KATNAL2

protein-coding

katanin catalytic subunit A1 like 2, the group of AAA ATPases

Gene summary

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]

MANE transcript

NM_001387690.1

Inheritance

AD, AR

ClinVar variants

U:95B:32

Top phenotype

KATNAL2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr18:46,917,492-47,103,478

External References & Databases

Ensembl (ENSG00000167216)

Transcript & Mutation Effects

hg38 • Region Span ~186.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

complex neurodevelopmental disorderNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: ClinGen

Variants in *KATNAL2* have been reported in numerous individuals with complex neurodevelopmental disorders, including autism spectrum disorder (PMIDs: 22495306, 22495309, 22495311, 25363760, 25621899, 28191889, 30504930, 31209962, 31398340, 31981491, 32094338) and intellectual disability (PMIDs: 28191889, 31209962, 32094338); the first reports were published in autism in 2012 (PMIDs: 22495306, 22495309, 22495311). At least 32 variants have been reported (3 nonsense, 5 frameshift, 5 splice site, 17 missense, and 2 CNV deletions); 4 were *de novo*, 12 inherited (including 7 truncating variants), and 6 were of unknown inheritance. It is unlikely that these variants are the cause for the neurodevelopmental disorders present in these individuals. In many of the reported cases, the variants are inherited from parents that are either reportedly unaffected or have no phenotype information, they do not segregate with disease (PMIDs: 25621899, 28191889, 32094338), or are present in population databases at frequencies too high to be causative of disease (PMIDs: 25363760, 28191889, 31209962). In addition, *KATNAL2* truncating variants have been reported in control subjects (PMIDs: 25363760, 30208311, 31981491). Further, per data from gnomAD, *KATNAL2* appears to be tolerant of variation in general - the gene is not constrained for either missense or protein truncating variants. This makes it difficult to discern a potential disease mechanism and raises the question of whether the variants reported in the affected individuals occurred just by chance. In summary, the evidence supporting the relationship between *KATNAL2* and autosomal dominant complex neurodevelopmental disorders has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role *KATNAL2* plays in this disease. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on May 20, 2020 (SOP Version 7). As of August 2026, this record underwent administrative updates to update scoring to be consistent with SOP Version 12. No new evidence has been reviewed or added.

male infertilityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005372

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KATNAL2 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 322

not providedTotal: 52

KATNAL2-related disorderTotal: 34

See casesTotal: 4

ELOA3P-related conditionTotal: 2

Prostate cancerTotal: 1

KATNAL2-related autismTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001387690.1. 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				17 clinvar	1 clinvar	18
missense			88 clinvar	12 clinvar	2 clinvar	102
nonsense			3 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	95	29	3	127

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 73 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001387690.1	RefSeq	NP_001374619.1	16	MANE Select
ENST00000683218.1	Ensembl	ENSP00000508137.1	16	MANE Select
NM_001353899.1	RefSeq	NP_001340828.1	17	Standard
NM_001353900.1	RefSeq	NP_001340829.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cytoplasmic microtubule organization
microtubule severing

Molecular Function

protein binding
ATP binding
microtubule binding
microtubule-severing ATPase activity
isomerase activity

Cellular Component

spindle pole
nucleus
cytoplasm
spindle
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000245121
Coding exons: 14
Length: 130204
Individuals with no LoFs: 125644
Homozygous LoFs: 0
Heterozygous LoFs: 104
Defined: 125748
p: 0.000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.421	244	263	0.927	0.0000147	3030
Missense (PolyPhen)		75	101.52	0.73879		1188
Synonymous	-1.31	115	98.5	1.17	0.00000559	880
Loss of Function	2.29	14	26.8	0.522	0.00000142	319

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0026	0.0026	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00030	0.00029	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Severs microtubules in vitro in an ATP-dependent manner. This activity may promote rapid reorganization of cellular microtubule arrays. {ECO:0000255|HAMAP-Rule:MF_03025}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.208
RVIS EVS: -1.09
RVIS percentile EVS: 7.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.209

Gene Damage Prediction

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