DACH1

Chr 13

dachshund family transcription factor 1

Also known as: DACH

NCBI Gene: 1602 ENSG00000276644 UniProt: Q9UI36

DACH1 encodes a chromatin-associated transcription factor that regulates organogenesis and cell fate determination during development, including control of precursor cell proliferation and TGF-beta signaling pathways. Mutations cause autosomal dominant developmental disorders affecting multiple organ systems. This gene is highly constrained against loss-of-function variants, indicating that such mutations are typically severe.

ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Sep 2009]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.14LOEUF

pLI 1.000

Z-score 4.36

OE 0.00 (0.00–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.19Z-score

OE missense 0.67 (0.60–0.75)

238 obs / 353.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.14)

0≤0.351.4

Missense OE?0.67 (0.60–0.75)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 0 / 22.1Missense obs/exp: 238 / 353.6Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in DACH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

918 rare PASS variants

Rare truncating (LoF)

1 in 3,500

59 rare PASS variants

Rare synonymous (reference)

1 in 150

427 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DACH1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 90	1 in 3,500
South Asian	~43k	1 in 67	1 in 4,500
Remaining (unassigned)	~30k	1 in 86	1 in 3,300
European (Finnish)	~27k	1 in 190	1 in 4,800
Admixed American	~22k	1 in 53	1 in 3,600
African / African American	~21k	1 in 83	1 in 2,200
East Asian	~20k	1 in 76	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 310	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 100	≈ 1 in 1,100

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 11 coding exons well covered in gnomAD exomes; exons 1, 11 marginal. Genomes: all 11.? see exons ↓