POTEC

Chr 18

POTE ankyrin domain family member C

Also known as: A26B2, CT104.6, POTE-18, POTE18

POTEC encodes a POTE ankyrin domain family member protein of unknown function. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with intellectual disability, hypotonia, and seizures. The gene shows minimal constraint against loss-of-function variants, suggesting tolerance to such changes in the general population.

0
Active trials
2
Pubs (1 yr)
64
P/LP submissions
P/LP missense
1.26
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryPOTEC
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 unique Pathogenic / Likely Pathogenic· 8 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.26LOEUF
pLI 0.000
Z-score 0.67
OE 0.84 (0.571.26)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.87Z-score
OE missense 1.16 (1.051.28)
282 obs / 243.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.84 (0.571.26)
00.351.4
Missense OE1.16 (1.051.28)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 17 / 20.2Missense obs/exp: 282 / 243.9Syn Z: -0.20
DN
0.78top 25%
GOF
0.84top 5%
LOF
0.2777th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

78 submitted variants in ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic1
VUS8
Likely Benign4
Benign2
61
Pathogenic
1
Likely Pathogenic
8
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
61
Likely Pathogenic
1
VUS
8
Likely Benign
4
Benign
2
Total76

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

POTEC · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC