NSL1

Summary

NSL1 (NSL1 component of MIS12 kinetochore complex, HGNC:24548) is a protein-coding gene on chromosome 1q32.3, encoding Kinetochore-associated protein NSL1 homolog (Q96IY1). Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. It is a common-essential gene (DepMap: required in 95.5% of cancer cell lines).

This gene encodes a protein with two coiled-coil domains that localizes to kinetochores, which are chromosome-associated structures that attach to microtubules and mediate chromosome movements during cell division. The encoded protein is part of a conserved protein complex that includes two chromodomain-containing proteins and a component of the outer plate of the kinetochore. This protein complex is proposed to bridge centromeric heterochromatin with the outer kinetochore structure. Multiple transcript variants encoding different isoforms have been found for this gene. There is a pseudogene of the 3’ UTR region of this gene on chromosome X.

Source: NCBI Gene 25936 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• Cancer dependency (DepMap): dependent in 95.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_015471

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24548
Approved symbol	NSL1
Name	NSL1 component of MIS12 kinetochore complex
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	DC8, DKFZP566O1646, MIS14
Ensembl gene	ENSG00000117697
Ensembl biotype	protein_coding
OMIM	609174
Entrez	25936

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000366976, ENST00000366977, ENST00000366978, ENST00000473995, ENST00000487995, ENST00000626725, ENST00000862262, ENST00000862263, ENST00000935315

RefSeq mRNA: 5 — MANE Select: NM_015471 NM_001042549, NM_001297736, NM_001297737, NM_001297739, NM_015471

CCDS: CCDS1509, CCDS53474, CCDS73025

Canonical transcript exons

ENST00000366977 — 6 exons

Exon	Start	End
ENSE00001003343	212782372	212782426
ENSE00001443161	212726153	212738686
ENSE00003498613	212739534	212739601
ENSE00003597806	212784363	212784493
ENSE00003637527	212787559	212787637
ENSE00003850078	212791530	212791777

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5228 / max 271.3708, expressed in 1780 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17427	15.3688	1780
17424	0.1541	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.60	gold quality
oocyte	CL:0000023	97.52	gold quality
cranial nerve II	UBERON:0000941	96.76	gold quality
germinal epithelium of ovary	UBERON:0001304	93.87	gold quality
choroid plexus epithelium	UBERON:0003911	93.71	gold quality
hair follicle	UBERON:0002073	93.60	gold quality
tibia	UBERON:0000979	93.07	gold quality
inferior vagus X ganglion	UBERON:0005363	92.95	gold quality
trabecular bone tissue	UBERON:0002483	92.93	gold quality
nephron tubule	UBERON:0001231	92.76	gold quality
parietal pleura	UBERON:0002400	92.53	gold quality
mammary duct	UBERON:0001765	92.40	gold quality
superficial temporal artery	UBERON:0001614	92.19	gold quality
pleura	UBERON:0000977	92.13	gold quality
corpus callosum	UBERON:0002336	92.10	gold quality
palpebral conjunctiva	UBERON:0001812	92.00	gold quality
epithelium of mammary gland	UBERON:0003244	91.96	gold quality
visceral pleura	UBERON:0002401	91.88	gold quality
pigmented layer of retina	UBERON:0001782	91.36	gold quality
cauda epididymis	UBERON:0004360	91.30	gold quality
epithelium of nasopharynx	UBERON:0001951	91.19	gold quality
caput epididymis	UBERON:0004358	91.06	gold quality
endothelial cell	CL:0000115	90.86	gold quality
monocyte	CL:0000576	90.83	gold quality
jejunal mucosa	UBERON:0000399	90.82	gold quality
mononuclear cell	CL:0000842	90.78	gold quality
corpus epididymis	UBERON:0004359	90.75	gold quality
subthalamic nucleus	UBERON:0001906	90.73	gold quality
renal glomerulus	UBERON:0000074	90.66	gold quality
leukocyte	CL:0000738	90.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.88
E-HCAD-31	no	2.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

425 targeting NSL1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• The hMis14, which contains a tripartite-binding domain for HP1 and two other kinetochore proteins, hMis13 and blinkin, is a cornerstone for the assembly of the inner centromere and kinetochore. (PMID:20231385)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nsl1	ENSDARG00000024471
mus_musculus	Nsl1	ENSMUSG00000062510
rattus_norvegicus	Nsl1	ENSRNOG00000042286

Protein

Protein identifiers

Kinetochore-associated protein NSL1 homolog — Q96IY1 (reviewed: Q96IY1)

All UniProt accessions (4): Q96IY1, Q53FM2, Q5SY74, Q5SY76

UniProt curated annotations — full annotation on UniProt →

Function. Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis.

Subunit / interactions. Component of the MIS12 complex composed of MIS12, DSN1, NSL1/DC8 and PMF1. Interacts with KNL1.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IY1-1	1	yes
Q96IY1-2	2

RefSeq proteins (5): NP_001036014, NP_001284665, NP_001284666, NP_001284668, NP_056286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013950	Mis14/Nsl1	Family

Pfam: PF08641

UniProt features (17 total): helix 6, turn 3, modified residue 2, strand 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5LSI	X-RAY DIFFRACTION	2
4NF9	X-RAY DIFFRACTION	2.8
8PPR	ELECTRON MICROSCOPY	3
5LSJ	X-RAY DIFFRACTION	3.25
5LSK	X-RAY DIFFRACTION	3.5
8Q5H	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IY1-F1	76.37	0.47

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 (2): 4, 244

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 228 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_CHROMOSOME_LOCALIZATION, GOZGIT_ESR1_TARGETS_DN, MORF_ATRX, PUJANA_CHEK2_PCC_NETWORK, GOBP_ORGANELLE_FISSION, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_HIF1A_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_MITOTIC_CELL_CYCLE, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_ORGANELLE_LOCALIZATION, CUI_TCF21_TARGETS_2_UP

GO Biological Process (4): mitotic sister chromatid segregation (GO:0000070), attachment of spindle microtubules to kinetochore (GO:0008608), cell division (GO:0051301), chromosome segregation (GO:0007059)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): MIS12/MIND type complex (GO:0000444), kinetochore (GO:0000776), spindle pole (GO:0000922), outer kinetochore (GO:0000940), nucleus (GO:0005634), cytosol (GO:0005829), nuclear speck (GO:0016607), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle process	2
intracellular membraneless organelle	2
cellular anatomical structure	2
sister chromatid segregation	1
mitotic nuclear division	1
mitotic cell cycle process	1
microtubule binding	1
metaphase chromosome alignment	1
cellular process	1
binding	1
outer kinetochore	1
condensed chromosome, centromeric region	1
supramolecular complex	1
spindle	1
kinetochore	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
chromosomal region	1

Protein interactions and networks

STRING

1078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NSL1	DSN1	Q9H410	987
NSL1	A0A087WT04	A0A087WT04	949
NSL1	PMF1	Q6P1K2	949
NSL1	ZWINT	O95229	935
NSL1	PROCR	Q9UNN8	922
NSL1	CMC2	Q9NRP2	875
NSL1	ICAM1	P05362	834
NSL1	KNL1	Q8NG31	827
NSL1	CBX5	P45973	810
NSL1	AWAT2	Q6E213	727
NSL1	SECISBP2L	Q93073	680
NSL1	ZW10	O43264	657
NSL1	NXT2	Q9NPJ8	643
NSL1	SCARB2	Q14108	637
NSL1	CD36	P16671	637

IntAct

92 interactions, top by confidence:

A	B	Type	Score
NUF2	NDC80	psi-mi:“MI:0914”(association)	0.950
SPC25	NDC80	psi-mi:“MI:0914”(association)	0.940
ZWINT	NDC80	psi-mi:“MI:0914”(association)	0.940
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
DSN1	NSL1	psi-mi:“MI:2364”(proximity)	0.920
NSL1	DSN1	psi-mi:“MI:2364”(proximity)	0.920
NSL1	DSN1	psi-mi:“MI:0915”(physical association)	0.920
DSN1	NSL1	psi-mi:“MI:0915”(physical association)	0.920
DSN1	ZWINT	psi-mi:“MI:0914”(association)	0.900
MIS12	ZWINT	psi-mi:“MI:0914”(association)	0.900
MIS12	NSL1	psi-mi:“MI:2364”(proximity)	0.890

BioGRID (159): ANXA1 (Affinity Capture-MS), CASC5 (Affinity Capture-MS), ZWINT (Affinity Capture-MS), DSN1 (Affinity Capture-MS), SPC24 (Affinity Capture-MS), NDC80 (Affinity Capture-MS), BRCA2 (Affinity Capture-MS), PMF1 (Affinity Capture-MS), CRNN (Affinity Capture-MS), MIS12 (Affinity Capture-MS), NUF2 (Affinity Capture-MS), SPC25 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), SPRR3 (Affinity Capture-MS), PMF1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTD5, A0A1B0GUX0, A0A3Q1MT14, A4D263, A6NL82, A6QQL5, A8QW39, B0UXH9, B5X5D0, B9EJX3, E1B9R1, F1MMV1, Q148A4, Q1JPL0, Q2T9T0, Q32KQ1, Q32L72, Q32L77, Q32P67, Q3V0J4, Q5BN46, Q5NC57, Q5NC83, Q5SPV6, Q5SS90, Q5SVJ3, Q5VTT2, Q5VZQ5, Q66HC0, Q66HR9, Q6AYM0, Q6NXP0, Q6P3G4, Q6ZVS7, Q80X60, Q8CDT5, Q8CDU5, Q8N5S3, Q8N7U6, Q8N865

Diamond homologs: Q8K305, Q96IY1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NSL1	“form complex”	“MIS12 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	11	32.0×	6e-12
Amplification of signal from the kinetochores	6	29.5×	2e-06
EML4 and NUDC in mitotic spindle formation	11	25.5×	4e-11
Resolution of Sister Chromatid Cohesion	11	23.8×	6e-11
Mitotic Spindle Checkpoint	6	23.8×	5e-06
RHO GTPases Activate Formins	11	21.4×	1e-10
Mitotic Prometaphase	11	19.0×	4e-10
Cell Cycle Checkpoints	8	17.7×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
attachment of spindle microtubules to kinetochore	8	162.8×	4e-14
mitotic spindle assembly checkpoint signaling	6	73.3×	3e-08
mitotic sister chromatid segregation	5	52.3×	4e-06
chromosome segregation	7	26.4×	1e-06
cell division	12	12.0×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212784357:TCTTA:T	donor_loss	1.0000
1:212784358:CTTA:C	donor_loss	1.0000
1:212784359:TTACC:T	donor_loss	1.0000
1:212784360:TACCA:T	donor_loss	1.0000
1:212784361:A:AC	donor_gain	1.0000
1:212784361:A:T	donor_loss	1.0000
1:212784362:C:CC	donor_gain	1.0000
1:212784362:CCAGA:C	donor_gain	1.0000
1:212784489:AGAAT:A	acceptor_gain	1.0000
1:212784490:GAAT:G	acceptor_gain	1.0000
1:212784491:AAT:A	acceptor_gain	1.0000
1:212784492:AT:A	acceptor_gain	1.0000
1:212784493:TC:T	acceptor_loss	1.0000
1:212784494:C:CC	acceptor_gain	1.0000
1:212784494:C:T	acceptor_loss	1.0000
1:212784495:T:A	acceptor_loss	1.0000
1:212784497:T:TC	acceptor_gain	1.0000
1:212784498:T:C	acceptor_gain	1.0000
1:212784498:T:TC	acceptor_gain	1.0000
1:212787553:ACAT:A	donor_loss	1.0000
1:212787554:CATA:C	donor_loss	1.0000
1:212787555:ATACC:A	donor_loss	1.0000
1:212787556:TACC:T	donor_loss	1.0000
1:212787557:A:AC	donor_gain	1.0000
1:212787557:AC:A	donor_gain	1.0000
1:212787558:C:CC	donor_gain	1.0000
1:212787558:C:CT	donor_loss	1.0000
1:212787558:CC:C	donor_gain	1.0000
1:212787582:T:TA	donor_gain	1.0000
1:212787637:TCTG:T	acceptor_loss	1.0000

AlphaMissense

1858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212784431:G:T	R126S	0.980
1:212784430:C:G	R126P	0.979
1:212787611:A:C	N87K	0.979
1:212787611:A:T	N87K	0.979
1:212787589:A:G	W95R	0.978
1:212787589:A:T	W95R	0.978
1:212787625:C:G	A83P	0.974
1:212784451:A:T	I119K	0.969
1:212791646:A:G	C40R	0.969
1:212787621:A:T	V84E	0.963
1:212787587:C:A	W95C	0.959
1:212787587:C:G	W95C	0.959
1:212787624:G:T	A83D	0.951
1:212738652:A:G	F201S	0.949
1:212784460:T:A	D116V	0.949
1:212787632:A:C	F80L	0.949
1:212787632:A:T	F80L	0.949
1:212787634:A:G	F80L	0.949
1:212784432:T:A	K125N	0.948
1:212784432:T:G	K125N	0.948
1:212787633:A:G	F80S	0.947
1:212738640:A:G	L205P	0.942
1:212784451:A:C	I119R	0.941
1:212787605:G:C	S89R	0.941
1:212787605:G:T	S89R	0.941
1:212787607:T:G	S89R	0.941
1:212791635:C:A	K43N	0.938
1:212791635:C:G	K43N	0.938
1:212784381:T:A	K142N	0.934
1:212784381:T:G	K142N	0.934

dbSNP variants (sampled 300 via entrez): RS1000022133 (1:212752324 T>C), RS1000023862 (1:212790040 G>C), RS1000029011 (1:212785415 T>C,G), RS1000056461 (1:212789674 T>C), RS1000081255 (1:212744586 T>C,G), RS1000256246 (1:212782564 G>A), RS1000263609 (1:212775808 T>C), RS1000290047 (1:212738942 T>C), RS1000308681 (1:212731778 G>C,T), RS1000311083 (1:212737490 A>T), RS1000370042 (1:212775614 A>C), RS1000431749 (1:212744973 T>C), RS1000444982 (1:212775305 C>A,G,T), RS1000449243 (1:212782093 T>C,G), RS1000491623 (1:212730424 G>A,C)

Disease associations

OMIM: gene MIM:609174 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Ethanol	increases abundance, affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Piroxicam	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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