ANKRD11

Summary

ANKRD11 (ankyrin repeat domain 11, HGNC:21316) is a protein-coding gene on chromosome 16q24.3, encoding Ankyrin repeat domain-containing protein 11 (Q6UB99). Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells. It is a selective cancer dependency (DepMap: 22.7% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X.

Source: NCBI Gene 29123 — RefSeq curated summary.

At a glance

• Gene–disease (curated): KBG syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 3,439 total — 485 pathogenic, 170 likely-pathogenic
• Phenotypes (HPO): 102
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 22.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_013275

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21316
Approved symbol	ANKRD11
Name	ankyrin repeat domain 11
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	LZ16, T13, ANCO1, ANCO-1
Ensembl gene	ENSG00000167522
Ensembl biotype	protein_coding
OMIM	611192
Entrez	29123

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 18 protein_coding, 9 protein_coding_CDS_not_defined, 8 retained_intron, 6 nonsense_mediated_decay

ENST00000301030, ENST00000330736, ENST00000378330, ENST00000378332, ENST00000562194, ENST00000562211, ENST00000562275, ENST00000562816, ENST00000563291, ENST00000564553, ENST00000566858, ENST00000566973, ENST00000567699, ENST00000567736, ENST00000568100, ENST00000568512, ENST00000568924, ENST00000623388, ENST00000642333, ENST00000642443, ENST00000642600, ENST00000642695, ENST00000643147, ENST00000643964, ENST00000644045, ENST00000644139, ENST00000644285, ENST00000644784, ENST00000645212, ENST00000645278, ENST00000645664, ENST00000645666, ENST00000645844, ENST00000646166, ENST00000646345, ENST00000646413, ENST00000646838, ENST00000646975, ENST00000647213, ENST00000647238, ENST00000647539

RefSeq mRNA: 3 — MANE Select: NM_013275 NM_001256182, NM_001256183, NM_013275

CCDS: CCDS32513

Canonical transcript exons

ENST00000301030 — 13 exons

Exon	Start	End
ENSE00001229505	89418284	89418368
ENSE00001229512	89490245	89490561
ENSE00002230566	89267630	89268663
ENSE00003474344	89279072	89285649
ENSE00003497469	89274814	89274957
ENSE00003504243	89290625	89290828
ENSE00003537320	89316933	89317078
ENSE00003555072	89291013	89291183
ENSE00003624279	89288528	89288670
ENSE00003637408	89275093	89275191
ENSE00003663446	89305206	89305344
ENSE00003674059	89286039	89286186
ENSE00003693211	89270817	89270909

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.4584 / max 1519.6763, expressed in 1827 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158633	51.9190	1827
158622	1.6509	737
158620	1.6153	685
158621	0.8924	388
158624	0.7874	287
158634	0.6896	376
158618	0.4479	203
158623	0.3849	120
158619	0.0711	32

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.61	gold quality
sural nerve	UBERON:0015488	98.28	gold quality
stromal cell of endometrium	CL:0002255	96.64	gold quality
adenohypophysis	UBERON:0002196	96.16	gold quality
colonic epithelium	UBERON:0000397	95.86	gold quality
left ovary	UBERON:0002119	95.67	gold quality
lower esophagus mucosa	UBERON:0035834	95.52	gold quality
pituitary gland	UBERON:0000007	95.45	gold quality
right ovary	UBERON:0002118	95.27	gold quality
skin of abdomen	UBERON:0001416	95.18	gold quality
upper lobe of left lung	UBERON:0008952	95.11	gold quality
right lung	UBERON:0002167	95.07	gold quality
ventricular zone	UBERON:0003053	95.07	gold quality
granulocyte	CL:0000094	95.05	gold quality
ectocervix	UBERON:0012249	94.96	gold quality
skin of leg	UBERON:0001511	94.95	gold quality
body of uterus	UBERON:0009853	94.93	gold quality
medial globus pallidus	UBERON:0002477	94.92	gold quality
right frontal lobe	UBERON:0002810	94.91	gold quality
mucosa of stomach	UBERON:0001199	94.89	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.88	gold quality
lower esophagus	UBERON:0013473	94.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.78	gold quality
left uterine tube	UBERON:0001303	94.72	gold quality
metanephros cortex	UBERON:0010533	94.71	gold quality
right atrium auricular region	UBERON:0006631	94.52	gold quality
upper lobe of lung	UBERON:0008948	94.50	gold quality
left adrenal gland cortex	UBERON:0035825	94.47	gold quality
apex of heart	UBERON:0002098	94.43	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	13.51
E-CURD-46	yes	8.12
E-MTAB-3929	no	343.61
E-MTAB-6524	no	166.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BDNF	Activation
CORO1B	Activation
GAP43	Activation
NTRK2	Activation
RAB13	Activation

