ANKRD11

Chr 16AD

ankyrin repeat domain 11

Also known as: ANCO-1, ANCO1, LZ16, T13

NCBI Gene: 29123ENSG00000167522UniProt: Q6UB99

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. [provided by RefSeq, Jan 2012]

Primary Disease Associations & Inheritance

KBG syndromeMIM #148050
AD
600
ClinVar variants
86
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— ANKRD11
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Gene-Disease Validity (ClinGen)
KBG syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
86 Pathogenic / Likely Pathogenic· 315 VUS of 600 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.11LOEUF
pLI 1.000
Z-score 8.17
OE 0.05 (0.02–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.55Z-score
OE missense 1.04 (1.00–1.08)
1657 obs / 1594.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (1.00–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.37
0≤1.21.6
LoF obs/exp: 4 / 85.5Missense obs/exp: 1657 / 1594.8Syn Z: -7.96

ClinVar Variant Classifications

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic26
VUS315
Likely Benign166
Benign18
Conflicting15
60
Pathogenic
26
Likely Pathogenic
315
VUS
166
Likely Benign
18
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
39
1
20
0
60
Likely Pathogenic
16
1
9
0
26
VUS
0
291
21
3
315
Likely Benign
0
19
24
123
166
Benign
0
8
1
9
18
Conflicting
—15
Total5532075135600

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ANKRD11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ANKRD11-related KBG syndrome

definitive
ADUndeterminedDecreased Gene Product Level
Dev. Disorders
G2P ↗
frameshift variantstop gained5 prime UTR variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

KBG syndrome

MIM #148050

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — ANKRD11
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ANKRD11 variants: KBG syndrome and beyond.
Parenti I et al.·Clin Genet
2021
Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.
Kaur M et al.·Am J Med Genet A
2023Functional
Clinical description, molecular delineation and genotype-phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients.
Martinez-Cayuelas E et al.·J Med Genet
2023Cohort
Insights into the ANKRD11 variants and short-stature phenotype through literature review and ClinVar database search.
He D et al.·Orphanet J Rare Dis
2024Review
The expanding phenotypes of cohesinopathies: one ring to rule them all!
Piché J et al.·Cell Cycle
2019Review
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
KBG syndrome.
Morel Swols D et al.·Orphanet J Rare Dis
2017Review
Cornelia de Lange Spectrum.
Ascaso Á et al.·An Pediatr (Engl Ed)
2024
Deletion of first noncoding exon in ANKRD11 leads to KBG syndrome.
Borja N et al.·Am J Med Genet A
2023Review
ANKRD11 binding to cohesin suggests a connection between KBG syndrome and Cornelia de Lange syndrome.
Liu H et al.·Proc Natl Acad Sci U S A
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Functional Data Strengthen Clinical Validation of PhenoScore Phenotype-Guided AI for ANKRD11 Missense Variants.
Andriessen E et al.·Clin Genet
2026Functional
A novel heterozygous mutation of ANKRD11 causes KBG syndrome in a preterm neonate: a case report and literature review.
Gao J et al.·Front Pediatr
2025🔓 Open AccessReview
KBG syndrome-associated protein ANKRD11 regulates SETD5 expression to modulate rRNA levels and translation.
Sashiyama S et al.·iScience
2025🔓 Open Access
ANKRD11 as a potential biomarker for brain metastasis from lung adenocarcinoma via cerebrospinal fluid liquid biopsy.
Sun Q et al.·Transl Lung Cancer Res
2025🔓 Open Access
16q24.3 Microdeletions Disrupting Upstream Non-Coding Region of ANKRD11 Cause KBG Syndrome.
Iwata-Otsubo A et al.·Genes (Basel)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools