TANC2

Chr 17AD

tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2

Also known as: IDDALDS, ROLSA, rols

The protein serves as a scaffolding protein in dendritic spines that recruits dense core vesicles to postsynaptic sites. Autosomal dominant mutations cause intellectual developmental disorder with autistic features and language delay, with or without seizures. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.161 OMIM phenotype
Clinical SummaryTANC2
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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.
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ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 356 VUS of 500 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

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 8.09
OE 0.09 (0.050.16)
Highly constrained

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

Missense Constraint
2.34Z-score
OE missense 0.80 (0.760.85)
900 obs / 1120.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.050.16)
00.351.4
Missense OE0.80 (0.760.85)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 8 / 91.5Missense obs/exp: 900 / 1120.8Syn Z: 0.86
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTANC2-related neurodevelopmental and psychiatric disordersLOFAD
DN
0.4488th %ile
GOF
0.4184th %ile
LOF
0.75top 10%

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

LOFprediction above median · 93% of P/LP variants are LoF · LOEUF 0.16

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

500 submitted variants in ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic26
VUS356
Likely Benign69
Benign4
Conflicting4
17
Pathogenic
26
Likely Pathogenic
356
VUS
69
Likely Benign
4
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
1
0
17
Likely Pathogenic
24
0
2
0
26
VUS
11
328
13
4
356
Likely Benign
0
26
4
39
69
Benign
0
0
0
4
4
Conflicting
4
Total513542047476

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC