ANKRD11

Chr 16AD

ankyrin repeat domain 11

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

NCBI Gene: 29123ENSG00000167522UniProt: Q6UB99OMIM: 611192

The protein functions as a transcriptional repressor that inhibits ligand-dependent activation of transcription. Mutations cause KBG syndrome, an autosomal dominant disorder characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures, and intellectual disability. Disease predominantly occurs through loss-of-function, consistent with the gene's extreme intolerance to such variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.111 OMIM phenotype
Clinical Summary— ANKRD11
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Gene-Disease Validity (ClinGen)
KBG syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.
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ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 218 VUS of 400 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
-0.55Z-score
OE missense 1.04 (1.00–1.08)
1657 obs / 1594.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.05 (0.02–0.11)
0≤0.351.4
Missense OE1.04 (1.00–1.08)
0≤0.61.4
Synonymous OE1.37
0≤1.21.6
LoF obs/exp: 4 / 85.5Missense obs/exp: 1657 / 1594.8Syn Z: -7.96
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveANKRD11-related KBG syndromeOTHERAD
DN
0.2599th %ile
GOF
0.1699th %ile
LOF
0.89top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 96% of P/LP variants are LoF · LOEUF 0.11

Literature Evidence

LOFKBG syndrome, caused by ANKRD11 gene haploinsufficiency, is a chromatin related syndrome not formally belonging to this category.PMID:32793091

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic12
VUS218
Likely Benign117
Benign15
Conflicting5
33
Pathogenic
12
Likely Pathogenic
218
VUS
117
Likely Benign
15
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
32
0
1
0
33
Likely Pathogenic
11
1
0
0
12
VUS
1
209
7
1
218
Likely Benign
0
10
15
92
117
Benign
0
8
3
4
15
Conflicting
—5
Total442282697400

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search 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
Novel ANKRD11 Mutation in KBG Syndrome: A diagnostic triad of hearing loss, radiological macrodontia and artificial intelligence-assisted facial phenotyping.
Laaraje A et al.·Sultan Qaboos Univ Med J
2026Open Access
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
2025Open AccessReview
KBG syndrome-associated protein ANKRD11 regulates SETD5 expression to modulate rRNA levels and translation.
Sashiyama S et al.·iScience
2025Open 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
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients