KATNA1

Summary

KATNA1 (katanin catalytic subunit A1, HGNC:6216) is a protein-coding gene on chromosome 6q25.1, encoding Katanin p60 ATPase-containing subunit A1 (O75449). Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner.

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. This gene encodes the p80 subunit. This protein is a member of the AAA family of ATPases. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 11104 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 78 total
• Druggable target: yes
• MANE Select transcript: NM_007044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6216
Approved symbol	KATNA1
Name	katanin catalytic subunit A1
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186625
Ensembl biotype	protein_coding
OMIM	606696
Entrez	11104

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 20 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000335643, ENST00000335647, ENST00000367411, ENST00000420200, ENST00000444282, ENST00000470620, ENST00000481905, ENST00000494504, ENST00000854048, ENST00000854049, ENST00000854050, ENST00000854051, ENST00000854052, ENST00000854053, ENST00000854054, ENST00000854055, ENST00000928414, ENST00000928415, ENST00000928416, ENST00000928417, ENST00000928418, ENST00000968059, ENST00000968060

RefSeq mRNA: 2 — MANE Select: NM_007044 NM_001204076, NM_007044

CCDS: CCDS5217, CCDS56456

Canonical transcript exons

ENST00000367411 — 11 exons

Exon	Start	End
ENSE00001422379	149648469	149648714
ENSE00003480429	149604661	149604782
ENSE00003485171	149601594	149601752
ENSE00003498884	149623103	149623283
ENSE00003504546	149597507	149597641
ENSE00003504699	149603268	149603373
ENSE00003548553	149598224	149598350
ENSE00003892282	149597063	149597189
ENSE00003892367	149594873	149595234
ENSE00003893341	149632759	149632916
ENSE00003894077	149638386	149638560

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 95.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7590 / max 205.5660, expressed in 1800 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76134	4.3881	1647
76135	3.6538	1597
76132	3.4345	1108
76133	3.2826	1503

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.79	gold quality
secondary oocyte	CL:0000655	95.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.71	gold quality
male germ cell	CL:0000015	94.33	gold quality
left testis	UBERON:0004533	93.93	gold quality
right testis	UBERON:0004534	93.85	gold quality
oocyte	CL:0000023	92.73	gold quality
testis	UBERON:0000473	92.59	gold quality
calcaneal tendon	UBERON:0003701	91.99	gold quality
pigmented layer of retina	UBERON:0001782	91.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.00	gold quality
gastrocnemius	UBERON:0001388	88.98	gold quality
muscle of leg	UBERON:0001383	88.56	gold quality
descending thoracic aorta	UBERON:0002345	87.89	gold quality
mucosa of stomach	UBERON:0001199	87.78	gold quality
tibial artery	UBERON:0007610	87.76	gold quality
popliteal artery	UBERON:0002250	87.75	gold quality
left ovary	UBERON:0002119	87.53	gold quality
aorta	UBERON:0000947	87.42	gold quality
tendon	UBERON:0000043	87.22	gold quality
thoracic aorta	UBERON:0001515	87.19	gold quality
ascending aorta	UBERON:0001496	87.12	gold quality
monocyte	CL:0000576	87.03	gold quality
mononuclear cell	CL:0000842	86.84	gold quality
leukocyte	CL:0000738	86.80	gold quality
ventricular zone	UBERON:0003053	86.74	gold quality
ganglionic eminence	UBERON:0004023	86.69	gold quality
right ovary	UBERON:0002118	86.64	gold quality
ectocervix	UBERON:0012249	86.62	gold quality
body of uterus	UBERON:0009853	86.49	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting KATNA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-15B-3P	97.85	66.68	974

Literature-anchored findings (GeneRIF, showing 15)

• LAPSER1 C terminal domain inhibits katanin(p80/p60)-mediated microtubule severing in vitro. (PMID:18490357)
• A common substrate recognition mode conserved between katanin p60 and VPS4 governs microtubule severing and membrane skeleton reorganization (PMID:20339000)
• Katanin p60 was aberrantly expressed during prostate cancer progression. The elevated katanin p60 expression may contribute to cancer cell metastasis via a stimulatory effect on cell motility. (PMID:21681775)
• Data propose a model in which spatial rearrangement of the p60 katanin N-terminal domain relative to the C-terminal AAA domain may be important for productive ATP hydrolysis towards MT-severing. (PMID:22325007)
• analysis of spastin’s microtubule-binding properties and comparison with katanin (PMID:23272056)
• Katanin Severing and Binding Microtubules Are Inhibited by Tubulin Carboxy Tails (PMID:26682813)
• CAMSAP3 precisely coordinates with dynein and katanin to regulate the microtubule detachment process. (PMID:28386021)
• ASPM-katanin complex controls microtubule disassembly at spindle poles and that misregulation of this process can lead to microcephaly. (PMID:28436967)
• targeting an active version of katanin p60 to the kinetochore can reduce the fidelity of achieving full chromosome alignment in metaphase and could serve as a microtubule disruption tool for the future. (PMID:30176123)
• structures of the apo and ATPgammaS-bound states of the catalytic AAA domain of human katanin p60 at 3.0 and 2.9 A resolution, respectively, are reported. (PMID:30699360)
• In this study, we identified the main regulatory region of KATNA1 gene encoding katanin-p60 as 5’ UTR, which has a key role for its expression, and showed Elk1 binding to KATNA1. Furthermore, we identified that Elk1 decreased katanin-p60 and spastin protein expressions, while mRNA levels were increased upon Elk1 overexpression. (PMID:30789974)
• Katanin P60: a potential biomarker for lymph node metastasis and prognosis for non-small cell lung cancer. (PMID:32631334)
• Katanin P60 and P80 in papillary thyroid carcinoma patients: Indicators for exacerbated tumor features and worse disease-free survival. (PMID:33274499)
• A chemical genetics approach to examine the functions of AAA proteins. (PMID:33782614)
• SUMOylation of microtubule-cleaving enzyme KATNA1 promotes microtubule severing and neurite outgrowth. (PMID:35868557)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	katna1	ENSDARG00000021827
mus_musculus	Katna1	ENSMUSG00000019794
rattus_norvegicus	Katna1	ENSRNOG00000014996
drosophila_melanogaster	Fign	FBGN0031519
drosophila_melanogaster	kat-60L1	FBGN0037375
drosophila_melanogaster	Kat60	FBGN0040208
caenorhabditis_elegans	mei-1	WBGENE00003183
caenorhabditis_elegans		WBGENE00017981

Paralogs (9): SPAST (ENSG00000021574), KATNAL1 (ENSG00000102781), VPS4B (ENSG00000119541), FIGNL1 (ENSG00000132436), VPS4A (ENSG00000132612), ATAD1 (ENSG00000138138), KATNAL2 (ENSG00000167216), FIGN (ENSG00000182263), FIGNL2 (ENSG00000261308)

Protein

Protein identifiers

Katanin p60 ATPase-containing subunit A1 — O75449 (reviewed: O75449)

Alternative names: p60 katanin

All UniProt accessions (3): B7ZBC8, B7ZBC9, O75449

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner. 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.

Subunit / interactions. Can homooligomerize into hexameric rings, which may be promoted by interaction with microtubules. Interacts with KATNB1, which may serve as a targeting subunit. Interacts with ASPM; the katanin complex formation KATNA1:KATNB1 is required for the association of ASPM. Interacts with dynein and NDEL1. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins (EDVP complex). Interacts with KLHL42 (via the kelch domains). Interacts with CUL3; the interaction is enhanced by KLHL42. Interacts with KATNB1 and KATNBL1. Interacts with CAMSAP2 and CAMSAP3; leading to regulate the length of CAMSAP-decorated microtubule stretches.

Subcellular location. Cytoplasm. Midbody. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Spindle.

Post-translational modifications. Phosphorylation by DYRK2 triggers ubiquitination and subsequent degradation. Ubiquitinated by the BCR(KLHL42) E3 ubiquitin ligase complex, leading to its proteasomal degradation. Ubiquitinated by the EDVP E3 ligase complex and subsequently targeted for proteasomal degradation.

Activity regulation. ATPase activity is stimulated by microtubules, which promote homooligomerization. ATP-dependent microtubule severing is stimulated by interaction with KATNB1.

Domain organisation. The N-terminus is sufficient for interaction with microtubules, although high affinity binding to microtubules also requires an intact C-terminal domain and ATP, which promotes oligomerization.

Similarity. Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O75449-1	1	yes
O75449-2	2

RefSeq proteins (2): NP_001191005, NP_008975* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR015415	Spast_Vps4_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR028596	KATNA1	Family
IPR041569	AAA_lid_3	Domain
IPR048611	KATNA1_MIT	Domain
IPR048612	KTNA1_AAA_dom	Domain
IPR050304	MT-severing_AAA_ATPase	Family

Pfam: PF00004, PF09336, PF17862, PF21126

Enzyme classification (BRENDA):

• EC 5.6.1.1 — microtubule-severing ATPase (BRENDA: 21 organisms, 29 substrates, 57 inhibitors, 16 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0003–2.94	16

UniProt features (46 total): helix 17, strand 8, region of interest 4, modified residue 4, splice variant 3, mutagenesis site 3, turn 3, compositionally biased region 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5ZQM	X-RAY DIFFRACTION	2.9
5ZQL	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75449-F1	75.36	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 249–256

Post-translational modifications (4): 133, 170, 42, 109

Mutagenesis-validated functional residues (3):

Position	Phenotype
255	abolishes atp dependent microtubule severing activity and localization to spindle poles.
308	abolishes atp dependent microtubule severing activity and localization to spindle poles; when associated with n-309.
309	abolishes atp dependent microtubule severing activity and localization to spindle poles; when associated with n-308.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, PUJANA_CHEK2_PCC_NETWORK, chr6q25, FOSTER_TOLERANT_MACROPHAGE_UP, FISCHER_G2_M_CELL_CYCLE, GOCC_CENTROSOME, PEART_HDAC_PROLIFERATION_CLUSTER_DN, FISCHER_DREAM_TARGETS, PUJANA_BRCA_CENTERED_NETWORK, VANTVEER_BREAST_CANCER_ESR1_DN, PID_LIS1_PATHWAY, GOCC_SPINDLE, TGGAAA_NFAT_Q4_01

GO Biological Process (4): cytoplasmic microtubule organization (GO:0031122), microtubule severing (GO:0051013), cell division (GO:0051301), microtubule cytoskeleton organization (GO:0000226)

GO Molecular Function (8): ATP binding (GO:0005524), microtubule binding (GO:0008017), microtubule severing ATPase activity (GO:0008568), ATP hydrolysis activity (GO:0016887), protein heterodimerization activity (GO:0046982), nucleotide binding (GO:0000166), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (11): spindle pole (GO:0000922), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), microtubule (GO:0005874), katanin complex (GO:0008352), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), mitotic spindle pole (GO:0097431), cytoskeleton (GO:0005856), mitotic spindle (GO:0072686)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule cytoskeleton organization	3
cellular anatomical structure	3
ATP-dependent activity	2
spindle	2
microtubule organizing center	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
supramolecular fiber organization	1
cellular process	1
cytoskeleton organization	1
microtubule-based process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
polypeptide conformation or assembly isomerase activity	1
catalytic activity, acting on a protein	1
microtubule destabilizing activity	1
ribonucleoside triphosphate phosphatase activity	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
centriole	1
polymeric cytoskeletal fiber	1
microtubule associated complex	1
cytoskeleton	1
spindle pole	1
mitotic spindle	1

Protein interactions and networks

STRING

2542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KATNA1	KATNB1	Q9BVA0	987
KATNA1	LZTS2	Q9BRK4	821
KATNA1	KATNBL1	Q9H079	744
KATNA1	NDEL1	Q9GZM8	740
KATNA1	ASPM	Q8IZT6	668
KATNA1	NDE1	Q9NXR1	597
KATNA1	TRIM13	O60858	583
KATNA1	SLITRK1	Q96PX8	580
KATNA1	TUBG1	P23258	578
KATNA1	KIF18A	Q8NI77	560
KATNA1	PAFAH1B2	P68402	549
KATNA1	LUZP1	Q86V48	528
KATNA1	ENTHD1	Q8IYW4	520
KATNA1	PCMT1	P22061	510
KATNA1	CDK5	Q00535	510

IntAct

46 interactions, top by confidence:

A	B	Type	Score
KATNB1	KATNA1	psi-mi:“MI:0915”(physical association)	0.770
KATNBL1	KATNA1	psi-mi:“MI:0915”(physical association)	0.770
KATNA1	KATNB1	psi-mi:“MI:0915”(physical association)	0.770
KATNBL1	KATNA1	psi-mi:“MI:0914”(association)	0.770
KATNA1	KATNB1	psi-mi:“MI:0914”(association)	0.770
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
PFDN1	PFDN6	psi-mi:“MI:0914”(association)	0.640
ARIH1	SPOP	psi-mi:“MI:0914”(association)	0.530
KATNA1	CCT7	psi-mi:“MI:0914”(association)	0.530
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
KATNA1	KATNBL1	psi-mi:“MI:0914”(association)	0.350
ASPM	KIF2A	psi-mi:“MI:0914”(association)	0.350
ASPM	KATNA1	psi-mi:“MI:0914”(association)	0.350
KATNAL1	CDK1	psi-mi:“MI:0914”(association)	0.350
KATNA1	AURKA	psi-mi:“MI:0914”(association)	0.350
KATNBL1	MACF1	psi-mi:“MI:0914”(association)	0.350
KATNB1	TUBA8	psi-mi:“MI:0914”(association)	0.350
ASB3	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
INPP5K	PES1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
KATNIP		psi-mi:“MI:0914”(association)	0.350

BioGRID (106): KATNA1 (Affinity Capture-MS), KATNA1 (Co-fractionation), KATNA1 (Reconstituted Complex), KATNA1 (Biochemical Activity), KATNA1 (Proximity Label-MS), KATNA1 (Proximity Label-MS), CAPN1 (Affinity Capture-MS), MAPT (Affinity Capture-MS), SRSF2 (Affinity Capture-MS), SRSF3 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS), SRPR (Affinity Capture-MS), USP1 (Affinity Capture-MS), AKR7A2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMA9, A2VDN5, A8QFF6, A8XV40, A9RA82, B2RYN7, B3EX35, B3M301, B4QSF0, B4USW8, B5X3X5, B7NZ88, B7PXE3, F4IAE9, O14114, O15381, O16299, O59824, O75449, P34808, P54816, Q05AS3, Q0IIR9, Q1HGK7, Q3B8D5, Q4R407, Q5RDX4, Q5RII9, Q5U3S1, Q5XIK7, Q5ZK92, Q60QD1, Q6AZT2, Q6E0V2, Q6NW58, Q6P158, Q6PL18, Q719N1, Q8CDM1, Q8IYT4

Diamond homologs: A0JMA9, A2VDN5, A4IHT0, A8QFF6, A8XV40, A9RA82, B2RYN7, B3EX35, B3M301, B3P8A3, B4G437, B4HGG6, B4JII0, B4K799, B4M0H8, B4NBP4, B4PL32, B4QSF0, B4USW8, B5X3X5, B7NZ88, B7PXE3, D0FH76, D2VS83, F2Z6D2, F4JEX5, F6QV99, O05209, O16299, O28972, O43078, O61577, O75351, O75449, P25694, P34808, P39955, P40328, P46467, P52917

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
DYRK2	“down-regulates quantity by destabilization”	KATNA1	phosphorylation
KATNB1	“up-regulates quantity by stabilization”	KATNA1	binding
KATNA1	“up-regulates activity”	KATNB1	binding
EDVP	“down-regulates quantity by destabilization”	KATNA1	polyubiquitination
KATNA1	down-regulates	Microtubule_polimerization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Prefoldin mediated transfer of substrate to CCT/TriC	6	98.5×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	16.8×	2e-04
cell division	6	7.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1561 predictions. Top by Δscore:

Variant	Effect	Δscore
6:149595239:G:C	acceptor_gain	1.0000
6:149595239:G:GC	acceptor_gain	1.0000
6:149595240:T:C	acceptor_gain	1.0000
6:149595240:T:TC	acceptor_gain	1.0000
6:149595241:T:C	acceptor_gain	1.0000
6:149595241:T:TC	acceptor_gain	1.0000
6:149595242:T:C	acceptor_gain	1.0000
6:149595242:T:TC	acceptor_gain	1.0000
6:149595246:G:C	acceptor_gain	1.0000
6:149595246:G:GC	acceptor_gain	1.0000
6:149595247:T:C	acceptor_gain	1.0000
6:149595247:T:TC	acceptor_gain	1.0000
6:149597190:C:CC	acceptor_gain	1.0000
6:149597502:GATA:G	donor_loss	1.0000
6:149597504:TACC:T	donor_loss	1.0000
6:149597505:A:C	donor_loss	1.0000
6:149597506:C:CA	donor_loss	1.0000
6:149597638:ACAC:A	acceptor_gain	1.0000
6:149597639:CAC:C	acceptor_gain	1.0000
6:149597639:CACC:C	acceptor_gain	1.0000
6:149597642:C:CC	acceptor_gain	1.0000
6:149597647:A:AC	acceptor_gain	1.0000
6:149597653:G:C	acceptor_gain	1.0000
6:149597653:G:GC	acceptor_gain	1.0000
6:149598226:T:TA	donor_gain	1.0000
6:149598348:AGCC:A	acceptor_loss	1.0000
6:149598349:GCC:G	acceptor_loss	1.0000
6:149598350:CCTAA:C	acceptor_loss	1.0000
6:149598351:CTAA:C	acceptor_loss	1.0000
6:149601614:CAAG:C	donor_gain	1.0000

AlphaMissense

3226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:149597082:C:G	D420H	1.000
6:149597171:A:G	L390P	1.000
6:149597577:A:C	N360K	1.000
6:149597577:A:T	N360K	1.000
6:149597581:G:A	T359I	1.000
6:149597584:G:T	A358D	1.000
6:149598238:A:G	L334P	1.000
6:149598241:A:G	L333P	1.000
6:149598325:A:T	I305K	1.000
6:149601600:A:C	F294L	1.000
6:149601600:A:T	F294L	1.000
6:149601602:A:G	F294L	1.000
6:149601631:C:T	G284E	1.000
6:149601632:C:G	G284R	1.000
6:149601632:C:T	G284R	1.000
6:149601694:G:T	A263D	1.000
6:149601701:C:G	A261P	1.000
6:149601706:G:T	A259D	1.000
6:149601721:C:T	G254E	1.000
6:149601722:C:A	G254W	1.000
6:149601727:C:T	G252D	1.000
6:149601736:C:T	G249D	1.000
6:149601737:C:G	G249R	1.000
6:149601745:A:G	L246P	1.000
6:149604662:A:G	W208R	1.000
6:149604662:A:T	W208R	1.000
6:149638507:C:G	R14P	1.000
6:149595211:C:G	R434T	0.999
6:149595229:G:T	A428E	0.999
6:149595230:C:G	A428P	0.999

dbSNP variants (sampled 300 via entrez): RS1000002191 (6:149623881 A>C), RS1000012406 (6:149630900 A>T), RS1000174553 (6:149618321 T>C), RS1000246908 (6:149636823 G>A), RS1000263815 (6:149618605 A>G), RS1000264037 (6:149618602 C>G), RS1000361329 (6:149648844 G>A,C), RS1000468814 (6:149611765 C>A,G,T), RS1000482911 (6:149624253 G>C), RS1000490126 (6:149624082 A>AT), RS1000649610 (6:149619882 C>G,T), RS1000780954 (6:149624356 C>A,T), RS1000804202 (6:149643589 C>A), RS1000856667 (6:149643936 C>T), RS1000882563 (6:149598723 C>T)

Disease associations

OMIM: gene MIM:606696 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003775_6	Lung cancer	1.000000e-07
GCST004635_15	Testicular germ cell tumor	2.000000e-09
GCST010702_29	Subcortical volume (MOSTest)	7.000000e-11
GCST010703_317	Brain morphology (MOSTest)	7.000000e-22

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879856 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — AAA ATPases

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.74	Kd	1815	nM	CHEMBL5560224
5.04	Kd	9155	nM	CHEMBL4561563

PubChem BioAssay actives

2 with measured affinity, of 27 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-methyl-5-[3-(3,4,5-trimethoxyphenyl)imidazo[4,5-b]pyridin-5-yl]aniline	2086103: Binding affinity to N-terminal human Katanin p60 (8 to 229 residues) expressed in Escherichia coli Rosetta (DE3) assessed as dissociation constant by SPR analysis	kd	1.8150	uM
6-(3-hydroxy-4-methoxyphenyl)-2-oxo-1-(3,4,5-trimethoxyphenyl)-3H-imidazo[4,5-c]pyridine-4-carboxamide	2086103: Binding affinity to N-terminal human Katanin p60 (8 to 229 residues) expressed in Escherichia coli Rosetta (DE3) assessed as dissociation constant by SPR analysis	kd	9.1550	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Dimethyl Sulfoxide	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3860462	Binding	Induction of katanin p60 subunit-mediated JNK signaling pathway activation in human NCI-H1975 cells assessed as increase in JNK phosphorylation at T183/Y185 and T221/Y223 residues at 300 nM after 9 hrs by phospho-kinase antibody array metho	Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.