KATNB1

Chr 16AR

katanin regulatory subunit B1

Also known as: KAT, LIS6

NCBI Gene: 10300ENSG00000140854UniProt: Q9BVA0

Microtubules, polymers of alpha and beta tubulin subunits, form the mitotic spindle of a dividing cell and help to organize membranous organelles during interphase. Katanin is a heterodimer that consists of a 60 kDa ATPase (p60 subunit A 1) and an 80 kDa accessory protein (p80 subunit B 1). The p60 subunit acts to sever and disassemble microtubules, while the p80 subunit targets the enzyme to the centrosome. Katanin is a member of the AAA family of ATPases. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Lissencephaly 6, with microcephalyMIM #616212
AR
440
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KATNB1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 148 VUS of 440 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.61LOEUF
pLI 0.000
Z-score 3.45
OE 0.40 (0.26–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.64Z-score
OE missense 0.78 (0.71–0.85)
345 obs / 441.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.26–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.71–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 15 / 37.9Missense obs/exp: 345 / 441.7Syn Z: 0.07

ClinVar Variant Classifications

440 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic6
VUS148
Likely Benign194
Benign52
Conflicting13
27
Pathogenic
6
Likely Pathogenic
148
VUS
194
Likely Benign
52
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
4
18
0
27
Likely Pathogenic
2
0
4
0
6
VUS
0
129
18
1
148
Likely Benign
0
19
85
90
194
Benign
0
3
39
10
52
Conflicting
—13
Total7155164101440

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

View in ClinVar →

Protein Context — Lollipop Plot

KATNB1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

KATNB1-related complex cerebral malformations

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Lissencephaly 6, with microcephaly

MIM #616212

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KATNB1 in the human testis and its genetic variants in fertile and oligoasthenoteratozoospermic infertile men.
O'Donnell L et al.·Andrology
2014
A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation.
Yigit G et al.·Am J Med Genet A
2016Case report
Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors.
Mishra-Gorur K et al.·Neuron
2014
Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF.
Huffman JE et al.·Blood
2015Meta-analysis
Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics.
Jin M et al.·Sci Rep
2017
Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples.
Peluso F et al.·Genes (Basel)
2021
Subcortical heterotopic gray matter brain malformations: Classification study of 107 individuals.
Oegema R et al.·Neurology
2019
Klebsiella pneumoniae disassembles host microtubules in lung epithelial cells.
Chua MD et al.·Cell Microbiol
2019
A 16q12.2q21 deletion identified in a patient with developmental delay, epilepsy, short stature, and distinctive features.
Yamamoto T et al.·Congenit Anom (Kyoto)
2016Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools