FOXQ1

Summary

FOXQ1 (forkhead box Q1, HGNC:20951) is a protein-coding gene on chromosome 6p25.3, encoding Forkhead box protein Q1 (Q9C009). Plays a role in hair follicle differentiation.

FOXQ1 is a member of the FOX gene family, which is characterized by a conserved 110-amino acid DNA-binding motif called the forkhead or winged helix domain. FOX genes are involved in embryonic development, cell cycle regulation, tissue-specific gene expression, cell signaling, and tumorigenesis (Bieller et al., 2001 [PubMed 11747606]).

Source: NCBI Gene 94234 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 122 total — 1 pathogenic
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_033260

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20951
Approved symbol	FOXQ1
Name	forkhead box Q1
Location	6p25.3
Locus type	gene with protein product
Status	Approved
Aliases	HFH1
Ensembl gene	ENSG00000164379
Ensembl biotype	protein_coding
OMIM	612788
Entrez	94234

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000296839

RefSeq mRNA: 1 — MANE Select: NM_033260 NM_033260

CCDS: CCDS4471

Canonical transcript exons

ENST00000296839 — 1 exons

Exon	Start	End
ENSE00001083937	1312098	1314758

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 99.04.

FANTOM5 (CAGE): breadth broad, TPM avg 14.1108 / max 1591.2897, expressed in 900 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65419	13.5016	876
65418	0.4739	258
65420	0.0747	29
65421	0.0606	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.04	gold quality
pylorus	UBERON:0001166	98.94	gold quality
epithelial cell of pancreas	CL:0000083	98.55	gold quality
pancreatic ductal cell	CL:0002079	98.53	gold quality
endothelial cell	CL:0000115	98.06	gold quality
upper arm skin	UBERON:0004263	96.89	gold quality
palpebral conjunctiva	UBERON:0001812	96.25	gold quality
skin of hip	UBERON:0001554	96.20	gold quality
secondary oocyte	CL:0000655	95.40	gold quality
upper leg skin	UBERON:0004262	95.40	gold quality
gingival epithelium	UBERON:0001949	95.10	gold quality
gingiva	UBERON:0001828	94.82	gold quality
esophagus squamous epithelium	UBERON:0006920	94.59	gold quality
trachea	UBERON:0003126	94.25	gold quality
urethra	UBERON:0000057	93.86	gold quality
kidney epithelium	UBERON:0004819	93.67	gold quality
nasal cavity epithelium	UBERON:0005384	93.54	gold quality
cardia of stomach	UBERON:0001162	93.52	gold quality
nipple	UBERON:0002030	93.00	gold quality
amniotic fluid	UBERON:0000173	92.76	gold quality
pharyngeal mucosa	UBERON:0000355	92.22	gold quality
epithelium of nasopharynx	UBERON:0001951	91.83	gold quality
mammalian vulva	UBERON:0000997	91.64	gold quality
superior surface of tongue	UBERON:0007371	91.27	gold quality
tongue	UBERON:0001723	89.00	gold quality
renal medulla	UBERON:0000362	88.93	gold quality
lower lobe of lung	UBERON:0008949	88.55	gold quality
eye	UBERON:0000970	87.15	gold quality
body of tongue	UBERON:0011876	86.83	gold quality
penis	UBERON:0000989	86.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	63.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
BCL11A	Activation
BGLAP
BMP4
CDH1	Unknown
CDH17
CDKN1A	Activation
EIF3K
FOXQ1
IBSP
IGFBP6
ITK
MYLK	Repression
NRXN3
RSPO2	Activation
TAGLN	Repression
TWIST1	Activation
VCAN	Activation
VEGFA	Activation
WNT3A	Activation
ZEB2	Unknown

Upstream regulators (CollecTRI, top): FOXQ1, NACC1

miRNA regulators (miRDB)

78 targeting FOXQ1, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 40)

• Transforming growth factor-beta 2 is a transcriptional target for Akt/protein kinase B via this protein (PMID:12011061)
• This study demenostrated that the forkhead transcription factor is reduced in skeletal muscle of chronic spinal cord-injured patients. (PMID:19533653)
• FOXQ1 overexpression upregulated several genes that have positive roles for tumor growth of colorectal cancer. (PMID:20145154)
• Foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis. (PMID:21285253)
• Mechanistic investigations revealed that FOXQ1-induced EMT was associated with transcriptional inactivation of the epithelial regulator E-cadherin. Findings define a key role for FOXQ1 in regulating EMT and aggressiveness in human cancer. (PMID:21346143)
• this study showed that an interaction between FOXQ1 and SUMO1P1 for psychomotor speed. (PMID:22126837)
• Increased levels of this transcription factor suggest a potential link with cell dysfunction induced by altered prelamin A metabolism. (PMID:22948034)
• FOXQ1 expression is essential to maintain cell proliferation, motility/invasion, and epithelial-mesenchymal transition phenotypes in ovarian cancer cells. (PMID:23203039)
• FoxQ1 promotes glioma cell proliferation and migration by down-regulation of NRXN3 expression. (PMID:23383267)
• FOXQ1 may be a novel epithelial-mesenchymal transition-inducing transcription factor through controlling the expression of E-cadherin. (PMID:23403865)
• Data show that FOXQ1 is one of the most over-expressed genes in CRC and a direct target of the canonical Wnt pathway. (PMID:23555880)
• FOXQ1 expression level is an independent prognostic factor for the overall survival rate of gastric cancer patients. (PMID:23609035)
• Study demonstrates that an aggressive malignant phenotype of hepatocellular carcinoma is strongly linked to high FOXQ1 expression. (PMID:23623360)
• results show that FOXQ1 is a novel modulator of Twist1 expression and a regulator of colorectal cancer invasion and metastasis (PMID:23723077)
• FoxQ1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression. (PMID:24005989)
• NAC1 is essential and sufficient for activation of FOXQ1 (PMID:24200849)
• High FoxQ1 expression is associated with hepatocarcinoma. (PMID:24211718)
• Data indicate that knockdown of forkhead box Q1 protein FoxQ1 by its siRNA in cancer stem-like cells (CSLCs) resulted in the inhibition of aggressive behavior. (PMID:24719318)
• Results demonstrate that miR-124 functions as a tumor-suppressive microRNA in nasopharyngeal carcinoma by repressing Foxq1 expression. (PMID:25098939)
• critical role in the regulation of hepatocellular carcinoma development (PMID:25251503)
• NSCLC cells with silenced FoxQ1 had decreased cell proliferation, migration and invasion in cell culture and delayed growth of xenograft tumors in mice compared with corresponding control cells. (PMID:25356753)
• PDGFRalpha and beta can be directly regulated by Foxq1 or indirectly regulated through the Foxq1/Twist1 axis (PMID:25502837)
• Data suggest that forkhead box Q1 (FOXQ1) is a potential therapeutic target for the development of therapies for colorectal cancer. (PMID:25955104)
• FoxQ1 expression is negatively associated with the overall survival of PC patients, and that this protein may therefore represent a novel molecular target and new prognostic biomarker for PC. (PMID:26122655)
• MiR-1271 inhibits cell proliferation, invasion, and epithelial-mesenchymal transition in gastric cancer by directly suppressing FOXQ1 expression. (PMID:26159618)
• we identified FOXQ1 as an oncogene to promote ESCC tumor cell proliferation and metastasis by negatively regulating CDH1 in esophageal squamous cell carcinoma cells (PMID:26349968)
• MiR-133 directly targeted and down-regulated FOXQ1 expression, which in turn reduced TGF-beta level. (PMID:26858166)
• The miR-506/FOXQ1 axis plays an important role in the pathogenesis of cervical cancer. (PMID:26935526)
• FOXQ1 is a prognostic marker for patients with Gastric cancer, FOXQ1 over-expression is involved in acquisition of the mesenchymal phenotype of gastric cancer cells, and subsequent Snail expression is essential for induction of Epithelial-Mesenchymal Transition. (PMID:27109028)
• Data indicate a role for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting colorectal cancer (CRC) development and suggest targeting those networks as potential therapeutic strategy for CRC. (PMID:27119506)
• DATS administration inhibited ALDH1 activity in vivo in SUM159 xenografts. These results indicate that FoxQ1 is a novel target of bCSC inhibition by DATS. (PMID:27129776)
• We identified FOXM1 and FOXQ1 as novel prognostic biomarkers in colorectal cancer and miR-342 as a novel regulator of both FOXM1 and FOXQ1 (PMID:27162244)
• There are several modes of regulation of FOXQ1 expression that have been demonstrated in normal and tumor cells, such as microRNA and the Wnt signaling pathway. The activation of FOXQ1 affects downstream genes promoting the initiation, proliferation and invasion, in addition to the metastasis of tumor cells (PMID:27176124)
• our study suggests that FOXQ1 regulates prostate cancer cell proliferation and apoptosis by regulating BCL11A/MDM2 expression and indicates that FOXQ1 may serve as a potential therapeutic target for prostate cancer. (PMID:27573292)
• FOXQ1 remarkably inhibited the replicative senescence through depressing the expression of the inflammatory cytokines interleukin-6 (IL-6) and IL-8 via modulation of SIRT1-NF-kappaB pathway. (PMID:28726780)
• Results revealed that, co-culture with TAMs promoted the invasion and migration of GC cells. Co-culture with TAMs induced EMT in GC cells. FOXQ1 is essential for TAM-induced EMT and metastasis in GC cells. (PMID:28791370)
• These data identify FOXQ1 as a melanoma suppressor. (PMID:28930679)
• Results show that FOXQ1, a well-known oncogenic protein and promoter of gastric cancer (GC) metastasis, to be the direct downstream target of miR-345 in GC. Its mRNA and protein levels are up-regulated in GC tumors. (PMID:29048674)
• inhibition of FOXQ1 restricted natural killer/T-cell lymphoma cell proliferation and growth but induced apoptosis (PMID:29132010)
• Findings indicate a positive feedback loop between cancer associated fibroblast (CAFs) and box Q1 (FOXQ1)/N-myc downstream-regulated gene 1 (NDRG1) axis in neoplastic cells to drive hepatocellular carcinoma (HCC) initiation, suggesting new potential therapeutic targets for HCC. (PMID:29248714)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxq1a	ENSDARG00000030896
danio_rerio	foxq1b	ENSDARG00000055395
mus_musculus	Foxq1	ENSMUSG00000038415
rattus_norvegicus	Foxq1	ENSRNOG00000062314

Paralogs (41): FOXP3 (ENSG00000049768), FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXM1 (ENSG00000111206), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), FOXJ1 (ENSG00000129654), FOXK2 (ENSG00000141568), FOXO1 (ENSG00000150907), FOXH1 (ENSG00000160973), FOXK1 (ENSG00000164916), FOXD4 (ENSG00000170122), FOXA3 (ENSG00000170608), FOXB1 (ENSG00000171956), FOXR1 (ENSG00000176302), FOXL1 (ENSG00000176678), FOXC2 (ENSG00000176692), FOXE1 (ENSG00000178919), FOXS1 (ENSG00000179772), FOXL2 (ENSG00000183770), FOXO4 (ENSG00000184481), FOXD4L1 (ENSG00000184492), FOXD4L4 (ENSG00000184659), FOXD2 (ENSG00000186564), FOXI2 (ENSG00000186766), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein Q1 — Q9C009 (reviewed: Q9C009)

Alternative names: HNF-3/forkhead-like protein 1, Hepatocyte nuclear factor 3 forkhead homolog 1

All UniProt accessions (1): Q9C009

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in hair follicle differentiation.

Subcellular location. Nucleus.

Tissue specificity. Expressed predominantly in the stomach, trachea, bladder and salivary gland.

RefSeq proteins (1): NP_150285* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR018122	TF_fork_head_CS_1	Conserved_site
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR047518	FH_FOXQ1	Domain
IPR050211	FOX_domain-containing	Family

Pfam: PF00250

UniProt features (13 total): sequence conflict 3, region of interest 3, compositionally biased region 3, sequence variant 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C009-F1	61.92	0.19

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription

MSigDB gene sets: 140 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_EPIDERMIS_MORPHOGENESIS, WWTAAGGC_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, BILD_HRAS_ONCOGENIC_SIGNATURE, GTGCCTT_MIR506, chr6p25, BILD_E2F3_ONCOGENIC_SIGNATURE, LIAO_METASTASIS, GOBP_MOLTING_CYCLE, GOBP_EPIDERMIS_DEVELOPMENT, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), anatomical structure morphogenesis (GO:0009653), cell differentiation (GO:0030154), hair follicle morphogenesis (GO:0031069), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): 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, RNA polymerase II-specific (GO:0001227), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
developmental process	1
anatomical structure development	1
cellular developmental process	1
hair follicle development	1
anatomical structure morphogenesis	1
hair cycle process	1
epidermis morphogenesis	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
chromosome	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXQ1	GMDS	O60547	770
FOXQ1	CYP1B1	Q16678	713
FOXQ1	HOXC13	P31276	677
FOXQ1	TPPP	O94811	649
FOXQ1	FOXF2	Q12947	563
FOXQ1	MESP1	Q9BRJ9	560
FOXQ1	TCF15	Q12870	559
FOXQ1	CTNNB1	P35222	552
FOXQ1	GATA6	P78327	503
FOXQ1	ATOH1	Q92858	498
FOXQ1	PITX2	Q99697	474
FOXQ1	NQO1	P15559	450
FOXQ1	CRIM1	Q9NZV1	444
FOXQ1	MESP2	Q0VG99	438
FOXQ1	FEN1	P39748	429
FOXQ1	EFNB2	P52799	429

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FOXQ1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
FOXQ1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXQ1	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
FOXQ1	TIMM8A	psi-mi:“MI:0914”(association)	0.350
FOXQ1	ZNF609	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (140): NUP205 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), SMARCA5 (Affinity Capture-MS), ASH2L (Affinity Capture-MS), CHD4 (Affinity Capture-MS), NUP160 (Affinity Capture-MS), ADNP (Affinity Capture-MS), GTF3C5 (Affinity Capture-MS), NUP133 (Affinity Capture-MS), RBBP5 (Affinity Capture-MS), VARS (Affinity Capture-MS), GTF3C4 (Affinity Capture-MS), PDS5A (Affinity Capture-MS), POLE (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA5, A0A286YF58, A0A494C0N9, A0A494C0Y3, A0A7I2V3R4, A0JNN8, A2ARS0, A2VDX9, A5PJP1, A6NGB7, A8MVW0, C9JTQ0, O14511, O14559, O35392, O35569, O43541, O60548, O70220, P0DPE3, Q08102, Q14V87, Q19A40, Q29RK8, Q2HJ59, Q3TYP4, Q5BLP8, Q5T442, Q63244, Q6F5E0, Q6QNY0, Q6VUP9, Q80WY3, Q80XF7, Q8BQU6, Q8K025, Q8K071, Q8TD94, Q8WY41, Q8WZ71

Diamond homologs: A0A8V0YY16, A1L1S5, A8MTJ6, B5RHS5, D3Z120, O00358, O35392, O42097, O43638, O54743, O60548, O70220, O88470, P14734, P32027, P32030, P35583, P58012, P79772, P84961, P91278, Q02360, Q02361, Q07342, Q12946, Q12947, Q12948, Q12950, Q12951, Q12952, Q13461, Q16676, Q17241, Q18694, Q28BS5, Q28D67, Q32NP8, Q3I5G5, Q3SYB3, Q4VUF1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXQ1	“down-regulates quantity by repression”	MYLK	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	112
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
973776	GRCh37/hg19 6p25.3(chr6:1318643-1837594)x3	Pathogenic

SpliceAI

146 predictions. Top by Δscore:

Variant	Effect	Δscore
6:1312665:G:GT	donor_gain	0.9000
6:1313175:C:CA	acceptor_gain	0.8000
6:1312670:GG:G	donor_gain	0.7900
6:1312671:GG:G	donor_gain	0.7900
6:1312668:GAGG:G	donor_gain	0.7700
6:1312579:AG:A	donor_gain	0.6400
6:1312567:G:GT	donor_gain	0.6100
6:1312669:AGG:A	donor_loss	0.6000
6:1312670:GGGTA:G	donor_loss	0.6000
6:1312671:GGTAC:G	donor_loss	0.6000
6:1312673:T:TC	donor_loss	0.6000
6:1313239:A:AC	acceptor_gain	0.6000
6:1312674:A:C	donor_loss	0.5800
6:1313152:ATGGG:A	acceptor_gain	0.5600
6:1313155:GGCAA:G	acceptor_gain	0.5600
6:1313156:GCAAG:G	acceptor_gain	0.5600
6:1313159:A:AT	acceptor_gain	0.5500
6:1312675:CGACG:C	donor_loss	0.5400
6:1312559:C:G	donor_gain	0.5300
6:1313153:TGGGC:T	acceptor_gain	0.5200
6:1313154:GGG:G	acceptor_gain	0.5200
6:1313181:C:G	acceptor_gain	0.5200
6:1313179:A:AG	acceptor_gain	0.5100
6:1313180:G:GG	acceptor_gain	0.5100
6:1312672:G:GG	donor_gain	0.5000
6:1313157:CAAGT:C	acceptor_gain	0.5000
6:1312578:T:TA	donor_gain	0.4900
6:1313158:AAG:A	acceptor_gain	0.4700
6:1313395:G:GT	donor_gain	0.4700
6:1312962:G:GA	donor_gain	0.4600

AlphaMissense

2546 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:1313074:T:C	Y124H	1.000
6:1313084:T:A	L127H	1.000
6:1313084:T:C	L127P	1.000
6:1313087:T:A	I128N	1.000
6:1313099:T:A	I132N	1.000
6:1313161:T:C	F153L	1.000
6:1313163:C:A	F153L	1.000
6:1313163:C:G	F153L	1.000
6:1313167:T:C	F155L	1.000
6:1313169:T:A	F155L	1.000
6:1313169:T:G	F155L	1.000
6:1313170:T:C	F156L	1.000
6:1313171:T:C	F156S	1.000
6:1313171:T:G	F156C	1.000
6:1313172:C:A	F156L	1.000
6:1313172:C:G	F156L	1.000
6:1313191:T:A	W163R	1.000
6:1313191:T:C	W163R	1.000
6:1313193:G:C	W163C	1.000
6:1313193:G:T	W163C	1.000
6:1313198:A:T	N165I	1.000
6:1313199:C:A	N165K	1.000
6:1313199:C:G	N165K	1.000
6:1313209:C:A	H169N	1.000
6:1313209:C:G	H169D	1.000
6:1313211:C:A	H169Q	1.000
6:1313211:C:G	H169Q	1.000
6:1313212:A:G	N170D	1.000
6:1313213:A:T	N170I	1.000
6:1313214:C:A	N170K	1.000

dbSNP variants (sampled 300 via entrez): RS1000204717 (6:1310132 T>C), RS1000469060 (6:1312599 G>A), RS1001130890 (6:1314674 C>A,G), RS1001449230 (6:1311001 C>T), RS1002143293 (6:1313578 G>A,C,T), RS1002195569 (6:1313450 C>G,T), RS1002214547 (6:1312160 G>T), RS1002456703 (6:1312077 G>C), RS1005095667 (6:1312185 C>T), RS1005467716 (6:1310983 G>A,C), RS1006259788 (6:1311863 T>C,G), RS1007272653 (6:1310793 A>C), RS1007293542 (6:1312481 T>A,G), RS1007489280 (6:1315005 A>T), RS1007934300 (6:1312927 G>A)

Disease associations

OMIM: gene MIM:612788 | disease phenotypes: MIM:601631

GenCC curated gene-disease

Mondo (1): anterior segment dysgenesis 3 (MONDO:0024456)

Orphanet (1): Rieger anomaly (Orphanet:91483)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000745_3	Pancreatic cancer	3.000000e-07
GCST001599_2	Aging	9.000000e-06
GCST001937_57	Breast cancer	7.000000e-09
GCST002380_3	Erythema nodosum in inflammatory bowel disease	8.000000e-06
GCST003491_1	Stroke	1.000000e-08
GCST003518_8	Daytime sleep phenotypes	1.000000e-06
GCST006979_484	Heel bone mineral density	6.000000e-09
GCST007102_13	Seasonality and depression	1.000000e-06
GCST008830_18	Neurofibrillary tangles	1.000000e-07
GCST010727_16	Deep white matter hyperintensities	1.000000e-07

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0007828	daytime rest measurement
EFO:0009270	heel bone mineral density
EFO:0006876	seasonality measurement
EFO:0006797	neurofibrillary tangles measurement
EFO:0005665	white matter hyperintensity measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535535	Iridogoniodysgenesis type1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Cyclosporine	increases expression	3
Aflatoxin B1	affects expression, increases expression	3
bisphenol A	affects expression, increases expression	2
sodium arsenite	decreases expression, increases abundance	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	increases expression	2
Tobacco Smoke Pollution	increases expression	2
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
arsenite	decreases expression, increases abundance	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tobacco tar	decreases expression	1
diallyl trisulfide	affects localization, decreases expression, decreases reaction, increases expression	1
pentanal	increases expression	1
antimonite	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
quinocetone	decreases expression	1
ormosil	affects binding, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	increases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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