ACD
ACD shelterin complex subunit and telomerase recruitment factor, the group of Shelterin complex
Basic information
Region (hg38): 16:67657512-67660810
Links
Phenotypes
GenCC
Source:
- 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:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Dyskeratosis congenita, autosomal dominant 6; Dyskeratosis congenita, autosomal recessive 7 | AD/AR | Allergy/Immunology/Infectious; Hematologic; Oncologic | Surveillance (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 infections | Allergy/Immunology/Infectious; Hematologic; Oncologic; Neurologic | 25205116; 25233904 |
ClinVar
This is a list of variants' phenotypes submitted to
- 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 317 | 321 | ||||
| missense | 501 | 27 | 528 | |||
| nonsense | 10 | 10 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 18 | 20 | ||||
| splice donor/acceptor (+/-2bp) | 9 | |||||
| Total | 1 | 2 | 542 | 344 | 0 |
Highest pathogenic variant AF is 0.0000068728145
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ACD | protein_coding | protein_coding | ENST00000393919 | 12 | 3299 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.11e-12 | 0.159 | 125685 | 0 | 56 | 125741 | 0.000223 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.486 | 345 | 321 | 1.08 | 0.0000162 | 3398 |
| Missense in Polyphen | 55 | 73.209 | 0.75128 | 931 | ||
| Synonymous | -1.88 | 167 | 139 | 1.20 | 0.00000716 | 1218 |
| Loss of Function | 0.822 | 21 | 25.5 | 0.824 | 0.00000120 | 277 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000579 | 0.000573 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000384 | 0.000381 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000266 | 0.000264 |
| Middle Eastern | 0.000384 | 0.000381 |
| South Asian | 0.0000657 | 0.0000653 |
| Other | 0.000327 | 0.000326 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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