DACH1

Summary

DACH1 (dachshund family transcription factor 1, HGNC:2663) is a protein-coding gene on chromosome 13q21.33, encoding Dachshund homolog 1 (Q9UI36). Transcription factor that is involved in regulation of organogenesis.

This gene encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression and cell fate determination during development. The protein contains a Ski domain that is highly conserved from Drosophila to human. Expression of this gene is lost in some forms of metastatic cancer, and is correlated with poor prognosis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1602 — RefSeq curated summary.

At a glance

• GWAS associations: 40
• Clinical variants (ClinVar): 88 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_080759

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2663
Approved symbol	DACH1
Name	dachshund family transcription factor 1
Location	13q21.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000276644
Ensembl biotype	protein_coding
OMIM	603803
Entrez	1602

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000613252, ENST00000619232, ENST00000706274, ENST00000706275

RefSeq mRNA: 4 — MANE Select: NM_080759 NM_001366712, NM_004392, NM_080759, NM_080760

CCDS: CCDS41899, CCDS91814

Canonical transcript exons

ENST00000613252 — 11 exons

Exon	Start	End
ENSE00003714581	71559820	71559955
ENSE00003721985	71630556	71630717
ENSE00003722940	71557024	71557158
ENSE00003722966	71681795	71681910
ENSE00003725589	71488997	71489148
ENSE00003730456	71572840	71573012
ENSE00003733831	71475141	71475209
ENSE00003743539	71475706	71475849
ENSE00003749106	71479169	71479316
ENSE00003750034	71437966	71440692
ENSE00003847252	71865922	71867204

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 96.60.

FANTOM5 (CAGE): breadth broad, TPM avg 23.7040 / max 1519.1146, expressed in 887 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137567	15.7294	788
137564	4.3316	511
137569	0.8455	274
137561	0.6815	256
137559	0.5699	167
137551	0.4041	174
137563	0.1920	78
137560	0.1521	54
137565	0.1372	67
137552	0.1236	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.60	gold quality
endothelial cell	CL:0000115	92.53	gold quality
ganglionic eminence	UBERON:0004023	89.06	gold quality
buccal mucosa cell	CL:0002336	87.30	gold quality
embryo	UBERON:0000922	86.48	gold quality
renal glomerulus	UBERON:0000074	84.39	gold quality
hair follicle	UBERON:0002073	83.87	gold quality
metanephros	UBERON:0000081	83.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.40	gold quality
visceral pleura	UBERON:0002401	82.86	gold quality
metanephric glomerulus	UBERON:0004736	82.69	gold quality
caudate nucleus	UBERON:0001873	80.84	gold quality
jejunal mucosa	UBERON:0000399	80.78	gold quality
lower lobe of lung	UBERON:0008949	80.20	gold quality
putamen	UBERON:0001874	80.05	gold quality
kidney epithelium	UBERON:0004819	79.56	gold quality
trabecular bone tissue	UBERON:0002483	79.46	gold quality
islet of Langerhans	UBERON:0000006	79.04	gold quality
mammalian vulva	UBERON:0000997	78.31	gold quality
kidney	UBERON:0002113	77.98	gold quality
adrenal tissue	UBERON:0018303	77.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.95	gold quality
gall bladder	UBERON:0002110	77.76	gold quality
ileal mucosa	UBERON:0000331	77.37	gold quality
bone marrow	UBERON:0002371	77.37	gold quality
cortex of kidney	UBERON:0001225	77.31	gold quality
right lung	UBERON:0002167	76.77	gold quality
pleura	UBERON:0000977	76.19	gold quality
caput epididymis	UBERON:0004358	75.52	gold quality
duodenum	UBERON:0002114	75.38	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	46.60
E-HCAD-10	yes	18.87
E-ANND-3	yes	6.54

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
FOS	Repression
KLF4	Repression
LIN28A
LIN28B
NANOG	Repression
PELP1	Unknown
SOX2
TNFSF11	Repression

Upstream regulators (CollecTRI, top): AP1, AR, CEBPA, ESR1, GATA1, HOXA9, HOXD13, HSF2, KMT2A, NCOR1, NFKB, SKIL, SMAD4

miRNA regulators (miRDB)

257 targeting DACH1, 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-1277-5P	100.00	73.95	5056
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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 40)

• forms an alpha/beta structure containing a DNA binding motif similar (PMID:12057194)
• DACH1 bound to endogenous NCoR and Smad4 in cultured cells; Smad4 was required for DACH1 repression of TGF-beta induction of Smad signaling (PMID:14525983)
• identifed DACH enhancers in gene deserts (PMID:14563999)
• The dachshund is required in mushroom body neurons for proper axon guidance and branching in Drosophila melanogaster. (PMID:15818552)
• DACH1 repressed cyclin D1 through a novel mechanism via a c-Jun DNA-binding partner, requiring the DACH1 alpha-helical DS domain which recruits corepressors to the local chromatin. (PMID:16980615)
• DACH1 plays an important role in negative regulation of RANKL gene expression in marrow stromal/preosteoblast cells in the bone microenvironment. (PMID:17891780)
• These data identify a pathway by which an endogenous cell-fate determination factor blocks oncogene-dependent tumor metastasis via a key heterotypic mediator. (PMID:18467491)
• DACH1 is hypermethylated in renal cell carcinoma. (PMID:18639284)
• a statistical significance level for DACH1 in gastric cancer (PMID:18957060)
• DACH1 inhibited ligand-dependent activity of AR mutations identified in patients with androgen-insensitive prostate cancer. The DS domain was sufficient for repression of the AR wild-type but failed to repress an AR acetylation site point mutant. (PMID:19351840)
• The altered expression of human DACH1 has been associated with tumor progression and metastasis. DACH1 inhibits breast cancer cellular proliferation via cyclin D1. (PMID:19502783)
• Data show that DACH1 expression, which is lost in poor prognosis human breast cancer, functions as an endogenous inhibitor of ERalpha function. (PMID:19605405)
• Findings identify a role of EYA4 and possibly interacting SIX and DACH proteins in MPNSTs and suggest the EYA4 pathway as a rational therapeutic target. (PMID:19901965)
• Forkhead signaling is attenuated by the retinal determination factor DACH1 (PMID:20351289)
• DACH1 represses gene transcription through direct DNA binding to the promoter region of target genes by recruiting the transcriptional co-regulator, TCERG1. (PMID:20956529)
• in cells growing in IGF-1 (and unresponsive to EGF), DACH1 is devoid of tumor suppressor activity. (PMID:21558809)
• DACH1 is a distinctive tumor suppressor, which not only suppresses growth of tumor cells but also regulates bFGF-mediated tumor-initiating activity of glioma cells (PMID:21750150)
• DACH1 is highly expressed in metastatic ovarian cancer compared with that of normal, benign, and borderline ovarian tissues and could play an important role in cancer growth. (PMID:22367319)
• The knockdown of DACH1 blocked the cell cycle progression of HL-60 promyeloblastic cells through the decrease of cyclin D1, D3, F, and Cdk 1, 4, and 6 and increase in p21(Cip1), which in turn decreased the phosphorylation of the Rb protein. (PMID:22405764)
• DACH1 gene promoter methylation could lead to a decrease or absence of DACH1 expression in endometrial carcinoma. (PMID:22781112)
• the inability of C/EBPalpha and GATA-1 to down-regulate DACH1 expression induced by MLL-AF9 during myeloid differentiation may contribute to t(9;11) leukemogenesis. (PMID:22902925)
• DACH1 binds p53 to inhibit NSCLC cellular growth. (PMID:23492369)
• DACH1 is frequently methylated in human colorectal cancers (CRC) and methylation of DACH1 may serve as detective and prognostic marker in CRC. (PMID:24149323)
• Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. (PMID:24335958)
• Nuclear DACH1 expression appears to be a Luminal A biomarker predictive of good prognosis, but is not independent of clinical stage, tumour size, NPI status or systemic therapy. (PMID:24392136)
• Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese (PMID:24465431)
• Data indicate that dachshund family transcription factor 1 (DACH1) suppresses gastric cancer cell proliferation, invasion and metastasis by inhibiting transforming growth factor beta (TGF-beta) signalling pathways both in vitro and in vivo. (PMID:24912879)
• Results indicated that DACH1 was a novel molecular marker of RCC and it attributed to the malignant behavior of renal cancer cells. (PMID:25322986)
• In breast cancer, some GATA3 effects shift from tumor suppressing to tumor promoting during tumorigenesis, with deregulation of three genes, BCL2, DACH1, THSD4, representing major GATA3-controlled processes in cancer progression. (PMID:25410484)
• Further evaluation of the methylation of DACH1, DKK1, and WIF1 in a clinical patient group confirmed the frequent methylation of WIF1 and intermediate or low frequency of methylation of DACH1 or DKK1, respectively. (PMID:25487617)
• DACH1 is a determinant of benign and malignant prostate epithelium cellular growth, migration, and cytokine abundance in vivo. (PMID:25769723)
• DACH1 inhibits aldosterone secretion in human adrenals, and transforming growth factor-beta signaling pathway is activated in DACH1 overexpressed cells and may mediate inhibition of aldosterone secretion in human adrenals. (PMID:25776071)
• results suggest that DACH1 loss of function results in increased cell growth, motility and invasiveness through TGF-beta-mediated EMT, and DACH1 loss of function has important therapeutic implications for targeted therapies of CRC (PMID:25778865)
• Kaplan-Mier analysis of human NSCLC samples demonstrated that high DACH1 mRNA levels predicted favorable prognosis for relapse-free and overall survival. In agreement, high CXCL5 expression predicted a worse prognosis for survival. (PMID:25788272)
• DACH1 expression was reduced in hepatocellular carcinoma even at early stage and associated with tumor progression. Overexpression inhibited HCC cell growth and migration by inactivating the Wnt pathway via GSK3beta phosphorylation to suppress beta-catenin. (PMID:25940701)
• Low DACH1 expression is associated with invasion of lung adenocarcinoma. (PMID:26810067)
• DACH1 expression regulates the pancreatic cancer cell apoptosis. (PMID:27278537)
• Knockdown of DACH1 expression can remarkably enhance the cell apoptosis, restrain the proliferation, migration and invasion of Capan-1 cells. (PMID:27609579)
• DACH1 expression is decreased in glomerulopathy imply a potential role for DACH1 in the this development of human chornic glomerulopathy. (PMID:27888806)
• This study concludes that MiR-217 is the upstream regulator of PGC-1alpha in breast cancer regulation in vitro, possibly independent of DACH1 signaling pathway. (PMID:27916422)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dach1	ENSMUSG00000055639
rattus_norvegicus	Dach1	ENSRNOG00000008834
drosophila_melanogaster	dac	FBGN0005677
caenorhabditis_elegans		WBGENE00000895

Paralogs (1): DACH2 (ENSG00000126733)

Protein

Protein identifiers

Dachshund homolog 1 — Q9UI36 (reviewed: Q9UI36)

All UniProt accessions (3): Q9UI36, A0A994J5V6, A0A994J7Q8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that is involved in regulation of organogenesis. Seems to be a regulator of SIX1, SIX6 and probably SIX5. Corepression of precursor cell proliferation in myoblasts by SIX1 is switched to coactivation through recruitment of EYA3 to the SIX1-DACH1 complex. Transcriptional activation also seems to involve association of CREBBP. Seems to act as a corepressor of SIX6 in regulating proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. Inhibits TGF-beta signaling through interaction with SMAD4 and NCOR1. Binds to chromatin DNA via its DACHbox-N domain.

Subunit / interactions. Interacts with SIX1, SIX6 and EYA3. Interacts with NCOR1 and HDAC3 through its N-terminus. Interacts with SIN3A through its C-terminus. Interacts with SMAD3 and SMAD4.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Isoform 2 is found in brain, heart, kidney, liver, leukocytes and spleen. Isoform 3 is found in liver and heart. Isoform 4 is found in spleen.

Domain organisation. The DACHbox-N/DD1 domain forms a structure containing a DNA binding motif similar to that of the forkhead/winged helix domain.

Miscellaneous. Major.

Similarity. Belongs to the DACH/dachshund family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UI36-1	1	yes
Q9UI36-2	2
Q9UI36-3	3
Q9UI36-4	4

RefSeq proteins (4): NP_001353641, NP_004383, NP_542937, NP_542938 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003380	SKI/SNO/DAC	Domain
IPR009061	DNA-bd_dom_put_sf	Homologous_superfamily
IPR037000	Ski_DNA-bd_sf	Homologous_superfamily
IPR052417	Dachshund_domain	Family

Pfam: PF02437

UniProt features (36 total): region of interest 10, compositionally biased region 9, helix 5, strand 4, splice variant 3, chain 1, coiled-coil region 1, modified residue 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1L8R	X-RAY DIFFRACTION	1.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UI36-F1	58.74	0.26

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): 491

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 344 (showing top): chr13q21, VERHAAK_AML_WITH_NPM1_MUTATED_DN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, TAATAAT_MIR126, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, YANG_BREAST_CANCER_ESR1_LASER_UP, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELL_CYCLE_DNA_REPLICATION, TTTGTAG_MIR520D, GOZGIT_ESR1_TARGETS_DN, GOBP_SUCKLING_BEHAVIOR, TATTATA_MIR374

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), suckling behavior (GO:0001967), regulation of transcription by RNA polymerase II (GO:0006357), respiratory gaseous exchange by respiratory system (GO:0007585), obsolete negative regulation of transcription by competitive promoter binding (GO:0010944), negative regulation of cell migration (GO:0030336), regulation of nuclear cell cycle DNA replication (GO:0033262), type B pancreatic cell proliferation (GO:0044342), negative regulation of DNA-templated transcription (GO:0045892), development of primary female sexual characteristics (GO:0046545), negative regulation of fibroblast proliferation (GO:0048147), negative regulation of cell proliferation involved in contact inhibition (GO:0060244), negative regulation of DNA biosynthetic process (GO:2000279), regulation of DNA-templated transcription (GO:0006355), epithelial cell proliferation (GO:0050673)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), Golgi apparatus (GO:0005794), cytosol (GO:0005829), nuclear speck (GO:0016607), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
negative regulation of cell population proliferation	2
transcription cis-regulatory region binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
feeding behavior	1
multicellular organismal process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
regulation of cell cycle process	1
nuclear DNA replication	1
regulation of DNA-templated DNA replication	1
epithelial cell proliferation	1
negative regulation of RNA biosynthetic process	1
development of primary sexual characteristics	1
female sex differentiation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
contact inhibition	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of DNA metabolic process	1
DNA biosynthetic process	1
regulation of DNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell population proliferation	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
nucleic acid binding	1

Protein interactions and networks

STRING

1172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DACH1	SIX1	Q15475	937
DACH1	EYA1	Q99502	921
DACH1	SMAD4	Q13485	902
DACH1	SIX6	O95475	877
DACH1	PAX3	P23760	782
DACH1	MYF5	P13349	746
DACH1	EYA2	O00167	723
DACH1	SIX4	Q9UIU6	716
DACH1	SIX2	Q9NPC8	676
DACH1	PAX6	P26367	655
DACH1	MYOG	P15173	610
DACH1	EYA3	Q99504	598
DACH1	PAX2	Q02962	577
DACH1	MYOD1	P15172	574
DACH1	ESR1	P03372	552

IntAct

60 interactions, top by confidence:

A	B	Type	Score
CD81	PTGFRN	psi-mi:“MI:0914”(association)	0.790
SMAD4	DACH1	psi-mi:“MI:0915”(physical association)	0.630
SMAD4	DACH1	psi-mi:“MI:2364”(proximity)	0.630
DCK	DGUOK	psi-mi:“MI:0914”(association)	0.620
DACH1	NAGK	psi-mi:“MI:0915”(physical association)	0.550
NAGK	DACH1	psi-mi:“MI:0915”(physical association)	0.550
TRIM44	ODAD3	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
RNPS1	CASC3	psi-mi:“MI:0914”(association)	0.530
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
DACH1	SMAD3	psi-mi:“MI:0915”(physical association)	0.400
SIN3A	DACH1	psi-mi:“MI:0915”(physical association)	0.400
NCOR1	DACH1	psi-mi:“MI:0915”(physical association)	0.400
DACH1	HBB	psi-mi:“MI:0915”(physical association)	0.400
DACH1	UBE2I	psi-mi:“MI:0915”(physical association)	0.370
FOXA2	FOXN2	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
PPM1G	SRP14	psi-mi:“MI:0914”(association)	0.350
SYT2	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
RNPS1	C1orf226	psi-mi:“MI:0914”(association)	0.350

BioGRID (134): DACH1 (Two-hybrid), FGF12 (Two-hybrid), PPIG (Two-hybrid), RNF14 (Two-hybrid), AHCYL1 (Two-hybrid), U2AF2 (Two-hybrid), ZCCHC10 (Two-hybrid), NAGK (Two-hybrid), C1orf35 (Two-hybrid), HBB (Affinity Capture-MS), UBE2I (Two-hybrid), NAGK (Two-hybrid), DACH1 (Proximity Label-MS), NAGK (Two-hybrid), C1orf35 (Two-hybrid)

ESM2 similar proteins: A0A096MJY4, A0A486WWJ9, A2ICN5, A2VDZ3, A4UTP7, A8WL06, B7ZR65, H2LBU8, O89038, P10071, P40791, P55197, P55879, Q02078, Q03413, Q03414, Q06413, Q0VGT2, Q14814, Q2KIA0, Q2MJT0, Q32NP8, Q4VYR7, Q5IS56, Q5R444, Q5REW7, Q5U4X3, Q60929, Q61602, Q63943, Q6DFF5, Q6DIF3, Q6F2E7, Q7ZY13, Q8BUR3, Q8CFN5, Q91660, Q91661, Q9DE25, Q9EPK5

Diamond homologs: H2KY91, Q1XH10, Q80YR3, Q925Q8, Q96NX9, Q9QYB2, Q9UI36, A7M7C7, P84550, P84551, Q1LXZ9, Q2VWA4, Q8BX46

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DACH1	“form complex”	Six1/Dach	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
Infectious disease	8	4.1×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	6	26.8×	2e-05
anatomical structure morphogenesis	6	12.9×	6e-04
transcription by RNA polymerase II	8	8.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4435 predictions. Top by Δscore:

Variant	Effect	Δscore
13:71475700:TCTTA:T	donor_loss	1.0000
13:71475701:CTTA:C	donor_loss	1.0000
13:71475702:TTACC:T	donor_loss	1.0000
13:71475703:TACC:T	donor_loss	1.0000
13:71475704:A:C	donor_loss	1.0000
13:71475705:C:CT	donor_loss	1.0000
13:71475845:TATGG:T	acceptor_gain	1.0000
13:71475847:TGG:T	acceptor_gain	1.0000
13:71475850:C:CC	acceptor_gain	1.0000
13:71479150:T:C	donor_gain	1.0000
13:71479314:CCC:C	acceptor_gain	1.0000
13:71479315:CCCTG:C	acceptor_gain	1.0000
13:71479316:CCTG:C	acceptor_gain	1.0000
13:71479317:C:CA	acceptor_loss	1.0000
13:71489159:T:TC	acceptor_gain	1.0000
13:71508370:T:C	acceptor_gain	1.0000
13:71557154:GACCG:G	acceptor_gain	1.0000
13:71557155:ACCG:A	acceptor_gain	1.0000
13:71557156:CCG:C	acceptor_gain	1.0000
13:71557156:CCGC:C	acceptor_gain	1.0000
13:71557157:CG:C	acceptor_gain	1.0000
13:71557157:CGC:C	acceptor_gain	1.0000
13:71557158:GC:G	acceptor_loss	1.0000
13:71557159:C:CA	acceptor_loss	1.0000
13:71557159:C:CC	acceptor_gain	1.0000
13:71557162:T:C	acceptor_gain	1.0000
13:71557162:T:TC	acceptor_gain	1.0000
13:71557170:C:CT	acceptor_gain	1.0000
13:71557170:C:T	acceptor_gain	1.0000
13:71557171:A:T	acceptor_gain	1.0000

AlphaMissense

4624 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:71475768:C:G	R703P	1.000
13:71475771:C:G	R702P	1.000
13:71475789:A:G	L696P	1.000
13:71475793:C:G	A695P	1.000
13:71475831:A:G	L682P	1.000
13:71475833:C:A	R681S	1.000
13:71475833:C:G	R681S	1.000
13:71479204:A:G	L664P	1.000
13:71479216:A:G	L660P	1.000
13:71479246:A:G	L650P	1.000
13:71479289:C:G	A636P	1.000
13:71479300:G:T	A632D	1.000
13:71479301:C:G	A632P	1.000
13:71479309:A:C	L629W	1.000
13:71479309:A:G	L629S	1.000
13:71479312:A:G	L628P	1.000
13:71479312:A:T	L628Q	1.000
13:71488998:T:G	Q626P	1.000
13:71489001:A:C	I625R	1.000
13:71489001:A:T	I625K	1.000
13:71489003:G:C	N624K	1.000
13:71489003:G:T	N624K	1.000
13:71489004:T:A	N624I	1.000
13:71489010:A:G	L622P	1.000
13:71489010:A:T	L622Q	1.000
13:71489013:A:C	L621R	1.000
13:71489013:A:G	L621P	1.000
13:71489013:A:T	L621H	1.000
13:71681883:C:A	R292S	1.000
13:71681883:C:G	R292S	1.000

dbSNP variants (sampled 300 via entrez): RS1000003351 (13:71528359 T>C), RS1000003975 (13:71796977 AT>A), RS1000016797 (13:71681488 T>A), RS1000019059 (13:71661346 T>C), RS1000025000 (13:71848007 T>C), RS1000026647 (13:71486017 T>A), RS1000030810 (13:71769560 C>G), RS1000033820 (13:71440780 T>C), RS1000045835 (13:71570425 C>A,T), RS1000052822 (13:71576456 T>C), RS1000066650 (13:71817364 C>G,T), RS1000067400 (13:71442842 A>C), RS1000067434 (13:71747349 C>T), RS1000069279 (13:71681078 T>C), RS1000070157 (13:71775569 A>G)

Disease associations

OMIM: gene MIM:603803 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST000649_2	Chronic kidney disease	3.000000e-11
GCST000785_34	Longevity	1.000000e-06
GCST001431_11	Adverse response to lamotrigine and phenytoin	2.000000e-06
GCST001636_3	Obsessive-compulsive disorder	5.000000e-06
GCST001791_19	Urate levels	9.000000e-06
GCST002337_28	Amyotrophic lateral sclerosis (sporadic)	9.000000e-06
GCST002701_13	Verbal declarative memory	4.000000e-06
GCST003372_26	Glomerular filtration rate (creatinine)	6.000000e-08
GCST003401_30	Glomerular filtration rate in non diabetics (creatinine)	1.000000e-07
GCST003485_6	Response to fenofibrate (HDL cholesterol levels)	6.000000e-06
GCST004292_30	Glomerular filtration rate (creatinine)	3.000000e-11
GCST004607_90	Plateletcrit	2.000000e-11
GCST005042_13	Restless legs syndrome	3.000000e-09
GCST005984_37	Glomerular filtration rate	4.000000e-13
GCST005985_41	Creatinine levels	4.000000e-13
GCST005986_18	Blood urea nitrogen levels	2.000000e-12
GCST006446_5	Ulna and radius bone mineral density	2.000000e-06
GCST006627_2	Diastolic blood pressure	4.000000e-11
GCST007203_7	Total cholesterol levels	1.000000e-06
GCST007344_89	Estimated glomerular filtration rate	2.000000e-19
GCST007509_7	Cleft palate	3.000000e-07
GCST007576_205	Chronotype	4.000000e-09
GCST007733_20	Serum uric acid levels	7.000000e-08
GCST007876_79	Estimated glomerular filtration rate	2.000000e-26
GCST007928_37	Medication use (diuretics)	4.000000e-08
GCST008049_46	White blood cell count	7.000000e-09
GCST008058_56	Estimated glomerular filtration rate	5.000000e-28
GCST008059_66	Estimated glomerular filtration rate	1.000000e-23
GCST008060_11	Estimated glomerular filtration rate	3.000000e-08
GCST008062_67	Blood urea nitrogen levels	1.000000e-15

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0007805	HDL cholesterol change measurement
EFO:0007985	platelet crit
EFO:0007933	radius bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0004574	total cholesterol measurement
EFO:0008328	chronotype measurement
EFO:0004761	uric acid measurement
EFO:0009928	Diuretic use measurement
EFO:0010116	choline measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724694 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	Kd	53	nM	MOLIBRESIB
7.10	IC50	80	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179204: Binding affinity against DACH1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0530	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
bisphenol A	affects cotreatment, affects methylation, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	increases methylation, affects methylation	2
Nickel	decreases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
napabucasin	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
nickel chloride	decreases expression	1
diallyl trisulfide	increases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Acetaminophen	affects expression	1
Ethanol	decreases expression	1
Atrazine	decreases expression	1
Cisplatin	decreases expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697477	Binding	Inhibition of DACH1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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