AHDC1

Chr 1AD

AT-hook DNA binding motif containing 1

Also known as: MRD25, XIGIS

NCBI Gene: 27245ENSG00000126705UniProt: Q5TGY3OMIM: 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
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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ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 51 VUS of 100 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
0.08LOEUF
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 OE0.00 (0.00–0.08)
0≤0.351.4
Missense OE0.75 (0.70–0.79)
0≤0.61.4
Synonymous OE1.03
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
DN
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 · 100% of P/LP variants are LoF · LOEUF 0.08

Literature Evidence

LOFTherefore, we provide further supporting evidence that AHDC1 deletion causes Xia-Gibbs syndrome through a haploinsufficiency mechanism.PMID:30615951

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

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic6
VUS51
Likely Benign39
4
Pathogenic
6
Likely Pathogenic
51
VUS
39
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
0
0
4
Likely Pathogenic
6
0
0
0
6
VUS
0
48
3
0
51
Likely Benign
0
3
0
36
39
Benign
0
0
0
0
0
Total1051336100

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

View in ClinVar →

Protein Context — Lollipop Plot

AHDC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients