KATNB1

protein-coding

katanin regulatory subunit B1, the group of WD repeat domain containing

Gene summary

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]

MANE transcript

NM_005886.3

Inheritance

ClinVar variants

P:18U:146B:136

Top phenotype

Lissencephaly 6, with microcephaly

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr16:57,735,739-57,757,244

External References & Databases

Ensembl (ENSG00000140854)

Transcript & Mutation Effects

hg38 • Region Span ~21.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lissencephaly 6 with microcephalyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014534

Submitter: Illumina

lissencephaly 6 with microcephalyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014534

Submitter: Ambry Genetics

lissencephaly 6 with microcephalySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014534

Submitter: Labcorp Genetics (formerly Invitae)

lissencephaly 6 with microcephalySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014534

Submitter: PanelApp Australia

lissencephaly 6 with microcephalySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014534

Submitter: G2P

Clinical Genomic Database (CGD)

Lissencephaly 6, with microcephalyAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25521378; 25521379

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KATNB1 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 285

Inborn genetic diseasesTotal: 107

not specifiedTotal: 36

KATNB1-related disorderTotal: 34

Lissencephaly 6 with microcephalyTotal: 22

Intellectual disabilityTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005886.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	98 clinvar	6 clinvar	106
missense	3 clinvar	1 clinvar	140 clinvar	29 clinvar	3 clinvar	176
nonsense	1 clinvar	3 clinvar	1 clinvar			5
start loss	1 clinvar					1
frameshift	4 clinvar	1 clinvar				5
splice donor/acceptor (+/-2bp)	2 clinvar	2 clinvar	3 clinvar			7
Total	11	7	146	127	9	300

Highest pathogenic variant AF is 0.000010555309

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005886.3	RefSeq	NP_005877.2	19	MANE Select
ENST00000379661.8	Ensembl	ENSP00000368982.3	19	MANE Select
ENST00000562592.5	Ensembl	ENSP00000455350.1	7	Standard
ENST00000563462.1	Ensembl	ENSP00000457334.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
katnb1	Danio rerio	Structure: midbrain Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

katnb1

Danio rerio

Structure: midbrain

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein targeting
microtubule depolymerization
negative regulation of microtubule depolymerization
mitotic chromosome movement towards spindle pole
positive regulation of cell death

Molecular Function

protein binding
microtubule binding
microtubule-severing ATPase activity
protein heterodimerization activity
dynein complex binding

Cellular Component

spindle pole
nucleus
cytoplasm
centrosome
spindle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379661
Coding exons: 19
Length: 21521
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.64	345	442	0.781	0.0000302	4243
Missense (PolyPhen)		121	170.91	0.70797		1597
Synonymous	0.0694	185	186	0.994	0.0000137	1308
Loss of Function	3.45	15	37.9	0.396	0.00000208	382

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth. {ECO:0000255|HAMAP-Rule:MF_03022, ECO:0000269|PubMed:10751153}.;
Disease: DISEASE: Lissencephaly 6, with microcephaly (LIS6) [MIM:616212]: A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS6 features include hypoplasia of the corpus callosum, severe microcephaly and developmental delay. {ECO:0000269|PubMed:25521378, ECO:0000269|PubMed:25521379}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.515
RVIS EVS: -0.51
RVIS percentile EVS: 21.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.905

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium