involving CBP/P300 that resulted in acetylation of p53 at K373, a critical post-translational modification required for its biological activity. (PMID:24330748)
• study shows that Id2, Id3 and Id4 are each able to overcome TGF-beta dependence, and establish a role for Ids as key mediators of TGF-beta melanomagenesis (PMID:24343358)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	id4	ENSDARG00000045131
mus_musculus	Id4	ENSMUSG00000021379
rattus_norvegicus	Id4	ENSRNOG00000016099
drosophila_melanogaster	emc	FBGN0000575

Paralogs (3): ID2 (ENSG00000115738), ID3 (ENSG00000117318), ID1 (ENSG00000125968)

Protein

Protein identifiers

DNA-binding protein inhibitor ID-4 — P47928 (reviewed: P47928)

Alternative names: Class B basic helix-loop-helix protein 27, Inhibitor of DNA binding 4, Inhibitor of differentiation 4

All UniProt accessions (1): P47928

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.

Subunit / interactions. Heterodimer with other HLH proteins.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001537* (*=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 (7 total): sequence conflict 3, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47928-F1	68.34	0.31

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9830364	Formation of the nephric duct

MSigDB gene sets: 335 (showing top): GOBP_CIRCADIAN_RHYTHM, AHRARNT_01, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_GLAND_MORPHOGENESIS, CCAWYNNGAAR_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_OLIGODENDROCYTE_DIFFERENTIATION, GOBP_PROSTATE_GLAND_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, PEREZ_TP63_TARGETS

GO Biological Process (29): G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), positive regulation of neuroblast proliferation (GO:0002052), neuroblast proliferation (GO:0007405), circadian rhythm (GO:0007623), intracellular protein localization (GO:0008104), positive regulation of gene expression (GO:0010628), hippocampus development (GO:0021766), cerebral cortex neuron differentiation (GO:0021895), central nervous system myelination (GO:0022010), neuron differentiation (GO:0030182), fat cell differentiation (GO:0045444), negative regulation of fat cell differentiation (GO:0045599), negative regulation of neuron differentiation (GO:0045665), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), astrocyte differentiation (GO:0048708), negative regulation of astrocyte differentiation (GO:0048712), negative regulation of oligodendrocyte differentiation (GO:0048715), prostate gland epithelium morphogenesis (GO:0060740), prostate gland stromal morphogenesis (GO:0060741), seminal vesicle morphogenesis (GO:0061682), brain development (GO:0007420), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), central nervous system neuron differentiation (GO:0021953), oligodendrocyte differentiation (GO:0048709), prostate gland morphogenesis (GO:0060512)

GO Molecular Function (5): transcription corepressor activity (GO:0003714), protein dimerization activity (GO:0046983), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), 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-2 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
generation of neurons	2
regulation of gene expression	2
negative regulation of cell differentiation	2
negative regulation of glial cell differentiation	2
cellular anatomical structure	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
ossification	1
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
neural precursor cell proliferation	1
rhythmic process	1
macromolecule localization	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
pallium development	1
limbic system development	1
anatomical structure development	1
forebrain neuron differentiation	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
myelination	1
fat cell differentiation	1
regulation of fat cell differentiation	1
neuron differentiation	1
regulation of neuron differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
central nervous system development	1
glial cell differentiation	1
astrocyte differentiation	1

Protein interactions and networks

STRING

1580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ID4	OLIG1	Q8TAK6	944
ID4	OLIG2	Q13516	932
ID4	ASCL1	P50553	900
ID4	TCF3	P15883	743
ID4	ID1	P41134	714
ID4	WNT5A	P41221	692
ID4	SRSF1	Q07955	687
ID4	NANOS2	P60321	611
ID4	GFRA1	P56159	610
ID4	HES5	Q5TA89	591
ID4	ZBTB16	Q05516	585
ID4	TCF12	Q99081	580
ID4	MYOD1	P15172	577
ID4	BCL6B	Q8N143	559
ID4	SOX9	P48436	556
ID4	SMAD9	O15198	556

IntAct

32 interactions, top by confidence:

A	B	Type	Score
TAL1	TCF4	psi-mi:“MI:0914”(association)	0.690
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
ID4	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
MYOG	TCF4	psi-mi:“MI:0914”(association)	0.530
TCF4	CBFA2T3	psi-mi:“MI:0914”(association)	0.530
ID4	CRK	psi-mi:“MI:0915”(physical association)	0.400
ID4	SRC	psi-mi:“MI:0915”(physical association)	0.400
GRB2	ID4	psi-mi:“MI:0915”(physical association)	0.400
ID4	NCK1	psi-mi:“MI:0915”(physical association)	0.400
PIK3R1	ID4	psi-mi:“MI:0915”(physical association)	0.400
ID4	PLCG1	psi-mi:“MI:0915”(physical association)	0.400
TCF4	TRIM24	psi-mi:“MI:0914”(association)	0.350
TCF4	OGT	psi-mi:“MI:0914”(association)	0.350
ID2	CLASP2	psi-mi:“MI:0914”(association)	0.350
MYF6	TBC1D4	psi-mi:“MI:0914”(association)	0.350
TCF4	CBFA2T3	psi-mi:“MI:0914”(association)	0.350
METTL2A	NDUFS6	psi-mi:“MI:0914”(association)	0.350
TAL1	PRPF40A	psi-mi:“MI:0914”(association)	0.350
TCF4	HMGB1	psi-mi:“MI:0914”(association)	0.350
FIGLA	TCF4	psi-mi:“MI:0914”(association)	0.350
ASCL3	TCF4	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): ID4 (Affinity Capture-MS), ID4 (Affinity Capture-MS), ID4 (Affinity Capture-MS), ID4 (Affinity Capture-MS), ID4 (Affinity Capture-MS), ID4 (Affinity Capture-MS), ID4 (Affinity Capture-MS), OLIG1 (Affinity Capture-Western), ID4 (Affinity Capture-Western), OLIG2 (Affinity Capture-Western), ID4 (Affinity Capture-Western), ID4 (Affinity Capture-MS), ID4 (Affinity Capture-RNA), ID4 (Affinity Capture-MS), ID4 (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

1 interactions.

A	Effect	B	Mechanism
ID4	“up-regulates quantity by expression”	SOX2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
Downstream signal transduction	6	103.8×	5e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

229 predictions. Top by Δscore:

Variant	Effect	Δscore
6:19838640:CAGGT:C	donor_loss	1.0000
6:19838641:AGGT:A	donor_loss	1.0000
6:19838642:GGTG:G	donor_loss	1.0000
6:19838643:G:GA	donor_loss	1.0000
6:19838644:T:A	donor_loss	1.0000
6:19838195:GGTG:G	donor_loss	0.9900
6:19838196:G:GG	donor_gain	0.9900
6:19838197:T:A	donor_loss	0.9900
6:19838569:C:CA	acceptor_gain	0.9900
6:19838570:G:A	acceptor_gain	0.9900
6:19838576:T:TA	acceptor_gain	0.9900
6:19838582:A:AG	acceptor_gain	0.9900
6:19838583:G:GG	acceptor_gain	0.9900
6:19839205:CACAG:C	acceptor_loss	0.9900
6:19839207:CAGGT:C	acceptor_loss	0.9900
6:19839208:AGGTG:A	acceptor_loss	0.9900
6:19839209:GGT:G	acceptor_gain	0.9900
6:19838198:GAGAG:G	donor_loss	0.9800
6:19838580:CCAGG:C	acceptor_loss	0.9800
6:19838581:CAGGC:C	acceptor_loss	0.9800
6:19838582:AGGCC:A	acceptor_gain	0.9800
6:19838583:G:A	acceptor_loss	0.9800
6:19838583:GGCC:G	acceptor_gain	0.9800
6:19838583:GGCCG:G	acceptor_gain	0.9800
6:19838643:G:GG	donor_gain	0.9800
6:19839206:A:AG	acceptor_gain	0.9800
6:19839207:C:G	acceptor_gain	0.9800
6:19839208:A:AG	acceptor_gain	0.9800
6:19839209:G:GA	acceptor_gain	0.9800
6:19839209:GGTGT:G	acceptor_gain	0.9800

