KATNAL2

Chr 18

katanin catalytic subunit A1 like 2

The KATNAL2 protein severs microtubules in an ATP-dependent manner to promote reorganization of cellular microtubule arrays. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. This gene shows tolerance to loss-of-function variants in the general population.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
3
Pubs (1 yr)
45
P/LP submissions
0%
P/LP missense
0.82
LOEUF
DN
Mechanism· predicted
Clinical SummaryKATNAL2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDisputed

Disputed — evidence questions this relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 304 VUS of 466 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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.000
Z-score 2.29
OE 0.52 (0.340.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.42Z-score
OE missense 0.93 (0.831.03)
244 obs / 263.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.340.82)
00.351.4
Missense OE0.93 (0.831.03)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 14 / 26.8Missense obs/exp: 244 / 263.2Syn Z: -1.31
DN
0.79top 25%
GOF
0.4875th %ile
LOF
0.2775th %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

466 submitted variants in ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic2
VUS304
Likely Benign90
Benign16
Conflicting2
41
Pathogenic
2
Likely Pathogenic
304
VUS
90
Likely Benign
16
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
41
0
41
Likely Pathogenic
0
0
2
0
2
VUS
2
279
23
0
304
Likely Benign
0
38
28
24
90
Benign
1
5
7
3
16
Conflicting
2
Total332210127455

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

View in ClinVar →

Protein Context — Lollipop Plot

KATNAL2 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC