ANKRD11

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

Basic information

Region (hg38): 16:89267619-89490561

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
• congenital heart defects, multiple types (Limited), mode of inheritance: AD
• KBG syndrome (Definitive), mode of inheritance: AD
• KBG syndrome (Definitive), mode of inheritance: AD
• KBG syndrome (Strong), mode of inheritance: AD
• KBG syndrome (Supportive), 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 (2139 variants)
• not_provided (1126 variants)
• Inborn_genetic_diseases (836 variants)
• ANKRD11-related_disorder (211 variants)
• not_specified (137 variants)
• Intellectual_disability (39 variants)
• Global_developmental_delay (19 variants)
• See_cases (9 variants)
• Rare_genetic_intellectual_disability (6 variants)
• Neurodevelopmental_disorder (6 variants)
• Encephalopathy,_progressive,_early-onset,_with_episodic_rhabdomyolysis (5 variants)
• Seizure (3 variants)
• Developmental_disorder (3 variants)
• Autism_spectrum_disorder (2 variants)
• Abnormality_of_the_nervous_system (2 variants)
• Retrognathia (1 variants)
• Esotropia (1 variants)
• Epilepsy (1 variants)
• Delayed_speech_and_language_development (1 variants)
• Epicanthus (1 variants)
• Chromatinopathy (1 variants)
• Conductive_hearing_impairment (1 variants)
• Short_foot (1 variants)
• Short_palm (1 variants)
• Clinodactyly_of_the_5th_finger (1 variants)
• Neurodevelopmental_abnormality (1 variants)
• Sudden_unexplained_death_in_childhood (1 variants)
• Atypical_behavior (1 variants)
• Hypertelorism (1 variants)
• Multiple_congenital_anomalies/dysmorphic_syndrome (1 variants)
• Obesity (1 variants)
• Hand_tremor (1 variants)
• Dystonia,_early-onset,_and/or_spastic_paraplegia (1 variants)
• Decreased_total_neutrophil_count (1 variants)
• Wide_nasal_bridge (1 variants)
• Ptosis (1 variants)
• Cryptorchidism (1 variants)
• Neurodevelopmental_delay (1 variants)
• Hypermetropia (1 variants)
• Vascular_disorder (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Unilateral_cryptorchidism (1 variants)
• Moderate_intellectual_deficiency (1 variants)
• Monogenic_short_statue (1 variants)
• Abnormal_facial_shape (1 variants)
• Macrocephaly (1 variants)
• Astigmatism (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. These statistics are base on transcript: NM_000013275.6. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	684	34	728
missense	14	40	1194	353	32	1633
nonsense	138	49	3			190
start loss						0
frameshift	297	109	4			410
splice donor/acceptor (+/-2bp)	14	10	3			27
Total	463	208	1214	1037	66

Highest pathogenic variant AF is 0.000012392787

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
		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

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

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