AlphaMissense

1020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:19837968:T:C	Y72H	1.000
6:19837978:T:A	L75Q	1.000
6:19837978:T:C	L75P	1.000
6:19837987:T:C	L78P	1.000
6:19837989:G:A	V79M	1.000
6:19837992:C:T	P80S	1.000
6:19837999:T:A	I82N	1.000
6:19837999:T:C	I82T	1.000
6:19838020:G:T	S89I	1.000
6:19838035:T:A	L94Q	1.000
6:19838035:T:C	L94P	1.000
6:19838038:A:C	Q95P	1.000
6:19838039:G:C	Q95H	1.000
6:19838039:G:T	Q95H	1.000
6:19838043:G:C	V97L	1.000
6:19838044:T:A	V97D	1.000
6:19838047:T:A	I98N	1.000
6:19838047:T:G	I98S	1.000
6:19838050:A:C	D99A	1.000
6:19838050:A:G	D99G	1.000
6:19838050:A:T	D99V	1.000
6:19838052:T:C	Y100H	1.000
6:19838056:T:A	I101N	1.000
6:19838056:T:C	I101T	1.000
6:19838056:T:G	I101S	1.000
6:19838059:T:C	L102P	1.000
6:19838065:T:A	L104Q	1.000
6:19838065:T:C	L104P	1.000
6:19837965:T:C	C71R	0.999
6:19837966:G:A	C71Y	0.999

dbSNP variants (sampled 300 via entrez): RS1001068749 (6:19838758 C>T), RS1001213342 (6:19839827 T>C), RS1001762212 (6:19835500 C>T), RS1002166679 (6:19839947 CTT>C), RS1002616573 (6:19839228 C>G), RS1002655367 (6:19836480 G>A,T), RS1002761479 (6:19839315 CTAGA>C), RS1003387888 (6:19842155 G>T), RS1004071804 (6:19839392 C>G), RS1004174691 (6:19838748 G>A), RS1004190067 (6:19839629 A>G), RS1004327334 (6:19839748 C>A), RS1005157816 (6:19836001 C>G,T), RS1005218483 (6:19838846 A>G), RS1005334557 (6:19838771 TCC>T,TC)

Disease associations

OMIM: gene MIM:600581 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000635_19	Response to statin therapy	7.000000e-07
GCST000817_83	Height	2.000000e-13
GCST001894_9	Endometriosis	2.000000e-07
GCST003773_6	Loneliness (multivariate analysis)	2.000000e-06
GCST003994_4	Age at voice drop	1.000000e-07
GCST004368_1	Endometriosis	5.000000e-07
GCST004370_8	Deep ovarian and/or rectovaginal disease with dense adhesions	7.000000e-07
GCST004549_1	Endometriosis	7.000000e-08
GCST004549_16	Endometriosis	2.000000e-10
GCST006896_16	Free thyroxine concentration	6.000000e-12
GCST007293_56	Body fat distribution (arm fat ratio)	6.000000e-08
GCST007294_145	Body fat distribution (trunk fat ratio)	4.000000e-20
GCST007294_84	Body fat distribution (trunk fat ratio)	1.000000e-38
GCST007295_103	Body fat distribution (leg fat ratio)	2.000000e-15
GCST007295_108	Body fat distribution (leg fat ratio)	7.000000e-29
GCST007329_41	Automobile speeding propensity	3.000000e-12
GCST007485_5	Anthropometric traits	1.000000e-129
GCST007490_12	Anthropometric traits (multi-trait analysis)	4.000000e-78
GCST007576_210	Chronotype	3.000000e-09
GCST007576_421	Chronotype	3.000000e-09
GCST007692_119	Chronic obstructive pulmonary disease	5.000000e-14
GCST008163_310	Height	6.000000e-12
GCST008163_504	Height	4.000000e-17
GCST009440_5	Age-related cognitive decline (attention/processing speed) (slope of z-scores)	9.000000e-06
GCST012226_31	Waist circumference adjusted for body mass index	4.000000e-17
GCST012227_880	Hip circumference adjusted for BMI	1.000000e-21
GCST90000025_521	Appendicular lean mass	3.000000e-47
GCST90000050_39	Age at first birth	2.000000e-08
GCST90020028_917	Hip circumference adjusted for BMI	4.000000e-12
GCST90020028_919	Hip circumference adjusted for BMI	2.000000e-39

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0007888	age at voice drop
EFO:0004341	body fat distribution
EFO:0008579	risk-taking behaviour
EFO:0004324	body weights and measures
EFO:0008328	chronotype measurement
EFO:0007710	cognitive decline measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0009101	age at first birth measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	9
sodium arsenite	decreases expression, increases expression	3
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases methylation, decreases expression, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
nickel sulfate	increases expression	1
hydroquinone	increases expression	1
avobenzone	decreases expression	1
polyhexamethyleneguanidine	increases expression	1
harringtonin	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases methylation, increases expression	1
Homoharringtonine	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amphotericin B	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7UL	e-hUVEC-4	Transformed cell line

Clinical trials (associated diseases)

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