KATNB1

Chr 16AR

katanin regulatory subunit B1

Also known as: KAT, LIS6

NCBI Gene: 10300 ENSG00000140854 UniProt: Q9BVA0 OMIM: 602703

The KATNB1 gene encodes the p80 regulatory subunit of katanin, a microtubule-severing enzyme where the p80 subunit targets the enzyme to the centrosome while the p60 subunit performs the ATPase-dependent microtubule severing. Biallelic mutations cause lissencephaly 6 with microcephaly, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted microtubule dynamics affecting neuronal migration and brain development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.611 OMIM phenotype

Clinical Summary— KATNB1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 145 VUS of 438 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.000

Z-score 3.45

OE 0.40 (0.26–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.64Z-score

OE missense 0.78 (0.71–0.85)

345 obs / 441.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.26–0.61)

0≤0.351.4

Missense OE?0.78 (0.71–0.85)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 15 / 37.9Missense obs/exp: 345 / 441.7Syn Z: 0.07

ClinVar Variant Classifications

438 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic4

VUS145

Likely Benign194

Benign52

Conflicting13

Pathogenic

Likely Pathogenic

145

VUS

194

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	4	0	0	10
Likely Pathogenic	4	0	0	0	4
VUS	0	133	11	1	145
Likely Benign	0	19	85	90	194
Benign	0	3	39	10	52
Conflicting	—				13
Total	10	159	135	101	418

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

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21 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap KATNB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →