TANC2

Chr 17AD

tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2

NCBI Gene: 26115ENSG00000170921UniProt: Q9HCD6

Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines

Primary Disease Associations & Inheritance

Intellectual developmental disorder with autistic features and language delay, with or without seizuresMIM #618906
AD
495
ClinVar variants
55
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— TANC2
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Gene-Disease Validity (ClinGen)
intellectual developmental disorder with autistic features and language delay, with or without seizures · 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
55 Pathogenic / Likely Pathogenic· 376 VUS of 495 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.
0.16LOEUF
pLI 1.000
Z-score 8.09
OE 0.09 (0.05–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.34Z-score
OE missense 0.80 (0.76–0.85)
900 obs / 1120.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.09 (0.05–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.76–0.85)
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.0.95
0≤1.21.6
LoF obs/exp: 8 / 91.5Missense obs/exp: 900 / 1120.8Syn Z: 0.86

ClinVar Variant Classifications

495 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic27
VUS376
Likely Benign52
Benign7
Conflicting5
28
Pathogenic
27
Likely Pathogenic
376
VUS
52
Likely Benign
7
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
19
0
28
Likely Pathogenic
16
0
11
0
27
VUS
7
343
22
4
376
Likely Benign
0
30
3
19
52
Benign
0
1
1
5
7
Conflicting
—5
Total323745628495

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

View in ClinVar →

Protein Context — Lollipop Plot

TANC2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TANC2-related neurodevelopmental and psychiatric disorders

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder with autistic features and language delay, with or without seizures

MIM #618906

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.
Guo H et al.·Nat Commun
2019
[Clinical and genetic analysis of two children with TANC2 gene variants and a literature review].
Chu M et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2024Review
De novo TANC2 variants caused developmental and epileptic encephalopathy and epilepsy.
Luo S et al.·Epilepsia
2025
Variants in CALD1, ESRP1, and RBFOX1 are associated with orofacial cleft risk.
Carlson JC et al.·PLoS Genet
2025Meta-analysis
Truncating mutation in TANC2 in a Chinese boy associated with Lennox-Gastaut syndrome: a case report.
Tian Y et al.·BMC Pediatr
2021Case report
17q23.3 de novo microdeletion involving only TANC2 gene: A new case.
Tassano E et al.·Eur J Med Genet
2020Case report
Prediction of Lymph Node Metastasis in Non-Small Cell Lung Carcinoma Using Primary Tumor Somatic Mutation Data.
Lee V et al.·JCO Clin Cancer Inform
2025
Investigating the Role of Gene Polymorphisms in Hypertension: Evidence from the Jordanian Population.
Al-Sanabra O et al.·Vasc Health Risk Manag
2025
Genetic testing after sudden death with negative ancillary investigations: A French prospective study with multidisciplinary collaboration.
Osouf J et al.·Forensic Sci Int Genet
2026
Genome-wide association study of multiethnic nonsyndromic orofacial cleft families identifies novel loci specific to family and phenotypic subtypes.
Mukhopadhyay N et al.·Genet Epidemiol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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