IQCN

Summary

IQCN (IQ motif containing N, HGNC:29350) is a protein-coding gene on chromosome 19p13.11, encoding IQ domain-containing protein N (Q9H0B3). Essential for spermiogenesis and fertilization.

Involved in spermatid development. Located in mitochondrion. Implicated in spermatogenic failure 78.

Source: NCBI Gene 80726 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 327 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_001145304

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29350
Approved symbol	IQCN
Name	IQ motif containing N
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000130518
Ensembl biotype	protein_coding
OMIM	620160
Entrez	80726

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000392413, ENST00000593659, ENST00000595654, ENST00000599528, ENST00000599638, ENST00000600328, ENST00000600359, ENST00000608950, ENST00000865016

RefSeq mRNA: 3 — MANE Select: NM_001145304 NM_001145304, NM_001145305, NM_025249

CCDS: CCDS32958, CCDS46017, CCDS46018

Canonical transcript exons

ENST00000392413 — 4 exons

Exon	Start	End
ENSE00001399711	18264363	18267526
ENSE00003044345	18257098	18258106
ENSE00003465558	18269466	18269587
ENSE00003842467	18274403	18274452

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 89.70.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3570 / max 113.1475, expressed in 496 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179952	1.2733	487
179954	0.0537	6
179953	0.0239	4
179951	0.0061	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	89.70	gold quality
left testis	UBERON:0004533	88.33	gold quality
right testis	UBERON:0004534	88.30	gold quality
testis	UBERON:0000473	85.80	gold quality
right uterine tube	UBERON:0001302	85.10	gold quality
left uterine tube	UBERON:0001303	81.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.63	gold quality
mucosa of stomach	UBERON:0001199	79.86	gold quality
bone marrow cell	CL:0002092	79.09	gold quality
right ovary	UBERON:0002118	78.49	gold quality
left ovary	UBERON:0002119	78.40	gold quality
left lobe of thyroid gland	UBERON:0001120	77.41	gold quality
body of uterus	UBERON:0009853	77.41	gold quality
thyroid gland	UBERON:0002046	77.04	gold quality
tibial nerve	UBERON:0001323	76.79	gold quality
pituitary gland	UBERON:0000007	76.65	gold quality
right lobe of thyroid gland	UBERON:0001119	76.64	gold quality
granulocyte	CL:0000094	76.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.98	gold quality
endocervix	UBERON:0000458	75.32	gold quality
adenohypophysis	UBERON:0002196	75.20	gold quality
skin of leg	UBERON:0001511	74.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.40	gold quality
ovary	UBERON:0000992	73.53	gold quality
cerebellar hemisphere	UBERON:0002245	73.50	gold quality
skin of abdomen	UBERON:0001416	73.46	gold quality
cerebellar cortex	UBERON:0002129	73.39	gold quality
popliteal artery	UBERON:0002250	73.10	gold quality
tibial artery	UBERON:0007610	73.09	gold quality
spleen	UBERON:0002106	72.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.61

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Biallelic variants in IQCN cause sperm flagellar assembly defects and male infertility. (PMID:37140151)
• Loss-of-function mutations in IQCN cause male infertility in humans and mice owing to total fertilization failure. (PMID:37184908)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Iqcn	ENSMUSG00000110622
rattus_norvegicus	Iqcn	ENSRNOG00000068146

Paralogs (1): IQCE (ENSG00000106012)

Protein

Protein identifiers

IQ domain-containing protein N — Q9H0B3 (reviewed: Q9H0B3)

All UniProt accessions (5): Q9H0B3, A0A0G2JLK5, U3KQG6, U3KQN7, V9GY12

UniProt curated annotations — full annotation on UniProt →

Function. Essential for spermiogenesis and fertilization. May be required for manchette assembly in elongating spermatids.

Subunit / interactions. Interacts with calmodulin.

Disease relevance. Spermatogenic failure 78 (SPGF78) [MIM:620170] An autosomal recessive, male infertility disorder characterized by a high proportion of sperm head anomalies, primarily tapered and microcephalic heads, and an abnormal acrosome structure. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9H0B3-1	1	yes
Q9H0B3-2	2
Q9H0B3-3	3
Q9H0B3-4	4
Q9H0B3-5	5

RefSeq proteins (3): NP_001138776, NP_001138777, NP_079525 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR052318	CellDiv_DevSignal_Domain	Family

Pfam: PF00612

UniProt features (32 total): sequence variant 14, domain 6, splice variant 6, region of interest 4, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0B3-F1	46.56	0.13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, chr19p13, MODULE_49, CTR9_TARGET_GENES, IGLV5_37_TARGET_GENES, MIER1_TARGET_GENES, UBN1_TARGET_GENES, ZNF165_TARGET_GENES, ZNF175_TARGET_GENES, ZNF184_TARGET_GENES, ZNF223_TARGET_GENES, ZNF350_TARGET_GENES, ZNF563_TARGET_GENES

GO Biological Process (1): spermatid development (GO:0007286)

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

GO Cellular Component (2): nucleus (GO:0005634), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
germ cell development	1
spermatid differentiation	1
binding	1
cytoplasm	1

Protein interactions and networks

STRING

1002 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQCN	C2orf81	A6NN90	606
IQCN	CCDC154	A6NI56	586
IQCN	STMP1	E0CX11	572
IQCN	CFAP184	Q2M329	505
IQCN	GOLGA6L7	A0A1B0GV03	480
IQCN	C20orf173	Q96LM9	471
IQCN	JAKMIP3	Q5VZ66	470
IQCN	HEATR9	A2RTY3	461
IQCN	CABS1	Q96KC9	445
IQCN	TMCO5A	Q8N6Q1	437
IQCN	OR5J2	Q8NH18	418
IQCN	SPATA20	Q8TB22	403
IQCN	MYO3B	Q8WXR4	402
IQCN	LHFPL7	Q6ICI0	401
IQCN	SPATA31G1	Q5VYM1	400

IntAct

38 interactions, top by confidence:

A	B	Type	Score
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
CALML3	IQCN	psi-mi:“MI:0915”(physical association)	0.670
IQCN	CALM1	psi-mi:“MI:0915”(physical association)	0.670
LZTS2	IQCN	psi-mi:“MI:0915”(physical association)	0.670
IQCN	CALML3	psi-mi:“MI:0915”(physical association)	0.670
CALM1	IQCN	psi-mi:“MI:0915”(physical association)	0.670
IQCN	LZTS2	psi-mi:“MI:0915”(physical association)	0.670
HEL-S-72	IQCN	psi-mi:“MI:0915”(physical association)	0.560
RBM17	IQCN	psi-mi:“MI:0915”(physical association)	0.560
IQCN	HEL-S-72	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	IQCN	psi-mi:“MI:0915”(physical association)	0.560
IQCN	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
IQCN	PUF60	psi-mi:“MI:0915”(physical association)	0.560
IQCN	MID2	psi-mi:“MI:0915”(physical association)	0.560
IQCN	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
SIAH1	IQCN	psi-mi:“MI:0915”(physical association)	0.560
PUF60	IQCN	psi-mi:“MI:0915”(physical association)	0.560
MID2	IQCN	psi-mi:“MI:0915”(physical association)	0.560
IQCN	RBM17	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (119): KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), LZTS2 (Two-hybrid), RBM17 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid), KIAA1683 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTH6, A0A1B0GUW6, A0A1D5RMD1, A2AQH4, A4FU49, A6NJ88, C4P6S0, D3YU32, E9PAV3, F1QU13, I3L273, J3KML8, P70670, Q32L62, Q3V0E1, Q3V3Q4, Q4R729, Q5H9F3, Q5QJ38, Q5SWP3, Q5U4C1, Q5VWK0, Q5VYM1, Q68DN1, Q6AZ54, Q7TSG5, Q810T2, Q8CH19, Q8K4E0, Q8N3K9, Q8N5Q1, Q8NDH2, Q8TCU4, Q8WNU4, Q8WWL7, Q920R4, Q921B4, Q923B3, Q96JA4, Q96M34

Diamond homologs: A0A1D5RMD1, Q8WNU4, Q9H0B3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	249
Likely benign	54
Benign	0

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
3774324	IQCN, THR1305SER	Pathogenic
3774325	IQCN, SER1003PHE	Pathogenic
3774326	IQCN, R1125HIS	Pathogenic
3774327	I1014V	Pathogenic
3774328	NM_001145304.2(IQCN):c.1061_1062del (p.Tyr354fs)	Pathogenic
2626860	NM_001145304.2(IQCN):c.910C>T (p.Gln304Ter)	Likely pathogenic
4845724	NM_001145304.2(IQCN):c.2547G>A (p.Trp849Ter)	Likely pathogenic
4845830	NM_001145304.2(IQCN):c.3004C>T (p.Gln1002Ter)	Likely pathogenic
4849442	NM_001145304.2(IQCN):c.1523dup (p.Leu508fs)	Likely pathogenic
4849466	NM_001145304.2(IQCN):c.2453del (p.Gln818fs)	Likely pathogenic

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18269594:C:CT	acceptor_gain	0.9900
19:18269595:A:T	acceptor_gain	0.9900
19:18269600:C:CT	acceptor_gain	0.9900
19:18269601:A:T	acceptor_gain	0.9900
19:18269460:TCTTA:T	donor_loss	0.9800
19:18269461:CTTAC:C	donor_loss	0.9800
19:18269462:TTAC:T	donor_loss	0.9800
19:18269463:TACCT:T	donor_loss	0.9800
19:18269464:ACC:A	donor_loss	0.9800
19:18269465:CCTTG:C	donor_loss	0.9800
19:18269603:C:CT	acceptor_gain	0.9800
19:18274399:TCACC:T	donor_loss	0.9800
19:18274400:CA:C	donor_loss	0.9800
19:18274402:CCT:C	donor_loss	0.9800
19:18274424:G:C	donor_gain	0.9600
19:18269588:C:CC	acceptor_gain	0.9500
19:18269600:C:T	acceptor_gain	0.9500
19:18274401:ACCTG:A	donor_gain	0.9500
19:18274402:CCTGC:C	donor_gain	0.9500
19:18269584:TGGG:T	acceptor_gain	0.9400
19:18269586:GG:G	acceptor_gain	0.9400
19:18274401:A:AC	donor_gain	0.9400
19:18274402:C:CC	donor_gain	0.9400
19:18269585:GGGC:G	acceptor_gain	0.9300
19:18274402:CCTG:C	donor_gain	0.9200
19:18269605:C:CT	acceptor_gain	0.9100
19:18267523:CTGC:C	acceptor_gain	0.9000
19:18270727:A:AC	donor_gain	0.9000
19:18270728:C:CC	donor_gain	0.9000
19:18264090:T:TA	donor_gain	0.8800

AlphaMissense

8778 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18267021:G:C	F173L	0.987
19:18267021:G:T	F173L	0.987
19:18267023:A:G	F173L	0.987
19:18267267:G:C	F91L	0.986
19:18267267:G:T	F91L	0.986
19:18267269:A:G	F91L	0.986
19:18257290:C:G	A1145P	0.980
19:18257920:C:G	A935P	0.975
19:18267276:G:C	S88R	0.975
19:18267276:G:T	S88R	0.975
19:18267278:T:G	S88R	0.975
19:18257851:C:G	A958P	0.974
19:18257621:G:C	F1034L	0.973
19:18257621:G:T	F1034L	0.973
19:18257623:A:G	F1034L	0.973
19:18267211:A:G	I110T	0.970
19:18267206:C:G	A112P	0.969
19:18257295:A:T	V1143D	0.966
19:18267268:A:G	F91S	0.963
19:18267120:G:C	F140L	0.961
19:18267120:G:T	F140L	0.961
19:18267122:A:G	F140L	0.961
19:18267221:C:G	A107P	0.960
19:18257353:A:G	W1124R	0.959
19:18257353:A:T	W1124R	0.959
19:18267131:A:G	W137R	0.958
19:18267131:A:T	W137R	0.958
19:18257280:C:G	R1148P	0.957
19:18257518:A:G	C1069R	0.957
19:18257845:A:G	W960R	0.956

dbSNP variants (sampled 300 via entrez): RS1000128963 (19:18266342 T>C), RS1000253499 (19:18275362 T>C), RS1000717083 (19:18268683 G>A,T), RS1000940649 (19:18260160 A>C,G), RS1001194309 (19:18274126 T>C), RS1001320916 (19:18275112 T>A), RS1001391933 (19:18269751 G>T), RS1001546808 (19:18274549 G>A), RS1001588228 (19:18268224 A>G), RS1001766000 (19:18274337 CCA>C), RS1001872175 (19:18270152 G>C), RS1001966084 (19:18258221 A>C), RS1002452093 (19:18259566 G>A), RS1002560238 (19:18260496 C>T), RS1002575833 (19:18263831 C>T)

Disease associations

OMIM: gene MIM:620160 | disease phenotypes: MIM:620170

GenCC curated gene-disease

Mondo (1): spermatogenic failure 78 (MONDO:0859338)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0032561	Microcephalic sperm head
HP:0032562	Tapered sperm head
HP:0033712	Repeated implantation failure

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007876_77	Estimated glomerular filtration rate	2.000000e-10
GCST007932_3	Medication use (thyroid preparations)	9.000000e-15
GCST90016671_4	Visceral adipose tissue volume	4.000000e-08
GCST90020024_534	A body shape index	4.000000e-11
GCST90020025_1431	Waist-to-hip ratio adjusted for BMI	4.000000e-23
GCST90020027_273	Waist-hip index	4.000000e-23

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009933	Thyroid preparation use measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
(+)-JQ1 compound	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
sotorasib	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
propionic acid	increases expression	1
15-acetyldeoxynivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Endosulfan	increases expression	1
Estradiol	decreases expression	1
Smoke	increases expression	1
Dronabinol	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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