ANKRD11

ankyrin repeat domain containing 11, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 16:89267629-89490561

Links

ENSG00000167522 ∙ NCBI:29123 ∙ OMIM:611192 ∙ HGNC:21316 ∙ Uniprot:Q6UB99 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• KBG syndrome (Definitive), mode of inheritance: AD
• KBG syndrome (Definitive), mode of inheritance: AD
• KBG syndrome (Definitive), mode of inheritance: AD
• KBG syndrome (Supportive), mode of inheritance: AD
• congenital heart defects, multiple types (Limited), mode of inheritance: AD
• KBG syndrome (Strong), mode of inheritance: AD
• KBG syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
KBG syndrome	AD	General	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	Craniofacial; Dental; Musculoskeletal; Neurologic	15523620; 15378538; 21782149; 22307766; 25125236

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANKRD11 gene.

• KBG syndrome (1243 variants)
• not provided (885 variants)
• Inborn genetic diseases (538 variants)
• not specified (57 variants)
• ANKRD11-related condition (29 variants)
• Global developmental delay (17 variants)
• Intellectual disability (16 variants)
• See cases (8 variants)
• Neurodevelopmental disorder (6 variants)
• Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis (6 variants)
• Rare genetic intellectual disability (5 variants)
• Developmental disorder (3 variants)
• Autism spectrum disorder (2 variants)
• Abnormality of the nervous system (2 variants)
• Macrocephaly;Global developmental delay;Seizure;Atypical behavior;Hand tremor (1 variants)
• Abnormal facial shape;Seizure;Conductive hearing impairment;Delayed speech and language development;Global developmental delay (1 variants)
• Neurodevelopmental delay (1 variants)
• 8 conditions (1 variants)
• Seizure (1 variants)
• Sudden unexplained death in childhood (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANKRD11 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	441	35	482
missense	2	22	651	157	29	861
nonsense	88	26				114
start loss						0
frameshift	205	57	3			265
inframe indel	1	1	37	1		40
splice donor/acceptor (+/-2bp)	11	4	2			17
splice region	2		13	12		27
non coding	2		14	78	50	144
Total	309	110	713	677	114

Highest pathogenic variant AF is 0.00000658

Variants in ANKRD11

This is a list of pathogenic ClinVar variants found in the ANKRD11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-89268198-G-C			Benign (Apr 04, 2020)
16-89268210-C-T			Benign (Apr 13, 2020)
16-89268213-G-C			Benign (Apr 13, 2020)
16-89268253-G-A			Likely benign (Aug 31, 2020)
16-89268271-G-A			Likely benign (Feb 13, 2020)
16-89268320-G-A			Benign (Aug 31, 2018)
16-89268470-C-T			Benign (Mar 01, 2022)
16-89268491-A-G		Global developmental delay	Uncertain significance (Aug 17, 2022)
16-89268493-T-A		KBG syndrome	Likely benign (May 31, 2023)
16-89268513-C-T		KBG syndrome	Uncertain significance (Apr 20, 2022)
16-89268514-G-A		KBG syndrome	Likely benign (Apr 19, 2022)
16-89268517-C-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
16-89268518-A-G		KBG syndrome	Uncertain significance (Jul 01, 2022)
16-89268525-C-T			Likely pathogenic (Sep 06, 2022)
16-89268526-G-A		Inborn genetic diseases • KBG syndrome	Likely benign (Sep 01, 2022)
16-89268526-G-T		KBG syndrome	Likely pathogenic (Jun 16, 2016)
16-89268527-TAGA-T			Uncertain significance (Oct 27, 2022)
16-89268531-A-AGG		not specified	Uncertain significance (Mar 16, 2022)
16-89268538-C-A		KBG syndrome	Likely benign (May 08, 2022)
16-89268541-C-G		Inborn genetic diseases • KBG syndrome	Uncertain significance (Feb 16, 2023)
16-89268543-C-T			Uncertain significance (May 17, 2018)
16-89268544-G-A		KBG syndrome	Likely benign (Dec 18, 2023)
16-89268549-C-T			Uncertain significance (Jan 11, 2022)
16-89268581-T-TCCTGCACCTTCAGCTGCCACTC			Uncertain significance (Apr 30, 2019)
16-89268583-C-T		Inborn genetic diseases • KBG syndrome	Likely benign (Dec 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANKRD11	protein_coding	protein_coding	ENST00000301030	11	222932

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.69e-11	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.554	1657	1.59e+3	1.04	0.000114	17483
Missense in Polyphen		463	660.5	0.70098		7316
Synonymous	-7.96	1033	755	1.37	0.0000660	5171
Loss of Function	8.17	4	85.5	0.0468	0.00000496	1133

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000977	0.0000924
European (Non-Finnish)	0.0000374	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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:25556659}.
• Disease: DISEASE: KBG syndrome (KBGS) [MIM:148050]: A syndrome characterized by macrodontia of the upper central incisors, distinctive craniofacial findings, short stature, skeletal anomalies, and neurologic involvement that includes global developmental delay, seizures, and intellectual disability. {ECO:0000269|PubMed:21782149, ECO:0000269|PubMed:25413698}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.0131
• rvis_EVS: -4.38
• rvis_percentile_EVS: 0.09

Haploinsufficiency Scores

• pHI: 0.249
• hipred: Y
• hipred_score: 0.689
• ghis: 0.633

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.934

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ankrd11
• Phenotype: hematopoietic system phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype

Gene ontology

• Biological process: in utero embryonic development;tissue homeostasis;multicellular organism growth;odontogenesis of dentin-containing tooth;skeletal system morphogenesis;face morphogenesis;bone development
• Cellular component: nucleus;nucleoplasm;cytosol;plasma membrane