DACH2

Summary

DACH2 (dachshund family transcription factor 2, HGNC:16814) is a protein-coding gene on chromosome Xq21.2, encoding Dachshund homolog 2 (Q96NX9). Transcription factor that is involved in regulation of organogenesis.

This gene is one of two genes which encode a protein similar to the Drosophila protein dachshund, a transcription factor involved in cell fate determination in the eye, limb and genital disc of the fly. The encoded protein contains two characteristic dachshund domains: an N-terminal domain responsible for DNA binding and a C-terminal domain responsible for protein-protein interactions. This gene is located on the X chromosome and is subject to inactivation by DNA methylation. The encoded protein may be involved in regulation of organogenesis and myogenesis, and may play a role in premature ovarian failure. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 117154 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ovarian failure (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 124 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 2 (q < 0.05)
• MANE Select transcript: NM_053281
• Notable: 124 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16814
Approved symbol	DACH2
Name	dachshund family transcription factor 2
Location	Xq21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000126733
Ensembl biotype	protein_coding
OMIM	300608
Entrez	117154

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

MANE Select: ENST00000373125

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 5: 1

ENST00000373125, ENST00000373131, ENST00000461604, ENST00000484479, ENST00000506327, ENST00000508860, ENST00000510272

RefSeq mRNA: 3 — MANE Select: NM_053281 NM_001139514, NM_001139515, NM_053281

CCDS: CCDS14455, CCDS48140, CCDS55457

Canonical transcript exons

ENST00000373125 — 12 exons

Exon	Start	End
ENSE00001634305	86714548	86714720
ENSE00003473900	86832106	86832602
ENSE00003478843	86514279	86514391
ENSE00003540694	86813130	86813277
ENSE00003554728	86376824	86376862
ENSE00003555518	86816034	86816099
ENSE00003562053	86695021	86695179
ENSE00003620452	86739747	86739882
ENSE00003660790	86651036	86651167
ENSE00003663002	86812856	86813004
ENSE00003671089	86814688	86814834
ENSE00003844511	86148451	86149108

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 92.49.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0957 / max 301.4259, expressed in 312 samples.

Highest expression (Bgee): endothelial cell, Brodmann (1909) area 23, middle temporal gyrus, entorhinal cortex, oviduct epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DACH2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Minor Salivary Gland	eqtl	3.7e-06	+0.30	X:86310469:C:T
Adipose Subcutaneous	eqtl	2.4e-05	+0.22	X:86834223:C:G
Brain Frontal Cortex BA9	eqtl	3.0e-05	+0.18	X:86798376:C:T
Thyroid	eqtl	2.0e-03	+0.43	X:86052596:A:G
Brain Cortex	eqtl	1.4e-02	+0.10	X:86783420:C:T
Skin Sun Exposed Lower leg	eqtl	1.6e-02	+0.19	X:87000071:C:CA
Brain Cortex	sqtl	2.0e-02	+0.35	X:86844138:A:G
Pituitary	eqtl	2.5e-02	-1.62	X:85275589:G:T
Nerve Tibial	eqtl	2.6e-02	+0.16	X:86834223:C:G
Lung	eqtl	2.7e-02	-0.17	X:86941848:G:A
Colon Transverse	eqtl	2.7e-02	+0.16	X:86926136:T:G
Kidney Cortex	eqtl	3.8e-02	+0.30	X:86540346:A:C
Brain Frontal Cortex BA9	sqtl	4.5e-02	+1.41	X:85790423:A:C
Brain Cerebellum	eqtl	4.6e-02	+0.30	X:86762776:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
196849	1.0169	262
196852	0.9759	90
196850	0.0575	20
196851	0.0455	15

Top tissues by expression

showing 100 of 225 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	92.49	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.86	gold quality
middle temporal gyrus	UBERON:0002771	87.52	gold quality
entorhinal cortex	UBERON:0002728	85.07	gold quality
oviduct epithelium	UBERON:0004804	84.48	gold quality
superior frontal gyrus	UBERON:0002661	82.47	gold quality
postcentral gyrus	UBERON:0002581	79.89	silver quality
nucleus accumbens	UBERON:0001882	79.10	gold quality
ventricular zone	UBERON:0003053	78.54	gold quality
Ammon’s horn	UBERON:0001954	78.40	gold quality
prefrontal cortex	UBERON:0000451	77.77	gold quality
parietal lobe	UBERON:0001872	77.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.46	gold quality
temporal lobe	UBERON:0001871	77.38	gold quality
cerebral cortex	UBERON:0000956	77.16	gold quality
islet of Langerhans	UBERON:0000006	76.75	gold quality
anterior cingulate cortex	UBERON:0009835	76.54	gold quality
frontal cortex	UBERON:0001870	76.33	gold quality
neocortex	UBERON:0001950	76.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.93	gold quality
hypothalamus	UBERON:0001898	75.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	74.97	gold quality
caudate nucleus	UBERON:0001873	74.24	gold quality
amygdala	UBERON:0001876	73.80	gold quality
forebrain	UBERON:0001890	73.11	gold quality
putamen	UBERON:0001874	72.38	gold quality
primary visual cortex	UBERON:0002436	71.78	gold quality
right uterine tube	UBERON:0001302	71.69	gold quality
right frontal lobe	UBERON:0002810	71.69	gold quality
ganglionic eminence	UBERON:0004023	71.36	gold quality
metanephros	UBERON:0000081	70.59	gold quality
brain	UBERON:0000955	68.20	gold quality
cortical plate	UBERON:0005343	67.71	gold quality
stromal cell of endometrium	CL:0002255	66.99	gold quality
occipital lobe	UBERON:0002021	66.76	gold quality
adrenal tissue	UBERON:0018303	66.28	gold quality
fallopian tube	UBERON:0003889	66.06	gold quality
metanephros cortex	UBERON:0010533	64.64	gold quality
superior vestibular nucleus	UBERON:0007227	63.14	gold quality
substantia nigra	UBERON:0002038	62.03	gold quality
midbrain	UBERON:0001891	61.03	gold quality
buccal mucosa cell	CL:0002336	58.51	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	58.10	gold quality
corpus epididymis	UBERON:0004359	58.07	silver quality
tibialis anterior	UBERON:0001385	56.05	silver quality
substantia nigra pars compacta	UBERON:0001965	55.96	gold quality
lower lobe of lung	UBERON:0008949	55.75	silver quality
pancreas	UBERON:0001264	55.61	gold quality
cauda epididymis	UBERON:0004360	55.25	silver quality
caput epididymis	UBERON:0004358	54.96	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
cerebellar vermis	UBERON:0004720	54.14	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.63	gold quality
kidney	UBERON:0002113	53.53	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
pons	UBERON:0000988	53.11	silver quality
adult mammalian kidney	UBERON:0000082	53.08	gold quality
ileal mucosa	UBERON:0000331	52.98	gold quality
medulla oblongata	UBERON:0001896	51.79	silver quality
pancreatic ductal cell	CL:0002079	51.60	silver quality
myocardium	UBERON:0002349	50.25	gold quality
deltoid	UBERON:0001476	50.00	silver quality
cortex of kidney	UBERON:0001225	49.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	48.90	silver quality
adenohypophysis	UBERON:0002196	48.22	gold quality
calcaneal tendon	UBERON:0003701	47.91	gold quality
quadriceps femoris	UBERON:0001377	47.51	gold quality
endocervix	UBERON:0000458	47.34	gold quality
body of uterus	UBERON:0009853	47.17	gold quality
lateral globus pallidus	UBERON:0002476	47.14	silver quality
pituitary gland	UBERON:0000007	47.04	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
ovary	UBERON:0000992	46.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.74	gold quality
spinal cord	UBERON:0002240	46.20	gold quality
urinary bladder	UBERON:0001255	46.07	gold quality
prostate gland	UBERON:0002367	46.07	gold quality
left ovary	UBERON:0002119	45.80	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
corpus callosum	UBERON:0002336	45.36	silver quality
duodenum	UBERON:0002114	45.30	gold quality
smooth muscle tissue	UBERON:0001135	45.23	gold quality
tendon	UBERON:0000043	44.90	silver quality
muscle tissue	UBERON:0002385	44.86	silver quality
body of pancreas	UBERON:0001150	44.76	gold quality
right ovary	UBERON:0002118	44.59	gold quality
stomach	UBERON:0000945	44.42	gold quality
left uterine tube	UBERON:0001303	43.91	gold quality
subcutaneous adipose tissue	UBERON:0002190	43.79	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
anatomical system	UBERON:0000467	43.50	gold quality
material anatomical entity	UBERON:0000465	43.47	gold quality
multicellular organism	UBERON:0000468	43.47	gold quality
uterus	UBERON:0000995	43.46	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
thymus	UBERON:0002370	43.17	gold quality
female reproductive system	UBERON:0000474	42.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-2	yes	8804.15
E-ANND-3	yes	4.57

HPA expression

RNA tissue specificity: Tissue enhanced

54 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	7.0
Postcentral gyrus	tissue	6.8
Hippocampus	tissue	6.2	medium
Locus coeruleus	tissue	5.6
Fallopian tube	tissue	3.6	medium
Epididymis	tissue	3.5	not detected
Retina	tissue	1.8
Ventral forebrain	tissue	1.6
Hypothalamus	tissue	1.4
Amygdala	tissue	1.1
Septum	tissue	1.1
Cerebral cortex	tissue	1.0	high
Superior colliculi	tissue	1.0
Retrosplenial and cingulate cortex	tissue	1.0
Periaqueductal gray	tissue	1.0
Retrosplenial cortex	tissue	1.0
Prefrontal cortex	tissue	0.9
Pons	tissue	0.9
Motor cortex	tissue	0.9
Medulla oblongata	tissue	0.9
Basal ganglia	tissue	0.8	medium
Kidney	tissue	0.8	not detected
Insular cortex	tissue	0.8
Corpus callosum	tissue	0.7
Midbrain	tissue	0.6
Cerebellum	tissue	0.6	high
Spinal cord	tissue	0.6
Hippocampal formation	tissue	0.6
Olfactory bulb	tissue	0.6
Temporal cortex	tissue	0.6
Pituitary gland	tissue	0.5
Putamen	tissue	0.5
Choroid plexus	tissue	0.5
Substantia nigra	tissue	0.5
Entorhinal cortex	tissue	0.5
Somatosensory cortex	tissue	0.5
Occipital cortex	tissue	0.5
Stomach 1	tissue	0.4	not detected
Thalamus	tissue	0.4
Prostate	tissue	0.4	not detected
Ovary	tissue	0.3	not detected
Endometrium 1	tissue	0.3	not detected
Frontal cortex	tissue	0.3
Small intestine	tissue	0.3	not detected
Caudate putamen	tissue	0.3
Cervix	tissue	0.2	not detected
Urinary bladder	tissue	0.2	not detected
Pancreas	tissue	0.2	not detected
Duodenum	tissue	0.2	not detected
Seminal vesicle	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Thyroid gland	tissue	0.1	not detected
Lung	tissue	0.1	not detected
Adrenal gland	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Ventromedial nucleus (13.5), Arcuate nucleus (13.1), Perirhinal gyrus (9.6), Hippocampus, CA1 (9.2), Olfactory area (8.5).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
HELT
MYOG	Repression

Upstream regulators (CollecTRI, top): MYOG

miRNA regulators (miRDB)

Targeting DACH2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 49 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4756-3P	99.62	66.30	1319

Functional genomics

Regional missense constraint (gnomAD)

ENST00000373125 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
X:86,148,621–86,149,020	99 / 114.3	0.87	no
X:86,149,021–86,376,824	7 / 24.1	0.29	yes (p 5.0e-04)
X:86,376,825–86,832,152	363 / 334.4	1.09	no

Literature-anchored findings (GeneRIF, showing 3)

• Most X;autosome translocations associated with premature ovarian failure do not interrupt X-linked genes. Only one of the six breakpoints disrupts a gene, DACH2. (PMID:12438735)
• Exome sequencing in two brothers with distinct phenotype including congenital language disorder, growth retardation, intellectual disability and urinary and fecal incontinence, identifies missense mutations in ABCD1 and DACH2. (PMID:25234129)
• DACH2 is an independent prognostic marker that can be used at initial diagnosis of urothelial carcinoma of the bladder to identify patients who have a high potential to develop metastasis. (PMID:25744029)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dacha	ENSDARG00000010132
danio_rerio	dachb	ENSDARG00000034785
mus_musculus	Dach2	ENSMUSG00000025592
rattus_norvegicus	Dach2	ENSRNOG00000004869
drosophila_melanogaster	dac	FBGN0005677
caenorhabditis_elegans		WBGENE00000895

Paralogs (1): DACH1 (ENSG00000276644)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1890446) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 16 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
enlarged heart	1
abnormal urinary bladder morphology	1
abnormal spleen morphology	1
enlarged spleen	1
small spleen	1
enlarged lymph nodes	1
small seminal vesicle	1
anophthalmia	1
abnormal seminal vesicle morphology	1
abnormal eye morphology	1
abnormal kidney morphology	1
small lymph nodes	1
abnormal lymph node morphology	1
increased eosinophil cell number	1
enlarged urinary bladder	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KLHL4	protein-coding	56062
CHM	protein-coding	1121
MIR361	ncRNA	494323

Protein

Protein identifiers

Dachshund homolog 2 — Q96NX9 (reviewed: Q96NX9)

All UniProt accessions (4): D6REJ4, D6RFG7, H0Y912, Q96NX9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that is involved in regulation of organogenesis. Seems to be a regulator for SIX1 and SIX6. Seems to act as a corepressor of SIX6 in regulating proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. Is recruited with SIX6 to the p27Kip1 promoter in embryonal retina. SIX6 corepression also seems to involve NCOR1, TBL1, HDAC1 and HDAC3. May be involved together with PAX3, SIX1, and EYA2 in regulation of myogenesis. In the developing somite, expression of DACH2 and PAX3 is regulated by the overlying ectoderm, and DACH2 and PAX3 positively regulate each other’s expression. Probably binds to DNA via its DACHbox-N domain.

Subunit / interactions. Interacts with SIX6 and EYA2.

Subcellular location. Nucleus.

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

Similarity. Belongs to the DACH/dachshund family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96NX9-1	1	yes
Q96NX9-2	2
Q96NX9-3	3
Q96NX9-4	4

RefSeq proteins (3): NP_001132986, NP_001132987, NP_444511* (*=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	Family

Pfam: PF02437

UniProt features (13 total): region of interest 5, splice variant 4, compositionally biased region 2, chain 1, coiled-coil region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NX9-F1	62.69	0.32

Human Protein Atlas

Protein class: Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 84 (showing top): BENPORATH_ES_WITH_H3K27ME3, NFKB_C, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_FEMALE_SEX_DIFFERENTIATION, GOBP_SEX_DIFFERENTIATION, AACTTT_UNKNOWN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, CDPCR3HD_01, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, OSF2_Q6, SMAD4_Q6, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, SMAD_Q6, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_DN

GO Biological Process (2): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (3): 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 (GO:0003677)

GO Cellular Component (2): nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

12 GO namespaces:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
gene expression	1
RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

showing 15 of 588 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DACH2	POF1B	Q8WVV4	666
DACH2	SATL1	Q86VE3	510
DACH2	MYOG	P15173	509
DACH2	EYA2	O00167	505
DACH2	DIAPH2	O60879	498
DACH2	XPNPEP2	O43895	472
DACH2	HDAC4	P56524	467
DACH2	APOOL	Q6UXV4	456
DACH2	KLHL4	Q9C0H6	431
DACH2	ZNF711	Q9Y462	419
DACH2	SIX1	Q15475	407
DACH2	NXF5	Q9H1B4	388
DACH2	EYA1	Q99502	385
DACH2	EYA3	Q99504	378
DACH2	TM7SF3	Q9NS93	368

IntAct

Human interaction partners of DACH2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
ATP6V1G1	physical association	0.400	1
CFTR	physical association	0.370	1
IRF9	physical association	0.370	1
TSC1	physical association	0.370	1
GYG2	association	0.350	1
TRIM26	association	0.350	1

BioGRID (25 interactions; top human partners by supporting records): CD2AP (Affinity Capture-MS; 2 records), DACH1 (Affinity Capture-MS; 2 records), GYG2 (Affinity Capture-MS; 2 records), TRIM26 (Affinity Capture-MS; 2 records), TRIM44 (Affinity Capture-MS; 2 records), ATP6V1G1 (Cross-Linking-MS (XL-MS)), CFTR (PCA), CPVL (Affinity Capture-MS), DDX39A (Affinity Capture-RNA), FASN (Positive Genetic), IRF9 (Two-hybrid), NUDT21 (Affinity Capture-RNA), SALL1 (Proximity Label-MS), SPPL3 (Positive Genetic), TNKS (Proximity Label-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
DACH2	“down-regulates quantity by repression”	MYOG	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for DACH2: 124 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	5
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 2,974):

Position(s)	Effect	Δscore	Sites
X:86149109	donor_loss	1.0000	3
X:86514277–86514278	acceptor_loss	1.0000	5
X:86594508	donor_gain	1.0000
X:86651034–86651035	acceptor_loss	1.0000	6
X:86651168	donor_loss	1.0000	2
X:86714546–86714547	acceptor_loss	1.0000	5
X:86714721–86714722	donor_loss	1.0000	4
X:86739739	acceptor_gain	1.0000
X:86739745–86739746	acceptor_loss	1.0000	6
X:86739883–86739884	donor_loss	1.0000	5

AlphaMissense

1,256 missense substitutions predicted likely pathogenic (of 3,943 scored), across 291 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M340	9	0.859	0.990
H107	8	0.996	1.000
N142	8	0.994	1.000
D158	8	0.994	0.998
F81	8	0.992	1.000
F98	8	0.991	1.000
F152	8	0.989	1.000
F95	8	0.979	1.000
D151	8	0.977	0.997
F316	8	0.957	0.994
N461	8	0.918	0.993
H321	8	0.914	0.989
M335	8	0.886	0.989
M337	8	0.870	0.983
H101	8	0.862	0.939
C90	7	0.999	1.000
C123	7	0.999	1.000
C144	7	0.999	1.000
C159	7	0.996	1.000
K112	7	0.987	1.000

HPA cancer prognostics

RNA cancer specificity: Not detected

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000613

Disease associations

OMIM: gene MIM:300608 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
primary ovarian failure	Limited	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Primary ovarian insufficiency	amber

Mondo (1): primary ovarian failure (MONDO:0005387)

GWAS associations

2 associations:

Study	Trait	p-value
GCST003991_20	Childhood ear infection	4e-7
GCST009391_320	Metabolite levels	2e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0010433	triacylglycerol 56:6 measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
Aflatoxin B1	affects expression, decreases methylation, increases methylation	3
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
methyleugenol	decreases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
manganese chloride	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Manganese	increases expression	1
Tretinoin	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 75 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	Phase 2/3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	Phase 2/3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	Phase 1/2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	Phase 1/2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	Phase 1/2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	Phase 1/2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	Phase 1/2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	Phase 1/2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	Phase 1/2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	Phase 1/2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	Phase 1/2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	Phase 1/2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	Phase 1/2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	Phase 1/2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	Phase 1/2	COMPLETED	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	Early Phase 1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	Early Phase 1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	Early Phase 1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00295087	Not specified	COMPLETED	X-Chromosome Inactivation Status and Premature Ovarian Failure
NCT00417157	Not specified	COMPLETED	Modified Natural Cycle Offers a Chance of Pregnancy in Patients With Poor Response and High Basal FSH
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT00780897	Not specified	UNKNOWN	Premature Ovarian Failure (Genetic and Physiopathologic Analysis)
NCT01187524	Not specified	TERMINATED	The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
NCT01411644	Not specified	UNKNOWN	Pheno- & Genotyping POF (WHO III)
NCT02086318	Not specified	UNKNOWN	A New Algorithm to Predict Ovarian Age
NCT02467231	Not specified	ACTIVE_NOT_RECRUITING	Ovarian Reserve After Cancer: Longitudinal Effects
NCT02696889	Not specified	COMPLETED	Rejuvenation of Premature Ovarian Failure With Stem Cells
NCT02779374	Not specified	TERMINATED	Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency
NCT03207412	Not specified	UNKNOWN	Human Amniotic Epithelial Cells Treatment for Ovarian Insufficiency
NCT03381300	Not specified	ACTIVE_NOT_RECRUITING	Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
NCT03412487	Not specified	UNKNOWN	Ovarian Histopathology and Laparoscopic Assessment of Premature Ovarian Failure
NCT03474120	Not specified	UNKNOWN	Prospective Genetic Study in Patients With Ovarian Insufficiency
NCT03480412	Not specified	UNKNOWN	Second Step Protocol in Poor Ovarian Responder (POR)
NCT03840824	Not specified	COMPLETED	Blood Spot Self-administered Test and Assay
NCT03861715	Not specified	UNKNOWN	Single Follicular Dexarelix for LH Suppression During Ovarian Stimulation in Oocyte Donors.
NCT03924648	Not specified	COMPLETED	Endocan Levels in Women With Premature Ovarian Insufficiency
NCT04149028	Not specified	COMPLETED	Platelet Rich Plasma Injection Into Ovary of Patients With Premature Ovarian Insufficiency
NCT04189406	Not specified	UNKNOWN	Turner Syndrome Minipuberty Study