KNOP1

Summary

KNOP1 (lysine rich nucleolar protein 1, HGNC:34404) is a protein-coding gene on chromosome 16p12.3, encoding Lysine-rich nucleolar protein 1 (Q1ED39).

The protein encoded by this gene is a nucleolar protein that interacts with zinc finger 106 protein. The encoded protein has several of the same characteristics as nucleostemin and may be involved in testis development.

Source: NCBI Gene 400506 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001012991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34404
Approved symbol	KNOP1
Name	lysine rich nucleolar protein 1
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	101F10.1, FAM191A, TSG118
Ensembl gene	ENSG00000103550
Ensembl biotype	protein_coding
OMIM	621293
Entrez	400506

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 retained_intron

ENST00000219837, ENST00000564480, ENST00000565844, ENST00000567367, ENST00000568230, ENST00000858467, ENST00000858468, ENST00000918604, ENST00000918605, ENST00000918606, ENST00000918607, ENST00000918608, ENST00000953641, ENST00000953642

RefSeq mRNA: 12 — MANE Select: NM_001012991 NM_001012991, NM_001348527, NM_001348528, NM_001348529, NM_001348530, NM_001348531, NM_001348532, NM_001348533, NM_001348534, NM_001348535, NM_001348536, NM_001348537

CCDS: CCDS42127

Canonical transcript exons

ENST00000219837 — 5 exons

Exon	Start	End
ENSE00000676004	19710509	19710586
ENSE00002602627	19701937	19707221
ENSE00002621503	19718158	19718227
ENSE00003581877	19711372	19711440
ENSE00003612772	19714118	19715037

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3317 / max 266.7659, expressed in 1672 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156578	8.0669	1630
156577	0.9076	596
156576	0.2043	85
156579	0.1529	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.33	gold quality
tendon of biceps brachii	UBERON:0008188	93.98	gold quality
medial globus pallidus	UBERON:0002477	90.85	gold quality
globus pallidus	UBERON:0001875	90.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.08	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.92	gold quality
calcaneal tendon	UBERON:0003701	88.91	gold quality
buccal mucosa cell	CL:0002336	88.64	gold quality
corpus callosum	UBERON:0002336	88.58	gold quality
lateral globus pallidus	UBERON:0002476	88.58	gold quality
tendon	UBERON:0000043	88.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.34	gold quality
cervix squamous epithelium	UBERON:0006922	88.29	silver quality
islet of Langerhans	UBERON:0000006	88.01	gold quality
vena cava	UBERON:0004087	87.98	silver quality
inferior olivary complex	UBERON:0002127	87.92	gold quality
inferior vagus X ganglion	UBERON:0005363	87.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.27	gold quality
substantia nigra pars compacta	UBERON:0001965	87.13	gold quality
oocyte	CL:0000023	87.05	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	86.78	gold quality
mucosa of transverse colon	UBERON:0004991	86.68	gold quality
putamen	UBERON:0001874	86.64	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.50	gold quality
ganglionic eminence	UBERON:0004023	86.48	gold quality
nipple	UBERON:0002030	86.36	gold quality
spinal cord	UBERON:0002240	86.30	gold quality
type B pancreatic cell	CL:0000169	86.25	gold quality
cranial nerve II	UBERON:0000941	86.18	gold quality
pylorus	UBERON:0001166	86.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting KNOP1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-92B-5P	99.36	63.29	110
HSA-MIR-7109-5P	99.18	66.13	1057

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	knop1	ENSDARG00000077721
mus_musculus	Knop1	ENSMUSG00000030980
rattus_norvegicus	Knop1	ENSRNOG00000070112

Protein

Protein identifiers

Lysine-rich nucleolar protein 1 — Q1ED39 (reviewed: Q1ED39)

Alternative names: Protein FAM191A, Testis-specific gene 118 protein

All UniProt accessions (4): Q1ED39, H3BMC9, H3BNU8, H3BPL4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with ZNF106.

Subcellular location. Nucleus. Nucleolus.

RefSeq proteins (12): NP_001013009, NP_001335456, NP_001335457, NP_001335458, NP_001335459, NP_001335460, NP_001335461, NP_001335462, NP_001335463, NP_001335464, NP_001335465, NP_001335466 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028124	SMAP_dom	Domain

Pfam: PF15477

UniProt features (37 total): cross-link 14, modified residue 8, compositionally biased region 7, region of interest 4, sequence variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q1ED39-F1	53.75	0.04

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 (22): 42, 50, 111, 132, 265, 308, 310, 430, 7, 101, 130, 249, 249, 275, 287, 305, 319, 353, 373, 375 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, ONKEN_UVEAL_MELANOMA_UP, WANG_LMO4_TARGETS_DN, SCHLOSSER_SERUM_RESPONSE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, chr16p12, SANSOM_APC_TARGETS_REQUIRE_MYC, GOCC_NUCLEOLUS, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_DN, BRUINS_UVC_RESPONSE_MIDDLE, LEE_BMP2_TARGETS_DN, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3

GO Biological Process (0):

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (2): nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KNOP1	IQCK	Q8N0W5	736
KNOP1	ZNF106	Q9H2Y7	643
KNOP1	DRG1	Q9Y295	533
KNOP1	KRTAP19-8	Q3LI54	517
KNOP1	WDR38	Q5JTN6	483
KNOP1	FAM133B	Q5BKY9	439
KNOP1	OR5L2	Q8NGL0	417
KNOP1	IGSF6	O95976	393
KNOP1	TCHH	Q07283	387
KNOP1	GDE1	Q9NZC3	384
KNOP1	OR5L1	Q8NGL2	371
KNOP1	ANKRD36B	Q8N2N9	357
KNOP1	TMEM186	Q96B77	349
KNOP1	INO80D	Q53TQ3	339
KNOP1	RPUSD1	Q9UJJ7	329

IntAct

155 interactions, top by confidence:

A	B	Type	Score
KNOP1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
RPS14	CCZ1B	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
KNOP1	AP2M1	psi-mi:“MI:0915”(physical association)	0.560
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
KNOP1	DHX15	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
PPAN	PPM1G	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
KNOP1	MAGEB2	psi-mi:“MI:0914”(association)	0.530
EXOSC4	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
PDGFRL	ANKRD28	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530

BioGRID (354): KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS), ZNF106 (Affinity Capture-MS), CENPN (Affinity Capture-MS), NMNAT1 (Affinity Capture-MS), SHQ1 (Affinity Capture-MS), KNOP1 (Affinity Capture-MS)

ESM2 similar proteins: A2A3V1, A2A995, A5D7J3, B1AX39, O15446, O60303, O88573, P0DPK0, P23497, Q14684, Q1ED39, Q2KIN0, Q3KRF1, Q3TFK5, Q3UY34, Q4R2Z8, Q566R3, Q58CQ0, Q5I034, Q5PQK4, Q5PQN4, Q5SU73, Q5XG69, Q66H19, Q66LM6, Q68A65, Q6IR42, Q6NTE8, Q6P1D7, Q6P9P0, Q76KJ5, Q7L190, Q80YR5, Q8BI29, Q8BVK9, Q8C0X0, Q8C753, Q8IY92, Q8IYF1, Q8K4R9

Diamond homologs: A5D7J3, Q0IIX4, Q1ED39, Q6DDU5, Q9Z2Q2, O00193, Q3MHL8, Q5RD18, Q90368, Q9I9J6, Q9R0P4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 164 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
Peptide chain elongation	23	27.8×	1e-25
Viral mRNA Translation	23	27.8×	1e-25
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	23	27.5×	1e-25
Selenocysteine synthesis	23	26.3×	3e-25
Eukaryotic Translation Termination	23	26.3×	3e-25
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	23	25.8×	4e-25
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	23	25.8×	4e-25
Response of EIF2AK4 (GCN2) to amino acid deficiency	24	25.3×	1e-25

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	24	30.2×	1e-26
ribosomal large subunit biogenesis	8	24.1×	1e-07
translation	23	16.1×	6e-19
ribosomal small subunit biogenesis	10	15.5×	1e-07
rRNA processing	13	12.5×	8e-09
negative regulation of translation	7	9.3×	1e-03
RNA processing	6	8.9×	3e-03
RNA splicing	10	6.0×	8e-04

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	60
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1418 predictions. Top by Δscore:

Variant	Effect	Δscore
16:19706917:T:TA	donor_gain	1.0000
16:19706930:A:AC	donor_gain	1.0000
16:19706931:C:CC	donor_gain	1.0000
16:19706942:T:A	donor_gain	1.0000
16:19707008:T:TA	donor_gain	1.0000
16:19707009:C:A	donor_gain	1.0000
16:19710502:AACTT:A	donor_loss	1.0000
16:19710503:ACTT:A	donor_loss	1.0000
16:19710504:CTT:C	donor_loss	1.0000
16:19710505:TTA:T	donor_loss	1.0000
16:19710506:TACC:T	donor_loss	1.0000
16:19710507:A:AC	donor_gain	1.0000
16:19710507:ACC:A	donor_loss	1.0000
16:19710507:ACCGT:A	donor_gain	1.0000
16:19710508:C:A	donor_loss	1.0000
16:19710508:C:CT	donor_gain	1.0000
16:19710508:CCGT:C	donor_gain	1.0000
16:19710508:CCGTC:C	donor_gain	1.0000
16:19710517:T:TA	donor_gain	1.0000
16:19710582:CTCAC:C	acceptor_gain	1.0000
16:19710583:TCAC:T	acceptor_gain	1.0000
16:19710583:TCACC:T	acceptor_gain	1.0000
16:19710584:CAC:C	acceptor_gain	1.0000
16:19710584:CACC:C	acceptor_gain	1.0000
16:19710585:AC:A	acceptor_gain	1.0000
16:19710585:ACC:A	acceptor_loss	1.0000
16:19710586:CC:C	acceptor_gain	1.0000
16:19710587:C:CC	acceptor_gain	1.0000
16:19710592:C:CT	acceptor_gain	1.0000
16:19710593:A:T	acceptor_gain	1.0000

AlphaMissense

3040 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:19707203:A:G	W362R	0.999
16:19707203:A:T	W362R	0.999
16:19707159:A:C	F376L	0.998
16:19707159:A:T	F376L	0.998
16:19707161:A:G	F376L	0.998
16:19707201:C:A	W362C	0.998
16:19707201:C:G	W362C	0.998
16:19707160:A:G	F376S	0.996
16:19710570:A:G	L335S	0.996
16:19710566:T:A	Q336H	0.995
16:19710566:T:G	Q336H	0.995
16:19710581:C:A	R331S	0.994
16:19710581:C:G	R331S	0.994
16:19707202:C:G	W362S	0.992
16:19707151:A:G	L379P	0.991
16:19710579:C:G	R332P	0.991
16:19710552:C:G	R341P	0.990
16:19707160:A:C	F376C	0.989
16:19710582:C:G	R331T	0.989
16:19707136:T:A	K384I	0.988
16:19707186:A:C	F367L	0.988
16:19707186:A:T	F367L	0.988
16:19707188:A:G	F367L	0.988
16:19710574:C:G	A334P	0.988
16:19707187:A:G	F367S	0.987
16:19711396:G:C	N321K	0.987
16:19711396:G:T	N321K	0.987
16:19706979:G:C	F436L	0.985
16:19706979:G:T	F436L	0.985
16:19706981:A:G	F436L	0.985

dbSNP variants (sampled 300 via entrez): RS1000101254 (16:19717218 T>A), RS1000438223 (16:19715517 T>G), RS1000472411 (16:19719912 A>C,G), RS1000521338 (16:19719713 C>A,G,T), RS1000546754 (16:19704491 T>G), RS1000764947 (16:19710148 C>T), RS1001111994 (16:19704350 G>T), RS1001205507 (16:19715123 T>A,C), RS1001259662 (16:19715241 C>T), RS1001564531 (16:19704156 C>A), RS1001616322 (16:19718022 G>A,C), RS1001811200 (16:19716422 G>A), RS1002282321 (16:19703759 T>C,G), RS1002381669 (16:19701761 C>A,T), RS1002402367 (16:19716658 G>A)

Disease associations

OMIM: gene MIM:621293 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Diuron	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Manganese	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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