KATNB1

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

Basic information

Region (hg38): 16:57735739-57757244

Links

ENSG00000140854 ∙ NCBI:10300 ∙ OMIM:602703 ∙ HGNC:6217 ∙ Uniprot:Q9BVA0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lissencephaly 6 with microcephaly (Moderate), mode of inheritance: AR
• lissencephaly 6 with microcephaly (Strong), mode of inheritance: AR
• lissencephaly 6 with microcephaly (Strong), mode of inheritance: AR
• microlissencephaly (Supportive), mode of inheritance: AR
• lissencephaly 6 with microcephaly (Definitive), mode of inheritance: AR
• lissencephaly 6 with microcephaly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lissencephaly 6, with microcephaly	AR	General	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	Neurologic	25521378; 25521379

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KATNB1 gene.

• not_provided (259 variants)
• Inborn_genetic_diseases (96 variants)
• KATNB1-related_disorder (28 variants)
• Lissencephaly_6_with_microcephaly (19 variants)
• not_specified (19 variants)
• Intellectual_disability (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KATNB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005886.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	84	8	93
missense	3	1	120	29	3	156
nonsense		1				1
start loss	1					1
frameshift	4	1				5
splice donor/acceptor (+/-2bp)	1	1				2
Total	9	4	121	113	11

Highest pathogenic variant AF is 0.0000105553

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KATNB1	protein_coding	protein_coding	ENST00000379661	19	21521

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000145	1.00	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	345	442	0.781	0.0000302	4243
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.0000468	0.0000462
European (Non-Finnish)	0.000169	0.000167
Middle Eastern	0.000381	0.000381
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.314
• hipred: Y
• hipred_score: 0.639
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.905

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Katnb1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; liver/biliary system phenotype; embryo phenotype; hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype

Zebrafish Information Network

• Gene name: katnb1
• Affected structure: midbrain
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: protein targeting;microtubule depolymerization;negative regulation of microtubule depolymerization;mitotic chromosome movement towards spindle pole;positive regulation of cell death;positive regulation of neuron projection development;positive regulation of microtubule depolymerization;microtubule severing;cell division
• Cellular component: spindle pole;nucleus;cytoplasm;centrosome;spindle;cytosol;microtubule;plasma membrane;katanin complex;microtubule cytoskeleton;membrane;growth cone;midbody;neuronal cell body
• Molecular function: protein binding;microtubule binding;microtubule-severing ATPase activity;protein heterodimerization activity;dynein complex binding