ANKRD11

  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ANKRD11 (HGNC:21316) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
ankyrin repeat domain containing 11
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
LZ16, T13, ANCO1, ANCO-1
%HI
75.55(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.11(Read more about gnomAD LOEUF score)
Cytoband
16q24.3
Genomic Coordinates
GRCh37/hg19: chr16:89334038-89556969 NCBI Ensembl UCSC
GRCh38/hg38: chr16:89267630-89490561 NCBI Ensembl UCSC
MANE Select Transcript
NM_013275.6 ENST00000301030.10 (Read more about MANE Select)
Function
Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells (By similarity). May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation (PubMed:15184363). Has a role in proliferation and development of cortical neural precursors (PubMed:25556659). May also regulate bone homeostasis (By similarity). {ECO:0000250|UniProtKB:E9Q4F7, ECO:0000269|PubMed:15184363, ECO:0000269|PubMed:255... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-36318
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
06/14/2022

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 21782149
    Sirmaci et al. 2011: In a study of ten families from Turkey and Italy with a clinical diagnosis of KBG syndrome, the authors identified a heterozygous variant (c.7570-1G>C (p.Glu2524_Lys2525del) in the ANKRD11 gene by whole exome sequencing segregating with the phenotype within a multiplex family and a heterozygous de novo variant (c.2305delT (p.Ser769GlnfsX8) in ANKRD11 in a simplex family. Sanger sequencing of ANKRD11 for the remaining 8 families revealed three additional heterozygous truncating mutations in three simplex families, including one nonsense variant, c.7189C>T (p.Gln2397X). All of these were determined to be de novo. All five ANKRD11 variants were negative in ethnicity-matched controls. Sanger sequencing as well as CNV analysis of ANKRD11 via quantitative PCR remained negative in the five other probands.
  • PUBMED: 35330407
    Gao F et al., 2022: the author reported 13 new Chinese cases (7 males and 6 females) ranging from 7 months to 15 years old. Whole exome sequencing showed eight de novo loss of function variants, two of unknown parental inheritance, one de novo missense variant (c.7832A > T p.H2611L) and two other missense variants (c.5519C > T (p.A1840V), c.6122T > G p.V2041G) of each maternal and paternal inheritance. The loss of function variants include seven frameshift variations and three nonsense variations. Five are novel variants: c.3562C > T (p.R1188*), c.4911delT (p.P1638Lfs*48), c.5659C > T (p.Q1887*), c.2262dupA (p.E755Rfs*27) and c.6528_6538del(p.G2177Hfs*5). Three of the variants have been previously reported: c.2398_2401del (p.E800Nfs*62), c.1801C > T (p.R601*), and c.1903_1907del (p.K635Qfs*26). This author also reviewed genotype and phenotype relationship among 235 KBGS patients reported in literature with ANKRD11 gene variation, 218 cases of ANKRD11 truncated variation and 13 case of missense variation. Significant differences between the two groups of patients in global developmental delays and intellectual disability/learning difficulties were demonstrated.
  • PUBMED: 28422132
    Novara F et al. 2017: the author reported 12 new KGBS cases with deletions of 16q24.2q24.3 and reviewed 13 previously reported cases. One intragenic deletion (Isrie M et al., 2012; PMID: 21654729.) and one intragenic duplication are included (Crippa M et al., 2015; PMID: 25838844). The rest of the cases with deletions involved additional genes beyond just ANKRD11 (ranging from 137 kb to 2 Mb). By comparing the clinical and genetic features of these 12 patients with those previously reported, these authors showed that the severity of the neurological phenotype and the frequency of congenital heart defects characterize the deletions that, besides ANKRD11, contain ZFPM1, CDH15 and ZNF778 as well. Moreover, the presence of thrombocytopenia and astigmatism should be taken into account to distinguish between 16q24 microdeletion syndrome and KBG syndrome.
HI Evidence Comments:
KBG syndrome is characterized by macrodontia of upper central incisors, distinctive craniofacial features such as triangular face, prominent nasal bridge, thin upper lip and synophrys; skeletal findings including short stature, delayed bone age, and costovertebral anomalies; and developmental delay/intellectual disability sometimes associated with seizures and EEG abnormalities. The condition was named KBG syndrome after the initials of the last names of three original families reported in 1975 (Swols DM et al., 2017: PMID: 29258554.).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000016.9) (NC_000016.10)