ACD

ACD shelterin complex subunit and telomerase recruitment factor, the group of Shelterin complex

Basic information

Region (hg38): 16:67657512-67660810

Links

ENSG00000102977NCBI:65057OMIM:609377HGNC:25070Uniprot:Q96AP0AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Hoyeraal-Hreidarsson syndrome (Supportive), mode of inheritance: AD
  • hereditary isolated aplastic anemia (Supportive), mode of inheritance: AD
  • dyskeratosis congenita, autosomal dominant 6 (Strong), mode of inheritance: AR
  • dyskeratosis congenita, autosomal dominant 6 (Strong), mode of inheritance: AD
  • dyskeratosis congenita, autosomal dominant 6 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Dyskeratosis congenita, autosomal dominant 6; Dyskeratosis congenita, autosomal recessive 7AD/ARAllergy/Immunology/Infectious; Hematologic; OncologicSurveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; HSCT may be indicated due to manifestations including leukemia and bone marrow failure; Awareness of infectious risk may allow prompt diagnosis and treatment of infectionsAllergy/Immunology/Infectious; Hematologic; Oncologic; Neurologic25205116; 25233904

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACD gene.

  • Inborn_genetic_diseases (743 variants)
  • Dyskeratosis_congenita,_autosomal_dominant_6 (490 variants)
  • not_specified (106 variants)
  • not_provided (50 variants)
  • ACD-related_disorder (16 variants)
  • Long_telomere_syndrome (2 variants)
  • Dyskeratosis_congenita,_autosomal_recessive_7 (2 variants)
  • ACD-related_short_telomere_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACD gene is commonly pathogenic or not. These statistics are base on transcript: NM_001082486.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
317
clinvar
321
missense
501
clinvar
27
clinvar
528
nonsense
10
clinvar
10
start loss
1
1
frameshift
1
clinvar
1
clinvar
18
clinvar
20
splice donor/acceptor (+/-2bp)
1
clinvar
8
clinvar
9
Total 1 2 542 344 0

Highest pathogenic variant AF is 0.0000068728145

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ACDprotein_codingprotein_codingENST00000393919 123299
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.11e-120.1591256850561257410.000223
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.4863453211.080.00001623398
Missense in Polyphen5573.2090.75128931
Synonymous-1.881671391.200.000007161218
Loss of Function0.8222125.50.8240.00000120277

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005790.000573
Ashkenazi Jewish0.000.00
East Asian0.0003840.000381
Finnish0.00009240.0000924
European (Non-Finnish)0.0002660.000264
Middle Eastern0.0003840.000381
South Asian0.00006570.0000653
Other0.0003270.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. Without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by recruiting telomerase to telomeres and increasing its processivity. May play a role in organogenesis. {ECO:0000269|PubMed:15181449, ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:16880378, ECO:0000269|PubMed:17237768, ECO:0000269|PubMed:20231318, ECO:0000269|PubMed:25205116, ECO:0000269|PubMed:25233904}.;
Disease
DISEASE: Dyskeratosis congenita, autosomal dominant, 6 (DKCA6) [MIM:616553]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:25205116}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dyskeratosis congenita, autosomal recessive, 7 (DKCB7) [MIM:616553]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:25233904}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;Regulation of Telomerase (Consensus)

Recessive Scores

pRec
0.134

Intolerance Scores

loftool
0.872
rvis_EVS
-0.6
rvis_percentile_EVS
18.14

Haploinsufficiency Scores

pHI
0.162
hipred
N
hipred_score
0.396
ghis
0.576

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.778

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Acd
Phenotype
integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; neoplasm; pigmentation phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype;

Zebrafish Information Network

Gene name
acd
Affected structure
post-vent region
Phenotype tag
abnormal
Phenotype quality
curved dorsal

Gene ontology

Biological process
telomere maintenance;skeletal system development;urogenital system development;intracellular protein transport;telomere capping;embryonic limb morphogenesis;protection from non-homologous end joining at telomere;telomere assembly;negative regulation of telomere maintenance via telomerase;positive regulation of telomere maintenance via telomerase;segmentation;positive regulation of telomerase activity;positive regulation of single-stranded telomeric DNA binding;protein localization to chromosome, telomeric region;establishment of protein localization to telomere;mitotic telomere maintenance via semi-conservative replication;telomere-telomerase complex assembly
Cellular component
nuclear telomere cap complex;nuclear chromosome, telomeric region;nucleoplasm;nuclear body;shelterin complex
Molecular function
protein binding;telomeric DNA binding;protein-containing complex binding;DNA polymerase binding;protein binding involved in negative regulation of telomere maintenance via telomerase