TANC2

Chr 17AD

tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2

Also known as: IDDALDS, ROLSA, rols

NCBI Gene: 26115 ENSG00000170921 UniProt: Q9HCD6 OMIM: 615047

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in dense core granule cytoskeletal transport; regulation of dendritic spine development; and regulation of dendritic spine morphogenesis. Predicted to act upstream of or within in utero embryonic development. Located in dendritic spine. Implicated in intellectual developmental disorder with autistic features and language delay, with or without seizures. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.161 OMIM phenotype

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

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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

57 unique Pathogenic / Likely Pathogenic· 492 VUS of 722 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?

0.16LOEUF

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?

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?

LoF OE?0.09 (0.05–0.16)

0≤0.351.4

Missense OE?0.80 (0.76–0.85)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

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

This gene — mechanism propensity

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

722 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic37

VUS492

Likely Benign126

Benign11

Conflicting12

Pathogenic

Likely Pathogenic

492

VUS

126

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	0	0	0	20
Likely Pathogenic	33	0	4	0	37
VUS	13	456	16	7	492
Likely Benign	0	48	9	69	126
Benign	0	1	2	8	11
Conflicting	—				12
Total	66	505	31	84	698

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap TANC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →