TATDN1

Chr 8

TatD DNase domain containing 1

Also known as: CDA11

The TATDN1 protein exhibits 3'-5' DNA exonuclease and AP endonuclease activities and plays an important role in chromosomal segregation and cell cycle progression during eye development via its DNA decatenation activity. Mutations cause autosomal recessive spastic paraplegia with optic atrophy and neuropathy (SPOAN syndrome), typically presenting in infancy with progressive spastic paraparesis, congenital optic atrophy, and peripheral neuropathy. The gene shows extreme intolerance to loss-of-function variants (pLI ~1), indicating that complete protein loss is likely incompatible with normal development.

Summary from RefSeq, UniProt
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0
Active trials
1
Pubs (1 yr)
54
P/LP submissions
0%
P/LP missense
1.58
LOEUF
DN
Mechanism· predicted
Clinical SummaryTATDN1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 48 VUS of 128 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.58LOEUF
pLI 0.000
Z-score -0.46
OE 1.11 (0.791.58)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.18Z-score
OE missense 1.04 (0.911.19)
155 obs / 148.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.11 (0.791.58)
00.351.4
Missense OE1.04 (0.911.19)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 22 / 19.8Missense obs/exp: 155 / 148.8Syn Z: 0.91
DN
0.6259th %ile
GOF
0.4874th %ile
LOF
0.4135th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

128 submitted variants in ClinVar

Classification Summary

Pathogenic54
VUS48
Likely Benign1
54
Pathogenic
48
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
0
0
0
VUS
0
42
6
0
48
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total042610103

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

View in ClinVar →

Protein Context — Lollipop Plot

TATDN1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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