KATNAL2

Chr 18

katanin catalytic subunit A1 like 2

NCBI Gene: 83473 ENSG00000167216 UniProt: Q8IYT4

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.

ResearchSummary from RefSeq, UniProt

Predicted to enable ATP hydrolysis activity. Predicted to be involved in meiotic spindle organization and microtubule severing. Located in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · complex neurodevelopmental disorder · AD · ClinGen 2020

evidence questions this relationship

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.29

OE 0.52 (0.34–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.42Z-score

OE missense 0.93 (0.83–1.03)

244 obs / 263.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.34–0.82)

0≤0.351.4

Missense OE?0.93 (0.83–1.03)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 14 / 26.8Missense obs/exp: 244 / 263.2Syn Z: -1.31

Background carrier burden — how many people carry a rare variant somewhere in KATNAL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

794 rare PASS variants

Rare truncating (LoF)

1 in 230

162 rare PASS variants

Rare synonymous (reference)

1 in 210

286 rare PASS variants

Rare missense and truncating variants are carried at similar rates in KATNAL2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 87	1 in 220
South Asian	~43k	1 in 51	1 in 220
Remaining (unassigned)	~30k	1 in 50	1 in 670
European (Finnish)	~27k	1 in 140	1 in 990
Admixed American	~22k	1 in 60	1 in 390
African / African American	~21k	1 in 65	1 in 350
East Asian	~20k	1 in 61	1 in 200
Ashkenazi Jewish	~13k	1 in 180	1 in 450
Middle Eastern	~2,884	1 in 75	≈ 1 in 710

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 16 coding exons well covered in gnomAD exomes; exons 3, 4, 11, 14 marginal. Genomes: 15 of 16 (exon 11 below).? see exons ↓