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

42 targeting ANKRD11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 22.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 38)

• Together, these results indicate that the transcriptional potential of ANCO-1 may be modulated by a combination of repression and activation signals. (PMID:17521611)
• ANKRD11 has a role as a p53 coactivator and may be involved in a regulatory feedback loop with p53 (PMID:18840648)
• ANKRD11 is a candidate gene for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome. (PMID:19920853)
• Mutations in ANKRD11 cause KBG syndrome and outline a fundamental role of ANKRD11 in craniofacial, dental, skeletal, and central nervous system development and function. (PMID:21782149)
• aberrant DNA methylation of three CpGs in a 19 bp region within the ANKRD11 promoter may be responsible for its down-regulation in breast cancer. (PMID:22538187)
• The complete neurological and psychiatric features observed in two patients with KBG syndrome due to ANKRD11 mutations, are reported. (PMID:23184435)
• Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome. (PMID:23494856)
• AIB1, AIB1-delta4 and ANCO1 are important determinants of endocrine and growth factor responsiveness in breast cancer. (PMID:24678732)
• ANKRD11 C-terminus plays an important role in regulating the abundance of the protein, and a disturbance of the protein abundance due to the mutations leads to KBG syndrome. (PMID:25413698)
• Further delineation of the KBG syndrome phenotype on large patients cohort caused by ANKRD11 aberrations has been presented. (PMID:25424714)
• we conclude that severe short stature, intellectual disability, and macrodontia are the main characteristics in KBG syndrome related to ANKRD11 mutation (PMID:25464108)
• These findings point out the importance of screening ANKRD11 in young CdLS patients who were found to be negative for mutations in the five known CdLS genes. (PMID:25652421)
• Here we report a large series of 39 patients with KBG syndrome; these patients harbored ANKRD11 mutations (20 cases) or deletions (19 cases). All the mutations were found by targeted molecular analysis on patients with clinical features suggestive of KBG. (PMID:27605097)
• exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the molecular diagnosis of KBG syndrome. (PMID:27900361)
• ANKRD11 variants cause variable clinical features associated with KBG syndrome and Coffin-Siris-like syndrome. (PMID:28250421)
• Twelve novel cases of haploinsufficiency for ANKRD11-flanking genes make the difference between KBG and 16q24.3 microdeletion syndromes. (PMID:28422132)
• ANKRD11 variants cause KBG syndrome and Coffin-Siris-like syndrome. (PMID:28566769)
• Novel ANKRD11 gene mutation in an individual with a mild phenotype of KBG syndrome associated to a GEFS+ phenotypic spectrum. (PMID:30642272)
• Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression. (PMID:31788936)
• KBG syndrome: Common and uncommon clinical features based on 31 new patients. (PMID:32124548)
• KBG syndrome in two patients from Egypt. (PMID:32222090)
• Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome. (PMID:32476269)
• [Analysis of ANKRD11 gene variant in a family affected with KBG syndrome]. (PMID:32820523)
• Two loss-of-function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway. (PMID:33354850)
• ANKRD11 variants: KBG syndrome and beyond. (PMID:33955014)
• [Gender difference in clinical manifestations of KBG syndrome due to variants of ANKRD11 gene]. (PMID:34247373)
• Wide Fontanels, Delayed Speech Development and Hoarse Voice as Useful Signs in the Diagnosis of KBG Syndrome: A Clinical Description of 23 Cases with Pathogenic Variants Involving the ANKRD11 Gene or Submicroscopic Chromosomal Rearrangements of 16q24.3. (PMID:34440431)
• Abnormal frontal gyrification pattern and uncinate development in patients with KBG syndrome caused by ANKRD11 aberrations. (PMID:34547584)
• Clinical and genetic characteristics of Keishi-Bukuryo-Gan syndrome: an analysis of 5 cases. (PMID:34704418)
• [Analysis of three patients with KBG syndrome and epileptic seizures due to variants of ANKRD11 gene]. (PMID:35598261)
• Expanding the Molecular Spectrum of ANKRD11 Gene Defects in 33 Patients with a Clinical Presentation of KBG Syndrome. (PMID:35682590)
• Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein. (PMID:35833929)
• ANKRD11 pathogenic variants and 16q24.3 microdeletions share an altered DNA methylation signature in patients with KBG syndrome. (PMID:36440975)
• [Clinical and genetic analysis of three children with KBG syndrome due to novel variants of ANKRD11 gene]. (PMID:36584991)
• Deletion of first noncoding exon in ANKRD11 leads to KBG syndrome. (PMID:36628575)
• Identification and functional characterization of a bipartite nuclear localization signal in ANKRD11. (PMID:37290286)
• Loss of ANCO1 Expression Regulates Chromatin Accessibility and Drives Progression of Early-Stage Triple-Negative Breast Cancer. (PMID:37511268)
• Insights into the ANKRD11 variants and short-stature phenotype through literature review and ClinVar database search. (PMID:39135054)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd11	ENSDARG00000051886
mus_musculus	Ankrd11	ENSMUSG00000035569
rattus_norvegicus	Ankrd11	ENSRNOG00000027906

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 11 — Q6UB99 (reviewed: Q6UB99)

Alternative names: Ankyrin repeat-containing cofactor 1

All UniProt accessions (13): A0A2R8Y438, A0A2R8Y4T9, A0A2R8Y5V1, A0A2R8Y728, A0A2R8Y7Z1, A0A2R8YE03, A0A2R8YE94, A0A2R8YEI0, H0Y2U4, H0Y3E3, H3BNU4, Q6UB99, X5D778

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells. May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation. Has a role in proliferation and development of cortical neural precursors. May also regulate bone homeostasis.

Subunit / interactions. Interacts with the PAS region of the p160 coactivators.

Subcellular location. Nucleus.

Post-translational modifications. Subject to proteasomal degradation which is probably essential to regulate its activity.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (3): NP_001243111, NP_001243112, NP_037407* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR042636	ANKRD11	Family

Pfam: PF12796

UniProt features (70 total): compositionally biased region 32, modified residue 18, region of interest 12, repeat 4, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UB99-F1	39.44	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (18): 276, 408, 410, 411, 834, 1079, 1120, 1123, 1419, 1509, 1692, 1792, 1847, 1850, 1851, 1852, 1859, 1990

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 450 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_BODY_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, AATGGAG_MIR136, CEBPB_01, FOXD3_01, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GGGCATT_MIR365, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, RHEIN_ALL_GLUCOCORTICOID_THERAPY_UP, MODULE_206

GO Biological Process (5): odontogenesis of dentin-containing tooth (GO:0042475), skeletal system morphogenesis (GO:0048705), face morphogenesis (GO:0060325), head morphogenesis (GO:0060323), face development (GO:0060324)

GO Molecular Function (2): protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure morphogenesis	2
head development	2
cellular anatomical structure	2
odontogenesis	1
skeletal system development	1
animal organ morphogenesis	1
head morphogenesis	1
face development	1
body morphogenesis	1
anatomical structure development	1
binding	1
protein binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

2119 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD11	TP53	P04637	671
ANKRD11	ZNF778	Q96MU6	622
ANKRD11	NIPBL	Q6KC79	594
ANKRD11	SMC1A	Q14683	580
ANKRD11	SETD5	Q9C0A6	578
ANKRD11	SMC3	Q9UQE7	541
ANKRD11	NCOA3	Q9Y6Q9	536
ANKRD11	MED13L	Q71F56	532
ANKRD11	NCOA2	Q15596	526
ANKRD11	HDAC5	Q9UQL6	521
ANKRD11	ARID1B	Q8NFD5	506
ANKRD11	NR3C2	P08235	499
ANKRD11	DLGAP2	Q9P1A6	491
ANKRD11	AFF4	Q9UHB7	487
ANKRD11	RAD21	O60216	481

IntAct

39 interactions, top by confidence:

A	B	Type	Score
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
HDAC3	KDM1A	psi-mi:“MI:0914”(association)	0.650
GPS2	DCTN6	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
ANKRD11	IQGAP1	psi-mi:“MI:0915”(physical association)	0.400
ANKRD11	CFAP418	psi-mi:“MI:0915”(physical association)	0.370
RACGAP1	STX18	psi-mi:“MI:0914”(association)	0.350
Cdc26	PEX10	psi-mi:“MI:0914”(association)	0.350
Rbm8a	GOSR1	psi-mi:“MI:0914”(association)	0.350
Wdr5	MGA	psi-mi:“MI:0914”(association)	0.350
Setd5	NCOR2	psi-mi:“MI:0914”(association)	0.350
Cbx4	DNAJB6	psi-mi:“MI:0914”(association)	0.350
ARRB2	ANKRD11	psi-mi:“MI:0914”(association)	0.350
SYNCRIP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CSNK2A1	EIF3F	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CSNK2B	OSBPL8	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
PEA15	CLASP2	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
SMC5	DKFZp686H10254	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PPIL4	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ZNF800	MED19	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (226): ANKRD11 (Affinity Capture-MS), NCOA1 (Reconstituted Complex), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-MS), ANKRD11 (Synthetic Lethality), ANKRD11 (Affinity Capture-MS), ANKRD11 (Affinity Capture-RNA), ANKRD11 (Affinity Capture-RNA), ANKRD11 (Affinity Capture-MS)

ESM2 similar proteins: A2A6A1, B0BN49, B0QZF7, D2H526, E1BB50, E9PYH6, E9Q4F7, E9Q6J5, F1Q8W0, O15047, O88453, P30414, P30415, Q01538, Q14AX6, Q17QQ9, Q27450, Q3KPW4, Q3UMU9, Q4V8I5, Q505I5, Q5BKY9, Q5SW79, Q5VZP5, Q62417, Q66648, Q66PJ3, Q6A065, Q6P9P0, Q6UB99, Q7TQC7, Q7Z4V5, Q80U49, Q86VM9, Q8BYK8, Q8C5W0, Q8CFC2, Q8NEY8, Q8R0F5, Q8R2M2

Diamond homologs: E9Q4F7, Q6UB98, Q6UB99

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
ANKRD11	“up-regulates activity”	TP53	binding
TP53	“up-regulates quantity by expression”	ANKRD11	“transcriptional regulation”
ANKRD11	up-regulates	Dendritic_spine_morphogenesis
ANKRD11	“up-regulates quantity by expression”	NTRK2	“transcriptional regulation”
ANKRD11	“up-regulates quantity by expression”	BDNF	“transcriptional regulation”
ANKRD11	up-regulates	Neurite_outgrowth
ANKRD11	“up-regulates quantity by expression”	GAP43	“transcriptional regulation”
ANKRD11	“up-regulates quantity by expression”	CORO1B	“transcriptional regulation”
ANKRD11	“up-regulates quantity by expression”	RAB13	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MLYM.

Clinical variants and AI predictions

ClinVar

3439 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	485
Likely pathogenic	170
Uncertain significance	1388
Likely benign	875
Benign	126

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012411	NM_013275.6(ANKRD11):c.3768_3769del (p.His1256fs)	Pathogenic
1027800	NM_013275.6(ANKRD11):c.3651C>A (p.Tyr1217Ter)	Pathogenic
1029215	NM_013275.6(ANKRD11):c.5145C>G (p.Tyr1715Ter)	Pathogenic
1031765	NM_013275.6(ANKRD11):c.2793dup (p.Gly932fs)	Pathogenic
1031769	NM_013275.6(ANKRD11):c.5550C>G (p.Tyr1850Ter)	Pathogenic
1031770	NM_013275.6(ANKRD11):c.5651C>G (p.Ser1884Ter)	Pathogenic
1031774	NM_013275.6(ANKRD11):c.7519C>T (p.Gln2507Ter)	Pathogenic
1064442	NM_013275.6(ANKRD11):c.5117del (p.Pro1706fs)	Pathogenic
1065425	NM_013275.6(ANKRD11):c.3843dup (p.Glu1282Ter)	Pathogenic
1065426	NM_013275.6(ANKRD11):c.4396_4397del (p.Arg1466fs)	Pathogenic
1068793	NM_013275.6(ANKRD11):c.5117dup (p.Thr1707fs)	Pathogenic
1073378	NM_013275.6(ANKRD11):c.7062dup (p.Ser2355fs)	Pathogenic
1098344	NM_013275.6(ANKRD11):c.602-1G>A	Pathogenic
1098347	NM_013275.6(ANKRD11):c.1523del (p.Val508fs)	Pathogenic
1164005	NM_013275.6(ANKRD11):c.5647_5651del (p.Phe1883fs)	Pathogenic
1172606	NM_013275.6(ANKRD11):c.5494_5495del (p.Arg1832fs)	Pathogenic
1184001	NM_013275.6(ANKRD11):c.2553_2556del (p.Asp851fs)	Pathogenic
1184461	NM_013275.6(ANKRD11):c.3127del (p.Leu1043fs)	Pathogenic
1184462	NM_013275.6(ANKRD11):c.980_993del (p.Leu327fs)	Pathogenic
1190014	NM_013275.6(ANKRD11):c.5334_5344del (p.Pro1779fs)	Pathogenic
1197090	NM_013275.6(ANKRD11):c.4624_4625del (p.Lys1542fs)	Pathogenic
1210092	NM_013275.6(ANKRD11):c.7806+1G>T	Pathogenic
1212718	NM_013275.6(ANKRD11):c.2054_2055del (p.Lys685fs)	Pathogenic
1215859	NM_013275.6(ANKRD11):c.7192C>T (p.Gln2398Ter)	Pathogenic
1251930	NM_013275.6(ANKRD11):c.4055_4058del (p.His1352fs)	Pathogenic
1299327	NM_013275.6(ANKRD11):c.1742_1743del (p.Ser580_Ser581insTer)	Pathogenic
1320081	NM_013275.6(ANKRD11):c.397+1G>A	Pathogenic
1320207	NM_013275.6(ANKRD11):c.226+1G>A	Pathogenic
1321993	NM_013275.6(ANKRD11):c.6923del (p.Gly2308fs)	Pathogenic
1323154	NM_013275.6(ANKRD11):c.2288_2289del (p.Glu763fs)	Pathogenic

SpliceAI

5949 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89268659:CAAGT:C	acceptor_gain	1.0000
16:89270814:GAC:G	donor_loss	1.0000
16:89270815:ACC:A	donor_loss	1.0000
16:89270831:A:AC	donor_gain	1.0000
16:89270832:C:CC	donor_gain	1.0000
16:89270845:T:TA	donor_gain	1.0000
16:89270905:TCACC:T	acceptor_gain	1.0000
16:89270906:CACC:C	acceptor_gain	1.0000
16:89270906:CACCC:C	acceptor_gain	1.0000
16:89270907:ACC:A	acceptor_gain	1.0000
16:89270907:ACCC:A	acceptor_loss	1.0000
16:89270908:CC:C	acceptor_gain	1.0000
16:89270908:CCC:C	acceptor_gain	1.0000
16:89270909:CCTG:C	acceptor_gain	1.0000
16:89270910:C:CC	acceptor_gain	1.0000
16:89270911:T:G	acceptor_loss	1.0000
16:89270912:G:C	acceptor_gain	1.0000
16:89270912:G:GC	acceptor_gain	1.0000
16:89270920:C:CT	acceptor_gain	1.0000
16:89270920:C:T	acceptor_gain	1.0000
16:89273242:T:TA	donor_gain	1.0000
16:89274808:CCCTA:C	donor_loss	1.0000
16:89274809:CCTA:C	donor_loss	1.0000
16:89274810:CTA:C	donor_loss	1.0000
16:89274811:TA:T	donor_loss	1.0000
16:89274813:CCTGG:C	donor_gain	1.0000
16:89274953:TTCTC:T	acceptor_gain	1.0000
16:89274955:CTC:C	acceptor_gain	1.0000
16:89274956:TC:T	acceptor_gain	1.0000
16:89274957:CC:C	acceptor_gain	1.0000

AlphaMissense

17620 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:89268593:A:G	L2626P	1.000
16:89268600:A:G	W2624R	1.000
16:89268600:A:T	W2624R	1.000
16:89270851:A:G	L2591P	1.000
16:89270855:A:G	W2590R	1.000
16:89270855:A:T	W2590R	1.000
16:89270862:G:C	F2587L	1.000
16:89270862:G:T	F2587L	1.000
16:89270863:A:G	F2587S	1.000
16:89270864:A:G	F2587L	1.000
16:89270878:A:G	F2582S	1.000
16:89274848:T:A	D2560V	1.000
16:89274851:A:G	L2559P	1.000
16:89274854:A:G	L2558P	1.000
16:89274862:G:C	C2555W	1.000
16:89274864:A:G	C2555R	1.000
16:89274871:G:C	F2552L	1.000
16:89274871:G:T	F2552L	1.000
16:89274873:A:G	F2552L	1.000
16:89274902:G:T	A2542D	1.000
16:89274923:A:G	L2535P	1.000
16:89274950:A:G	L2526P	1.000
16:89275118:A:G	L2515P	1.000
16:89279217:A:G	L2442P	1.000
16:89279298:A:G	L2415P	1.000
16:89285495:A:C	F349L	1.000
16:89285495:A:T	F349L	1.000
16:89285497:A:G	F349L	1.000
16:89286083:A:G	L283P	1.000
16:89286083:A:T	L283Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000001336 (16:89298371 G>A), RS1000003252 (16:89276351 A>G), RS1000021191 (16:89467386 G>A), RS1000027211 (16:89357328 C>A), RS1000030815 (16:89464331 G>A), RS1000036206 (16:89477699 G>A), RS1000048969 (16:89359251 C>T), RS1000057912 (16:89279897 C>G,T), RS1000061492 (16:89443762 G>C), RS1000074429 (16:89339096 G>A), RS1000088537 (16:89353008 C>T), RS1000112681 (16:89368375 T>G), RS1000120244 (16:89413487 T>C), RS1000121217 (16:89491514 A>G), RS1000122484 (16:89401357 C>A,G,T)

Disease associations

OMIM: gene MIM:611192 | disease phenotypes: MIM:148050, MIM:618331, MIM:227650, MIM:219050, MIM:603047, MIM:607259, MIM:619681

GenCC curated gene-disease

Disease	Classification	Inheritance
KBG syndrome	Definitive	Autosomal dominant
congenital heart defects, multiple types	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
KBG syndrome	Definitive	AD

Mondo (22): KBG syndrome (MONDO:0007846), intellectual disability (MONDO:0001071), congenital nervous system disorder (MONDO:0002320), neutropenia (MONDO:0001475), neurodevelopmental disorder (MONDO:0700092), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), encephalopathy, progressive, early-onset, with episodic rhabdomyolysis (MONDO:0032681), Fanconi anemia (MONDO:0019391), hyperopia (MONDO:0004891), esotropia (MONDO:0004896), cryptorchidism (MONDO:0009047), astigmatism (MONDO:0011284), autism spectrum disorder (MONDO:0005258), ptosis (MONDO:0000728), conductive hearing loss disorder (MONDO:0020679)

Orphanet (9): KBG syndrome (Orphanet:2332), Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341), Rare genetic intellectual disability (Orphanet:183757), Fanconi anemia (Orphanet:84), Spastic paraplegia type 7 (Orphanet:99013), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

102 total (30 of 102 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000039	Epispadias
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000294	Low anterior hairline
HP:0000307	Pointed chin
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000384	Preauricular skin tag
HP:0000389	Chronic otitis media
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004627_163	Lymphocyte count	1.000000e-10
GCST010083_105	Hemoglobin levels	6.000000e-10
GCST012226_392	Waist circumference adjusted for body mass index	2.000000e-08
GCST012490_23	Femur bone mineral density x serum urate levels interaction	1.000000e-12
GCST012490_583	Femur bone mineral density x serum urate levels interaction	7.000000e-11
GCST90002381_102	Eosinophil count	4.000000e-09
GCST90002388_477	Lymphocyte count	2.000000e-09
GCST90020028_1504	Hip circumference adjusted for BMI	7.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0004509	hemoglobin measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004531	urate measurement
EFO:0004842	eosinophil count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D001251	Astigmatism	C11.744.212
D001763	Blepharoptosis	C11.338.204
D003456	Cryptorchidism	C12.100.500.829.258; C12.200.294.829.258; C12.200.706.258; C12.800.258; C16.131.939.258; C19.391.829.258
D004827	Epilepsy	C10.228.140.490
D004948	Esotropia	C10.292.562.887.300; C11.590.810.400
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
D006956	Hyperopia	C11.744.479
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
D014652	Vascular Diseases	C14.907
C537015	KBG syndrome (supp.)
C564599	Spastic Paraplegia 7, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

73 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression, affects expression, affects cotreatment, increases methylation (+1 more)	5
sodium arsenite	affects methylation, affects cotreatment, decreases expression, increases abundance, increases expression	4
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
Air Pollutants	affects cotreatment, affects expression, affects oxidation, increases abundance	3
Tobacco Smoke Pollution	decreases expression, increases expression, increases methylation	3
Cyclosporine	increases expression	3
bisphenol S	affects cotreatment, increases methylation, decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression, affects methylation	2
Cisplatin	decreases expression	2
Fluorouracil	affects expression, increases expression	2
Ozone	increases abundance, affects cotreatment, affects expression, affects oxidation	2
Valproic Acid	increases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, affects expression, affects oxidation, increases abundance	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	decreases expression, increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, affects expression, affects oxidation, increases abundance	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1QE	HAP1 ANKRD11 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

200 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06465641	PHASE4	RECRUITING	Methylphenidate in KBG Syndrome: N-of-1 Series
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)