GeneBe

AHDC1

protein-coding

AT-hook DNA binding motif containing 1

Gene summary

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]

MANE transcript

NM_001371928.1

Inheritance

AD

ClinVar variants

P:193U:618B:682

Top phenotype

Xia-Gibbs syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr1:27,534,035-27,604,431

External References & Databases

Ensembl (ENSG00000126705)NCBI Gene (27245)OMIM (615790)HGNC:25230GenCCUniProt (Q5TGY3)AlphaFoldClinVar (AHDC1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~70.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014358

Submitter: Illumina

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014358

Submitter: Labcorp Genetics (formerly Invitae)

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014358

Submitter: G2P

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014358

Submitter: Orphanet

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014358

Submitter: PanelApp Australia

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014358

Submitter: ClinGen

AHDC1 was first reported in relation to autosomal dominant AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome (also reported as Xia-Gibbs syndrome) in 2014 (Xia, et al., PMID: 24791903). At least 35 unique variants (e.g. missense, nonsense, frameshift, large deletion, complex rearrangement, etc.) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data. Variants in this gene have been reported in at least 40 probands in 9 publications (PMIDs: 29696776, 27148574, 24791903, 30152016, 32256298, 31182893, 29230160, 33372375, 30622101). Twelve variants (nonsense, frameshift) that have been reported in 14 probands in 6 publications (PMIDs: 27148574, 31182893, 32256298, 29230160, 24791903, 30152016) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is haploinsufficiency (PMIDs: 24791903, 27148574). In summary, AHDC1 is definitively associated with autosomal dominant AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen (Intellectual Disability and Autism Gene Curation Expert Panel) Working Group on the meeting date 11/16/2021 (SOP Version 8).

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014358

Submitter: Illumina

Clinical Genomic Database (CGD)

Xia-Gibbs syndromeAD

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24791903Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AHDC1 variants in ClinVar

22 Conditions Cataloged
not providedTotal: 1189
Inborn genetic diseasesTotal: 289
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndromeTotal: 242
AHDC1-related disorderTotal: 126
not specifiedTotal: 84
Intellectual disabilityTotal: 16
See casesTotal: 7
Neurodevelopmental abnormalityTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001371928.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
6
clinvar
392
clinvar
19
clinvar
 417
missense
6
clinvar
601
clinvar
255
clinvar
16
clinvar
 878
nonsense
37
clinvar
14
clinvar
1
clinvar
 52
start loss
0
frameshift
97
clinvar
39
clinvar
7
clinvar
 143
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total13459618647351493

Highest pathogenic variant AF is 0.000011213402

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001371928.1RefSeqNP_001358857.11MANE Select
ENST00000673934.1EnsemblENSP00000501218.11MANE Select
NM_001029882.3RefSeqNP_001025053.11Standard
ENST00000247087.10EnsemblENSP00000247087.41Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Mesodermal Commitment Pathway

Molecular Function

  • DNA binding

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000374011
Coding exons
1
Length
70397
Individuals with no LoFs
125148
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
125149
p
0.00000400
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.867641.02e+30.7480.000072710021
Missense (PolyPhen)85120.670.70441043
Synonymous-0.5674884721.030.00003513692
Loss of Function5.78038.90.000.00000231434

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Disease
DISEASE: Mental retardation, autosomal dominant 25 (MRD25) [MIM:615829]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD25 additional features include mild dysmorphism, hypotonia, delayed psychomotor development with absent or poor expressive language, hypoplasia of the corpus callosum, simplified gyral pattern, and delayed myelination. {ECO:0000269|PubMed:24791903}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool
0.0110
RVIS EVS
-1.1
RVIS percentile EVS
6.98

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Indispensability pred.
E
Indispensability score
0.526

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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