DIDO1

Chr 20

death inducer-obliterator 1

Also known as: BYE1, C20orf158, DATF-1, DATF1, DIDO2, DIDO3, DIO-1, DIO1

NCBI Gene: 11083 ENSG00000101191 UniProt: Q9BTC0 OMIM: 604140

The DIDO1 protein functions as a transcription factor and tumor suppressor that is required for early embryonic stem cell development. Mutations cause intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, which follows an autosomal dominant inheritance pattern. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Apoptosis, a major form of cell death, is an efficient mechanism for eliminating unwanted cells and is of central importance for development and homeostasis in metazoan animals. In mice, the death inducer-obliterator-1 gene is upregulated by apoptotic signals and encodes a cytoplasmic protein that translocates to the nucleus upon apoptotic signal activation. When overexpressed, the mouse protein induced apoptosis in cell lines growing in vitro. This gene is similar to the mouse gene and therefore is thought to be involved in apoptosis. Alternatively spliced transcripts have been found for this gene, encoding multiple isoforms. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— DIDO1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

160 VUS of 228 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 7.31

OE 0.10 (0.06–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.10Z-score

OE missense 0.92 (0.88–0.96)

1292 obs / 1408.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.06–0.19)

0≤0.351.4

Missense OE?0.92 (0.88–0.96)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 8 / 77.3Missense obs/exp: 1292 / 1408.0Syn Z: -2.03

This gene — mechanism propensity

0.18100th %ile

GOF

0.1699th %ile

LOF

0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

228 submitted variants in ClinVar

ClinVar

Classification Summary

VUS160

Likely Benign25

Benign10

Conflicting1

160

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	160	0	0	160
Likely Benign	0	16	0	9	25
Benign	0	4	0	6	10
Conflicting	—				1
Total	0	180	0	15	196

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

32 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap DIDO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →