IQUB

Summary

IQUB (IQ motif and ubiquitin domain containing, HGNC:21995) is a protein-coding gene on chromosome 7q31.32, encoding IQ motif and ubiquitin-like domain-containing protein (Q8NA54). Adapter protein that anchors the radial spoke 1 (RS1) complex to the A microtubule of outer doublet microtubules in axonemes.

Involved in flagellated sperm motility and mating. Predicted to be located in sperm flagellum. Predicted to be part of radial spoke. Predicted to be active in acrosomal vesicle and motile cilium.

Source: NCBI Gene 154865 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 122 total
• MANE Select transcript: NM_178827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21995
Approved symbol	IQUB
Name	IQ motif and ubiquitin domain containing
Location	7q31.32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35834
Ensembl gene	ENSG00000164675
Ensembl biotype	protein_coding
OMIM	620557
Entrez	154865

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000324698, ENST00000466202, ENST00000469057, ENST00000483567, ENST00000484508, ENST00000488987, ENST00000889595, ENST00000918247

RefSeq mRNA: 3 — MANE Select: NM_178827 NM_001282855, NM_001321293, NM_178827

CCDS: CCDS5787

Canonical transcript exons

ENST00000324698 — 13 exons

Exon	Start	End
ENSE00001086531	123479795	123479970
ENSE00001086534	123496696	123496906
ENSE00001286118	123503202	123503363
ENSE00001286128	123534492	123534595
ENSE00001922373	123452193	123452925
ENSE00003574388	123457381	123457566
ENSE00003588098	123469214	123469384
ENSE00003596879	123509901	123510035
ENSE00003603918	123502597	123502752
ENSE00003615535	123464833	123465009
ENSE00003657786	123511944	123512344
ENSE00003668542	123461357	123461605
ENSE00003679495	123502944	123503116

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 98.17.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0315 / max 73.4863, expressed in 360 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85963	1.0315	360

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.17	gold quality
secondary oocyte	CL:0000655	90.40	gold quality
oocyte	CL:0000023	88.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.90	gold quality
buccal mucosa cell	CL:0002336	87.68	gold quality
bronchial epithelial cell	CL:0002328	87.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.99	gold quality
left testis	UBERON:0004533	85.79	gold quality
bronchus	UBERON:0002185	85.28	gold quality
testis	UBERON:0000473	84.99	gold quality
right testis	UBERON:0004534	84.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.58	gold quality
right uterine tube	UBERON:0001302	79.50	gold quality
oviduct epithelium	UBERON:0004804	77.20	gold quality
adult organism	UBERON:0007023	70.46	gold quality
epithelium of nasopharynx	UBERON:0001951	69.78	gold quality
fallopian tube	UBERON:0003889	69.15	gold quality
metanephros cortex	UBERON:0010533	65.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	65.37	gold quality
lower esophagus	UBERON:0013473	65.25	gold quality
left lobe of thyroid gland	UBERON:0001120	63.80	gold quality
thyroid gland	UBERON:0002046	63.60	gold quality
adrenal tissue	UBERON:0018303	62.81	gold quality
right lobe of thyroid gland	UBERON:0001119	62.64	gold quality
islet of Langerhans	UBERON:0000006	61.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.81	gold quality
gall bladder	UBERON:0002110	61.49	gold quality
adult mammalian kidney	UBERON:0000082	61.11	gold quality
nasal cavity mucosa	UBERON:0001826	61.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.64
E-MTAB-9388	yes	6.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting IQUB, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055

Literature-anchored findings (GeneRIF, showing 2)

• these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3beta/beta-catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer (PMID:29968965)
• IQUB deficiency causes male infertility by affecting the activity of p-ERK1/2/RSPH3. (PMID:36355624)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	iqub	ENSDARG00000061899
mus_musculus	Iqub	ENSMUSG00000046192
rattus_norvegicus	Iqub	ENSRNOG00000021729
drosophila_melanogaster	CG13855	FBGN0038960

Protein

Protein identifiers

IQ motif and ubiquitin-like domain-containing protein — Q8NA54 (reviewed: Q8NA54)

All UniProt accessions (2): A1A4Z1, Q8NA54

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that anchors the radial spoke 1 (RS1) complex to the A microtubule of outer doublet microtubules in axonemes. The triple radial spokes (RS1, RS2 and RS3) are required to modulate beating of the sperm flagellum. May play a role in inhibiting signaling via MAPK1/ERK2 and MAPK3/ERK1. Additionally, may play a role in the functioning of cilia. Not required for the functioning of tracheal or ependymal cilia.

Subunit / interactions. Component of the axonemal radial spoke 1 (RS1) complex, at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB. Does not appear to be part of radial spoke complexes 2 or 3 (RS2 or RS3). Interacts with CALM1. Interacts with DNAJB13. Interacts with DYNLL2. Interacts with NME5. Interacts with RSPH3. Interacts with RSPH9. Interacts with ZMYND10. Interacts with calmodulin; the interaction occurs in conditions of low but not high calcium.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme. Cell projection. Cilium.

Disease relevance. Defects in IQUB may be the cause of spermatogenic failure with radial spoke defects, leading to asthenospermia and male infertility. Sperm appear largely normal morphologically but with radial spoke defects, and their motility is severely reduced.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NA54-1	1	yes
Q8NA54-2	2

RefSeq proteins (3): NP_001269784, NP_001308222, NP_849149* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR037695	IQUB	Family
IPR057887	IQUB_helical	Domain

Pfam: PF00240, PF25805

UniProt features (25 total): strand 6, sequence variant 5, sequence conflict 3, turn 3, domain 2, helix 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1
2DAF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NA54-F1	75.60	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOCC_SECRETORY_GRANULE, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, LYF1_01, RYTTCCTG_ETS2_B, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_CELL_PROJECTION_ORGANIZATION, GOCC_CYTOPLASMIC_REGION, GOCC_SECRETORY_VESICLE, GOCC_MOTILE_CILIUM, GOCC_ACROSOMAL_VESICLE, GOCC_CILIUM

GO Biological Process (5): smoothened signaling pathway (GO:0007224), mating (GO:0007618), flagellated sperm motility (GO:0030317), cilium assembly (GO:0060271), cell projection organization (GO:0030030)

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

GO Cellular Component (9): radial spoke (GO:0001534), acrosomal vesicle (GO:0001669), motile cilium (GO:0031514), sperm flagellum (GO:0036126), 9+2 motile cilium (GO:0097729), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell surface receptor signaling pathway	1
sexual reproduction	1
multi-organism reproductive process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cellular component organization	1
binding	1
axoneme	1
protein-containing complex	1
secretory granule	1
cilium	1
9+2 motile cilium	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1411 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQUB	CFAP96	A7E2U8	607
IQUB	CFAP184	Q2M329	573
IQUB	CLXN	Q9HAE3	560
IQUB	DRC10	Q96DY2	556
IQUB	PIERCE1	Q5BN46	544
IQUB	ODAD2	Q5T2S8	539
IQUB	TTLL1	O95922	512
IQUB	ARMC3	Q5W041	507
IQUB	AARD	Q4LEZ3	505
IQUB	TMEM79	Q9BSE2	492
IQUB	ASB15	Q8WXK1	492
IQUB	DNALI1	O14645	465
IQUB	CFAP90	A4QMS7	465
IQUB	LRRC72	A6NJI9	452
IQUB	SYT16	Q17RD7	447

IntAct

250 interactions, top by confidence:

A	B	Type	Score
TRIM23	IQUB	psi-mi:“MI:0915”(physical association)	0.780
IQUB	TRIM23	psi-mi:“MI:0915”(physical association)	0.780
IQUB	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.720
BLZF1	IQUB	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-4	IQUB	psi-mi:“MI:0915”(physical association)	0.720
IQUB	BLZF1	psi-mi:“MI:0915”(physical association)	0.720
SMN1	IQUB	psi-mi:“MI:0915”(physical association)	0.720
IQUB	SMN1	psi-mi:“MI:0915”(physical association)	0.720
IQUB	IHO1	psi-mi:“MI:0915”(physical association)	0.670
IQUB	TRIM54	psi-mi:“MI:0915”(physical association)	0.670
IHO1	IQUB	psi-mi:“MI:0915”(physical association)	0.670
TRIM54	IQUB	psi-mi:“MI:0915”(physical association)	0.670
DYNLL1	IQUB	psi-mi:“MI:0915”(physical association)	0.560
TRIM42	IQUB	psi-mi:“MI:0915”(physical association)	0.560
IQUB		psi-mi:“MI:0915”(physical association)	0.560
TRIM27	IQUB	psi-mi:“MI:0915”(physical association)	0.560
IQUB	MAGEA6	psi-mi:“MI:0915”(physical association)	0.560
IQUB	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
IQUB	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (86): IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), IQUB (Two-hybrid), TRIM42 (Two-hybrid), CCDC36 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid)

ESM2 similar proteins: A0A1B0GW35, A6QNM3, B0R034, B1ANS9, B9EK06, D2KC46, D3ZY60, F1MS15, F1P065, F1REV3, O00522, O15091, O75747, P10911, P58069, Q008S8, Q14449, Q14D04, Q15283, Q32NR9, Q45GW3, Q4R366, Q4R6T7, Q5H9U9, Q5K651, Q5PQS3, Q5XGX5, Q5XIZ9, Q5ZLD2, Q60862, Q63713, Q69Z37, Q6DCF6, Q6S5J6, Q6TNJ1, Q75PQ8, Q80W71, Q86VD1, Q86YR7, Q8C5W4

Diamond homologs: Q45GW3, Q4R6T7, Q8CDK3, Q8NA54

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
Keratinization	8	9.5×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	5	17.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	110
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2219 predictions. Top by Δscore:

Variant	Effect	Δscore
7:123457376:CTTAC:C	donor_loss	1.0000
7:123457377:TTAC:T	donor_loss	1.0000
7:123457378:TAC:T	donor_loss	1.0000
7:123457379:A:AC	donor_gain	1.0000
7:123457380:C:CC	donor_gain	1.0000
7:123457380:C:T	donor_loss	1.0000
7:123457380:CCT:C	donor_gain	1.0000
7:123457571:A:C	acceptor_gain	1.0000
7:123457575:C:CT	acceptor_gain	1.0000
7:123469386:T:C	acceptor_gain	1.0000
7:123479971:C:CC	acceptor_gain	1.0000
7:123496695:CATT:C	donor_gain	1.0000
7:123511926:ATCTT:A	donor_gain	1.0000
7:123511930:T:TA	donor_gain	1.0000
7:123512340:TTTTC:T	acceptor_gain	1.0000
7:123512350:T:TC	acceptor_gain	1.0000
7:123531095:CAAAT:C	acceptor_gain	1.0000
7:123531099:T:C	acceptor_gain	1.0000
7:123531099:T:TC	acceptor_gain	1.0000
7:123457562:TGTAG:T	acceptor_gain	0.9900
7:123457564:TAG:T	acceptor_gain	0.9900
7:123457565:AG:A	acceptor_gain	0.9900
7:123457567:C:CA	acceptor_loss	0.9900
7:123457567:C:CC	acceptor_gain	0.9900
7:123457570:CA:C	acceptor_gain	0.9900
7:123457571:A:AC	acceptor_gain	0.9900
7:123457576:A:T	acceptor_gain	0.9900
7:123457580:CAAGT:C	acceptor_gain	0.9900
7:123457581:A:T	acceptor_gain	0.9900
7:123457586:T:C	acceptor_gain	0.9900

AlphaMissense

5247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:123464951:A:G	L547P	0.999
7:123469230:A:G	L522P	0.998
7:123457455:A:G	W707R	0.997
7:123457455:A:T	W707R	0.997
7:123469302:A:G	L498P	0.997
7:123469239:A:G	L519P	0.996
7:123469226:T:A	K523N	0.995
7:123469226:T:G	K523N	0.995
7:123457473:A:G	W701R	0.994
7:123457473:A:T	W701R	0.994
7:123457533:A:G	W681R	0.994
7:123457533:A:T	W681R	0.994
7:123469250:C:A	R515S	0.994
7:123469250:C:G	R515S	0.994
7:123457474:T:A	R700S	0.993
7:123457474:T:G	R700S	0.993
7:123457475:C:G	R700T	0.993
7:123464902:T:A	R563S	0.993
7:123464902:T:G	R563S	0.993
7:123469236:A:G	L520S	0.992
7:123469248:A:G	L516P	0.992
7:123457475:C:A	R700I	0.991
7:123464960:T:A	E544V	0.991
7:123469230:A:T	L522H	0.991
7:123503043:G:C	F256L	0.991
7:123503043:G:T	F256L	0.991
7:123503045:A:G	F256L	0.991
7:123457441:G:C	N711K	0.990
7:123457441:G:T	N711K	0.990
7:123457452:A:G	S708P	0.990

dbSNP variants (sampled 300 via entrez): RS1000037261 (7:123462019 GTTTAA>G), RS1000060310 (7:123481940 T>C), RS1000063963 (7:123533723 G>T), RS1000076885 (7:123465667 C>T), RS1000083618 (7:123465483 ATTTGTTAAACTG>A), RS1000108487 (7:123472183 C>T), RS1000207245 (7:123453251 G>A,T), RS1000209390 (7:123502192 T>C), RS1000237342 (7:123452462 A>AATT), RS1000304785 (7:123534006 T>C), RS1000359282 (7:123491753 T>C), RS1000406061 (7:123487246 A>T), RS1000419488 (7:123499651 C>T), RS1000462562 (7:123452284 T>A,C), RS1000580540 (7:123453628 T>G)

Disease associations

OMIM: gene MIM:620557 | 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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	2
methyleugenol	decreases expression	1
bisphenol A	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Amosite	increases methylation	1

Clinical trials (associated diseases)

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