AHDC1

Chr 1AD

AT-hook DNA binding motif containing 1

Also known as: MRD25, XIGIS

NCBI Gene: 27245 ENSG00000126705 UniProt: Q5TGY3 OMIM: 615790

The protein contains two AT-hooks that function in DNA binding within the nucleus. Loss-of-function mutations cause Xia-Gibbs syndrome through an autosomal dominant inheritance pattern with haploinsufficiency as the likely pathogenic mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.081 OMIM phenotype

Clinical Summary— AHDC1

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Gene-Disease Validity (ClinGen)

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.08LOEUF

pLI 1.000

Z-score 5.78

OE 0.00 (0.00–0.08)

Highly constrained

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

Missense Constraint?

2.86Z-score

OE missense 0.75 (0.70–0.79)

764 obs / 1021.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.08)

0≤0.351.4

Missense OE?0.75 (0.70–0.79)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 0 / 38.9Missense obs/exp: 764 / 1021.1Syn Z: -0.57

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveAHDC1-related Xia-Gibbs syndromeLOFAD

This gene — mechanism propensity

0.15100th %ile

GOF

0.2098th %ile

LOF

0.91top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.08 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFTherefore, we provide further supporting evidence that AHDC1 deletion causes Xia-Gibbs syndrome through a haploinsufficiency mechanism.1

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

References