KATNB1

Summary

KATNB1 (katanin regulatory subunit B1, HGNC:6217) is a protein-coding gene on chromosome 16q21, encoding Katanin p80 WD40 repeat-containing subunit B1 (Q9BVA0). Participates in a complex which severs microtubules in an ATP-dependent manner. It is a selective cancer dependency (DepMap: 40.5% of cell lines).

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.

Source: NCBI Gene 10300 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lissencephaly 6 with microcephaly (Definitive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 437 total — 10 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 40.5% of screened cell lines
• MANE Select transcript: NM_005886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6217
Approved symbol	KATNB1
Name	katanin regulatory subunit B1
Location	16q21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000140854
Ensembl biotype	protein_coding
OMIM	602703
Entrez	10300

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 24 protein_coding, 4 retained_intron

ENST00000379661, ENST00000562542, ENST00000562592, ENST00000563127, ENST00000563462, ENST00000566611, ENST00000566726, ENST00000566785, ENST00000569018, ENST00000569627, ENST00000874405, ENST00000874406, ENST00000874407, ENST00000874408, ENST00000874409, ENST00000874410, ENST00000874411, ENST00000874412, ENST00000874413, ENST00000912654, ENST00000912655, ENST00000912656, ENST00000912657, ENST00000912658, ENST00000955861, ENST00000955862, ENST00000955863, ENST00000955864

RefSeq mRNA: 1 — MANE Select: NM_005886 NM_005886

CCDS: CCDS10788

Canonical transcript exons

ENST00000379661 — 20 exons

Exon	Start	End
ENSE00000945336	57752778	57752928
ENSE00000945337	57753077	57753267
ENSE00000945344	57755992	57756066
ENSE00001279093	57752530	57752601
ENSE00001518102	57756814	57757244
ENSE00001518124	57735770	57735855
ENSE00003467393	57741687	57741817
ENSE00003484130	57736978	57737283
ENSE00003487659	57753945	57753995
ENSE00003497203	57750827	57750927
ENSE00003509091	57755119	57755238
ENSE00003512890	57755841	57755917
ENSE00003520461	57751261	57751302
ENSE00003554197	57756356	57756472
ENSE00003600390	57744394	57744511
ENSE00003607359	57751641	57751724
ENSE00003617031	57754930	57754997
ENSE00003651138	57755345	57755494
ENSE00003680421	57753389	57753519
ENSE00003791466	57751940	57752055

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2541 / max 82.5033, expressed in 1783 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154417	8.0550	1762
154418	3.1387	1316
154420	0.0309	9
154421	0.0295	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	94.38	gold quality
right frontal lobe	UBERON:0002810	93.51	gold quality
right uterine tube	UBERON:0001302	93.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.04	gold quality
oocyte	CL:0000023	92.95	gold quality
prefrontal cortex	UBERON:0000451	92.90	gold quality
primary visual cortex	UBERON:0002436	91.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.93	gold quality
endothelial cell	CL:0000115	91.71	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.47	gold quality
frontal cortex	UBERON:0001870	91.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.40	gold quality
neocortex	UBERON:0001950	91.33	gold quality
cingulate cortex	UBERON:0003027	91.29	gold quality
left testis	UBERON:0004533	91.29	gold quality
secondary oocyte	CL:0000655	91.25	gold quality
anterior cingulate cortex	UBERON:0009835	91.20	gold quality
nucleus accumbens	UBERON:0001882	90.90	gold quality
skin of leg	UBERON:0001511	90.89	gold quality
right testis	UBERON:0004534	90.86	gold quality
cortical plate	UBERON:0005343	90.48	gold quality
cerebral cortex	UBERON:0000956	90.08	gold quality
caudate nucleus	UBERON:0001873	90.01	gold quality
putamen	UBERON:0001874	89.97	gold quality
skin of abdomen	UBERON:0001416	89.69	gold quality
telencephalon	UBERON:0001893	89.53	gold quality
testis	UBERON:0000473	89.45	gold quality
granulocyte	CL:0000094	89.37	gold quality
occipital lobe	UBERON:0002021	89.35	gold quality
epithelium of bronchus	UBERON:0002031	89.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELK1

miRNA regulators (miRDB)

20 targeting KATNB1, 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-4282	99.99	75.36	6408
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-1913	97.07	66.20	1417

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 40.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• LAPSER1 C terminal domain inhibits katanin(p80/p60)-mediated microtubule severing in vitro. (PMID:18490357)
• Cul3-deficient cells or Ctb9/KLHDC5-deficient cells show an increase in p60/katanin levels, indicating that Cul3/Ctb9/KLHDC5 is required for efficient p60/katanin removal (PMID:19261606)
• results suggest that variants in the KATNB1 gene are not commonly associated with OAT infertility in Australian men (PMID:25280067)
• results provide insight into the mechanisms by which KATNB1 mutations cause human cerebral cortical malformations, demonstrating its fundamental role during brain development. (PMID:25521378)
• results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development (PMID:25521379)
• Results indicate that microtubule-severing is complex and likely regulated by the concerted action of KATNB1 and KATNBL1. (PMID:26929214)
• The localization of KATNB1 in early round spermatids suggests an involvement in the formation of microtubule-based structures during spermiogenesis (manchette and flagellum). (PMID:27717557)
• these findings provide valuable insights into the pathogenesis of severe microlissencephaly, in which p80 and NuMA delineate a common pathway for neurogenesis and neuronal migration via microtubule organization at the centrosome/spindle pole (PMID:28079116)
• ASPM-katanin complex controls microtubule disassembly at spindle poles and that misregulation of this process can lead to microcephaly. (PMID:28436967)
• Katanin P80 expression positively correlated with lymph node metastasis and could abe a novel biomarker for prognosis in breast cancer patients. (PMID:30223388)
• Katanin P60 and P80 in papillary thyroid carcinoma patients: Indicators for exacerbated tumor features and worse disease-free survival. (PMID:33274499)
• WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation. (PMID:34137788)
• Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples. (PMID:34202629)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	katnb1	ENSDARG00000005456
mus_musculus	Katnb1	ENSMUSG00000031787
rattus_norvegicus	Katnb1	ENSRNOG00000014626
drosophila_melanogaster	kat80	FBGN0040207
caenorhabditis_elegans	F47G4.4	WBGENE00009825
caenorhabditis_elegans	F47G4.5	WBGENE00009826

Protein

Protein identifiers

Katanin p80 WD40 repeat-containing subunit B1 — Q9BVA0 (reviewed: Q9BVA0)

Alternative names: p80 katanin

All UniProt accessions (6): Q9BVA0, H3BPD8, H3BPK1, H3BT67, H3BTU7, H3BTV8

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with PAFAH1B1. Interacts with KATNA1. This interaction enhances the microtubule binding and severing activity of KATNA1 and also targets this activity to the centrosome. This interaction is weakly competed by KATNBL1 which has a lower affinity for it. Interacts with ASPM; the katanin complex formation KATNA1:KATNB1 is required for the association of ASPM. Interacts with dynein, microtubules and NDEL1. Interacts with KATNAL1; this interaction is weakly competed by KATNBL1 which has a lower affinity for it. Interacts with CAMSAP2 and CAMSAP3; leading to regulate the length of CAMSAP-decorated microtubule stretches.

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

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat KATNB1 family.

RefSeq proteins (1): NP_005877* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR026962	KTNB1	Family
IPR028021	Katanin_C-terminal	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400, PF13925

UniProt features (22 total): repeat 6, region of interest 5, sequence variant 4, sequence conflict 3, compositionally biased region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVA0-F1	79.58	0.53

Functional residue map

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

Post-translational modifications (1): 395

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 361 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CHROMOSOME_LOCALIZATION, GOBP_PROTEIN_TARGETING, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GGGTGGRR_PAX4_03, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MICROTUBULE_POLYMERIZATION_OR_DEPOLYMERIZATION

GO Biological Process (10): protein targeting (GO:0006605), microtubule depolymerization (GO:0007019), negative regulation of microtubule depolymerization (GO:0007026), mitotic chromosome movement towards spindle pole (GO:0007079), positive regulation of neuron projection development (GO:0010976), positive regulation of microtubule depolymerization (GO:0031117), cytoplasmic microtubule organization (GO:0031122), positive regulation of apoptotic process (GO:0043065), microtubule severing (GO:0051013), cell division (GO:0051301)

GO Molecular Function (5): microtubule binding (GO:0008017), protein heterodimerization activity (GO:0046982), ATPase regulator activity (GO:0060590), dynein complex binding (GO:0070840), protein binding (GO:0005515)

GO Cellular Component (17): spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), katanin complex (GO:0008352), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), growth cone (GO:0030426), midbody (GO:0030496), neuronal cell body (GO:0043025), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), axon (GO:0030424)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
microtubule cytoskeleton	3
supramolecular fiber organization	2
microtubule depolymerization	2
regulation of microtubule depolymerization	2
microtubule cytoskeleton organization	2
microtubule organizing center	2
intracellular membraneless organelle	2
establishment of protein localization	1
microtubule polymerization or depolymerization	1
protein depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
chromosome movement towards spindle pole	1
mitotic cell cycle process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
positive regulation of microtubule polymerization or depolymerization	1
positive regulation of protein depolymerization	1
positive regulation of supramolecular fiber organization	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cellular process	1
tubulin binding	1
protein dimerization activity	1
ATP hydrolysis activity	1
nucleoside-triphosphatase regulator activity	1
protein-containing complex binding	1
binding	1
spindle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1
cytoplasm	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KATNB1	KATNA1	O75449	987
KATNB1	LZTS2	Q9BRK4	892
KATNB1	KATNAL1	Q9BW62	758
KATNB1	TUBG1	P23258	726
KATNB1	TUBB2A	Q13885	688
KATNB1	TUBA1B	P04687	682
KATNB1	KATNAL2	Q8IYT4	643
KATNB1	TUBB	P05218	641
KATNB1	FIGN	Q5HY92	635
KATNB1	SPAST	Q9UBP0	609
KATNB1	KATNIP	O60303	605
KATNB1	KATNBL1	Q9H079	577
KATNB1	ASPM	Q8IZT6	555
KATNB1	CCNB1	P14635	495
KATNB1	TUBGCP2	Q9BSJ2	488

IntAct

60 interactions, top by confidence:

A	B	Type	Score
KATNB1	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
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
PFDN1	PFDN6	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
KATNB1	BTK	psi-mi:“MI:0915”(physical association)	0.590
ASPM	KATNB1	psi-mi:“MI:0403”(colocalization)	0.580
VHL	KATNB1	psi-mi:“MI:0915”(physical association)	0.560
KATNA1	CCT7	psi-mi:“MI:0914”(association)	0.530
PFDN2	CDC40	psi-mi:“MI:0914”(association)	0.530
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
KATNB1	KATNAL1	psi-mi:“MI:0915”(physical association)	0.500
KATNAL1	KATNB1	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (319): KATNB1 (Affinity Capture-MS), KATNB1 (Proximity Label-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Affinity Capture-MS), BTK (Affinity Capture-MS), KATNB1 (Proximity Label-MS), KATNB1 (Affinity Capture-MS), KATNB1 (Proximity Label-MS), KATNB1 (Two-hybrid)

ESM2 similar proteins: A0A396ISC0, O00423, O13286, O17468, O61585, O94423, P26309, P38328, P43254, P53197, P78972, P93471, Q04199, Q05BC3, Q09373, Q12834, Q16MY0, Q2TAF3, Q32SG6, Q3E906, Q4PSE4, Q4V7Y7, Q4V8C3, Q54MZ3, Q5H7C0, Q5ZIU8, Q62623, Q652L2, Q6DIP5, Q6NVM2, Q6S7B0, Q7K0L4, Q7ZUV2, Q7ZVL2, Q7ZX22, Q86Y33, Q8BG40, Q8CFJ9, Q8L3Z8, Q8LPL5

Diamond homologs: A0A1P8AW69, F4HTH8, F4KB17, O61585, Q4V7Y7, Q5ZIU8, Q6NVM2, Q7ZUV2, Q8BG40, Q8H0T9, Q9BVA0, Q13685, Q3SZK1, Q5RCG7, Q7YR70, Q5RAC9, Q676U5, Q9H079, Q9CWJ3, Q8VYZ5, Q94BQ3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
KATNB1	“up-regulates quantity by stabilization”	KATNA1	binding
KATNA1	“up-regulates activity”	KATNB1	binding
KATNAL2	“up-regulates activity”	KATNB1	binding
KATNB1	down-regulates	Microtubule_polimerization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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	7	88.9×	2e-10
Formation of tubulin folding intermediates by CCT/TriC	5	68.2×	9e-07
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	65.8×	9e-07
Chaperonin-mediated protein folding	5	48.5×	3e-06
Protein folding	5	41.9×	6e-06
Cilium Assembly	5	17.5×	3e-04
Organelle biogenesis and maintenance	5	10.7×	2e-03
Cell Cycle, Mitotic	5	7.8×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	7	16.4×	3e-05
microtubule cytoskeleton organization	5	13.8×	2e-03
protein stabilization	6	9.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	3
Uncertain significance	145
Likely benign	179
Benign	52

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1070302	NM_005886.3(KATNB1):c.888del (p.Ser297fs)	Pathogenic
180636	NM_005886.3(KATNB1):c.1604C>T (p.Ser535Leu)	Pathogenic
180637	NM_005886.3(KATNB1):c.1619T>G (p.Leu540Arg)	Pathogenic
180638	NM_005886.3(KATNB1):c.447del (p.Val150fs)	Pathogenic
180639	NM_005886.3(KATNB1):c.1A>G (p.Met1Val)	Pathogenic
180640	NM_005886.3(KATNB1):c.97G>T (p.Gly33Trp)	Pathogenic
180641	NM_005886.3(KATNB1):c.432+1G>A	Pathogenic
2344774	NM_005886.3(KATNB1):c.131_147del (p.Arg44fs)	Pathogenic
2704589	NM_005886.3(KATNB1):c.161del (p.Asn54fs)	Pathogenic
4818946	NM_005886.3(KATNB1):c.970C>T (p.Gln324Ter)	Pathogenic
1324607	NM_005886.3(KATNB1):c.1416+1G>A	Likely pathogenic
2636375	NM_005886.3(KATNB1):c.508_509delinsCATCTG (p.Thr170fs)	Likely pathogenic
3731466	NM_005886.3(KATNB1):c.1061C>G (p.Ser354Ter)	Likely pathogenic

SpliceAI

3369 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57741683:GTA:G	acceptor_loss	1.0000
16:57741684:TA:T	acceptor_loss	1.0000
16:57741685:A:AG	acceptor_gain	1.0000
16:57741685:AGA:A	acceptor_loss	1.0000
16:57741686:G:GA	acceptor_gain	1.0000
16:57741686:GAA:G	acceptor_gain	1.0000
16:57741686:GAAGA:G	acceptor_gain	1.0000
16:57744499:G:GT	donor_gain	1.0000
16:57744512:G:GG	donor_gain	1.0000
16:57750825:A:AG	acceptor_gain	1.0000
16:57750826:G:GA	acceptor_gain	1.0000
16:57750826:GTTC:G	acceptor_gain	1.0000
16:57750925:AAGG:A	donor_loss	1.0000
16:57751257:ACAG:A	acceptor_loss	1.0000
16:57751259:A:AG	acceptor_gain	1.0000
16:57751260:G:GT	acceptor_gain	1.0000
16:57751260:GCTCT:G	acceptor_gain	1.0000
16:57751301:GG:G	donor_gain	1.0000
16:57751302:GG:G	donor_gain	1.0000
16:57751302:GGTA:G	donor_loss	1.0000
16:57751637:TCAG:T	acceptor_loss	1.0000
16:57751639:A:AG	acceptor_gain	1.0000
16:57751639:A:C	acceptor_loss	1.0000
16:57751639:AG:A	acceptor_gain	1.0000
16:57751639:AGG:A	acceptor_gain	1.0000
16:57751639:AGGG:A	acceptor_gain	1.0000
16:57751640:G:A	acceptor_gain	1.0000
16:57751640:G:GG	acceptor_gain	1.0000
16:57751640:GGG:G	acceptor_gain	1.0000
16:57751640:GGGG:G	acceptor_gain	1.0000

AlphaMissense

4296 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57744490:T:A	W90R	1.000
16:57744490:T:C	W90R	1.000
16:57751264:T:A	W132R	1.000
16:57751264:T:C	W132R	1.000
16:57751943:T:A	W174R	1.000
16:57751943:T:C	W174R	1.000
16:57741762:G:A	G39D	0.999
16:57741765:G:A	G40E	0.999
16:57741788:T:A	W48R	0.999
16:57741788:T:C	W48R	0.999
16:57744463:G:C	G81R	0.999
16:57744464:G:A	G81D	0.999
16:57744476:G:A	G85D	0.999
16:57750899:C:A	A121D	0.999
16:57750901:T:C	S122P	0.999
16:57750902:C:A	S122Y	0.999
16:57750902:C:T	S122F	0.999
16:57750905:G:A	G123D	0.999
16:57750907:T:C	S124P	0.999
16:57750913:G:C	D126H	0.999
16:57750914:A:T	D126V	0.999
16:57751265:G:C	W132S	0.999
16:57751266:G:C	W132C	0.999
16:57751266:G:T	W132C	0.999
16:57751672:T:C	F155S	0.999
16:57751674:A:C	S156R	0.999
16:57751676:C:A	S156R	0.999
16:57751676:C:G	S156R	0.999
16:57751689:T:A	W161R	0.999
16:57751689:T:C	W161R	0.999

dbSNP variants (sampled 300 via entrez): RS1000217607 (16:57743990 G>A,T), RS1000280443 (16:57755598 G>A,C,T), RS1000449692 (16:57738897 G>A), RS1000709418 (16:57750104 A>C), RS1000815643 (16:57734586 C>T), RS1000843489 (16:57734904 G>C), RS1001186831 (16:57738537 T>A), RS1001203480 (16:57738444 C>T), RS1001258914 (16:57743897 C>A,G,T), RS1001309546 (16:57743408 G>C,T), RS1001340628 (16:57743719 C>T), RS1001557238 (16:57749416 G>C), RS1002062259 (16:57734552 G>A,C), RS1002239222 (16:57739702 G>A), RS1002347785 (16:57744809 C>G)

Disease associations

OMIM: gene MIM:602703 | disease phenotypes: MIM:616212

GenCC curated gene-disease

Disease	Classification	Inheritance
lissencephaly 6 with microcephaly	Definitive	Autosomal recessive
microlissencephaly	Supportive	Autosomal recessive

Mondo (3): lissencephaly 6 with microcephaly (MONDO:0014534), intellectual disability (MONDO:0001071), microlissencephaly (MONDO:0015204)

Orphanet (2): Microlissencephaly (Orphanet:1083), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000269	Prominent occiput
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000350	Small forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000479	Abnormal retinal morphology
HP:0000664	Synophrys
HP:0000687	Widely spaced teeth
HP:0000954	Single transverse palmar crease
HP:0001181	Adducted thumb
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001274	Agenesis of corpus callosum

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879844 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
Copper	affects binding, decreases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Chelating Agents	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Thiram	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3860480	Binding	Binding affinity to katanin p80 subunit in human NCI-H1975 cell lysate using biotin-labeled compound preincubated for 24 hrs followed by streptavidin-conjugated beads addition measured after 2 hrs by immunoblot analysis	Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders