IQCF1

Summary

IQCF1 (IQ motif containing F1, HGNC:28607) is a protein-coding gene on chromosome 3p21.2, encoding IQ domain-containing protein F1 (Q8N6M8). Involved in sperm capacitation and acrosome reaction.

Predicted to enable calmodulin binding activity. Predicted to be involved in positive regulation of acrosome reaction and positive regulation of flagellated sperm motility involved in capacitation. Located in acrosomal vesicle.

Source: NCBI Gene 132141 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_152397

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28607
Approved symbol	IQCF1
Name	IQ motif containing F1
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC39725
Ensembl gene	ENSG00000173389
Ensembl biotype	protein_coding
OMIM	621131
Entrez	132141

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000310914, ENST00000314534

RefSeq mRNA: 1 — MANE Select: NM_152397 NM_152397

CCDS: CCDS2836

Canonical transcript exons

ENST00000310914 — 4 exons

Exon	Start	End
ENSE00001252763	51902985	51903089
ENSE00003475585	51894876	51895336
ENSE00003583832	51896832	51896894
ENSE00003846098	51903270	51903353

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 96.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0885 / max 92.0213, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42369	0.0885	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.51	gold quality
left testis	UBERON:0004533	95.89	gold quality
right testis	UBERON:0004534	95.48	gold quality
testis	UBERON:0000473	92.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.59	gold quality
adult organism	UBERON:0007023	75.60	gold quality
buccal mucosa cell	CL:0002336	65.22	gold quality
tendon of biceps brachii	UBERON:0008188	62.48	gold quality
medial globus pallidus	UBERON:0002477	52.34	gold quality
globus pallidus	UBERON:0001875	49.67	gold quality
right coronary artery	UBERON:0001625	47.09	gold quality
endocervix	UBERON:0000458	45.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	45.82	silver quality
cerebellar hemisphere	UBERON:0002245	45.81	silver quality
middle temporal gyrus	UBERON:0002771	45.56	gold quality
cerebellar cortex	UBERON:0002129	45.50	silver quality
cerebellum	UBERON:0002037	45.03	silver quality
right uterine tube	UBERON:0001302	44.43	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
amniotic fluid	UBERON:0000173	43.28	gold quality
upper leg skin	UBERON:0004262	42.91	silver quality
secondary oocyte	CL:0000655	42.57	gold quality
tendon	UBERON:0000043	42.57	gold quality
uterine cervix	UBERON:0000002	42.41	gold quality
right ovary	UBERON:0002118	42.29	silver quality
colonic epithelium	UBERON:0000397	42.10	gold quality
ectocervix	UBERON:0012249	42.10	gold quality
substantia nigra pars compacta	UBERON:0001965	41.52	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.79
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• a newly identified acrosomal protein, IQCF1, is closely related to sperm capacitation and AR; in particular, it is involved in tyrosine phosphorylation of sperm proteins through interaction with CaM (PMID:25380116)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Iqcf1	ENSMUSG00000066383
rattus_norvegicus	Iqcf1	ENSRNOG00000037289

Paralogs (4): IQCF2 (ENSG00000184345), IQCF5 (ENSG00000214681), IQCF6 (ENSG00000214686), IQCF3 (ENSG00000229972)

Protein

Protein identifiers

IQ domain-containing protein F1 — Q8N6M8 (reviewed: Q8N6M8)

All UniProt accessions (2): Q8N6M8, F8WEK8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in sperm capacitation and acrosome reaction.

Subunit / interactions. Interacts with calmodulin.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N6M8-1	1	yes
Q8N6M8-2	2

RefSeq proteins (1): NP_689610* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR039887	IQCF	Family

Pfam: PF00612

UniProt features (10 total): domain 2, compositionally biased region 2, splice variant 2, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6M8-F1	77.41	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOCC_SECRETORY_GRANULE, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_MATURATION, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, TGANTCA_AP1_C, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM

GO Biological Process (2): positive regulation of flagellated sperm motility involved in capacitation (GO:0060474), positive regulation of acrosome reaction (GO:2000344)

GO Molecular Function (2): calmodulin binding (GO:0005516), protein binding (GO:0005515)

GO Cellular Component (2): acrosomal vesicle (GO:0001669), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
reproductive process	1
sperm capacitation	1
positive regulation of flagellated sperm motility	1
acrosome reaction	1
regulation of acrosome reaction	1
positive regulation of reproductive process	1
protein binding	1
binding	1
secretory granule	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQCF1	KLHL10	Q6JEL2	664
IQCF1	CCDC83	Q8IWF9	623
IQCF1	ANKRD9	Q96BM1	572
IQCF1	ZNF706	Q9Y5V0	539
IQCF1	CNBD2	Q96M20	531
IQCF1	CCDC182	A6NF36	529
IQCF1	FSCN3	Q9NQT6	525
IQCF1	CCDC181	Q5TID7	523
IQCF1	TNP2	Q05952	511
IQCF1	FAM229B	Q4G0N7	497
IQCF1	FAM170B	A6NMN3	476
IQCF1	DRC9	Q9H095	474
IQCF1	SPEM1	Q8N4L4	471
IQCF1	DMRTC2	Q8IXT2	459
IQCF1	TSSK6	Q9BXA6	455

IntAct

2 interactions, top by confidence:

A	B	Type	Score
IQCF1	DOK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): ATP2A3 (Affinity Capture-MS), PEX19 (Affinity Capture-MS), FAR2 (Affinity Capture-MS), RETSAT (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), CAMK2D (Affinity Capture-MS), TYW1B (Affinity Capture-MS), EPHX1 (Affinity Capture-MS), MZT2B (Affinity Capture-MS), SNX14 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), TFIP11 (Affinity Capture-MS), MUL1 (Affinity Capture-MS), DDRGK1 (Affinity Capture-MS), DOK2 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Q7, A4D126, A4II32, A6NCI4, A8K8P3, A8MTL0, A8MYZ5, A9CB34, E0CYC6, F1QWK4, O14772, O15554, O89109, P0C7M6, P0C8N6, Q05AA6, Q08CB3, Q13474, Q1HAQ0, Q1LWG4, Q2M2U5, Q32KU4, Q3SYS7, Q3TFD2, Q3UVV9, Q4AC99, Q5I0I4, Q5R796, Q5RFS1, Q8BHD4, Q8BP00, Q8BPW0, Q8CB65, Q8CHT6, Q8IXL9, Q8K2I9, Q8N0W5, Q8N6M8, Q8NEA4, Q8NF37

Diamond homologs: A8MTL0, A8MYZ5, P0C7M6, Q2M2U5, Q32KU4, Q3SYS7, Q6AXX0, Q8IXL9, Q8N6M8, Q9D498, Q9D9K8, Q9DAL7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

474 predictions. Top by Δscore:

Variant	Effect	Δscore
3:51896830:A:AC	donor_gain	1.0000
3:51896831:C:CC	donor_gain	1.0000
3:51896826:TCATA:T	donor_loss	0.9900
3:51896827:CATAC:C	donor_loss	0.9900
3:51896828:ATACT:A	donor_loss	0.9900
3:51896829:TACTT:T	donor_loss	0.9900
3:51896830:A:C	donor_loss	0.9900
3:51896831:C:CA	donor_loss	0.9900
3:51896831:CT:C	donor_gain	0.9900
3:51902979:TCCTA:T	donor_loss	0.9900
3:51902980:CCTA:C	donor_loss	0.9900
3:51902981:CTA:C	donor_loss	0.9900
3:51902982:TA:T	donor_loss	0.9900
3:51902984:C:CA	donor_loss	0.9900
3:51902984:CCT:C	donor_gain	0.9900
3:51895338:T:C	acceptor_gain	0.9800
3:51896825:GTCAT:G	donor_loss	0.9800
3:51896831:CTT:C	donor_gain	0.9800
3:51896895:C:CC	acceptor_gain	0.9800
3:51896906:A:C	acceptor_gain	0.9800
3:51903090:C:CC	acceptor_gain	0.9800
3:51895336:GC:G	acceptor_loss	0.9700
3:51895337:C:CA	acceptor_loss	0.9700
3:51895337:C:CC	acceptor_gain	0.9700
3:51895338:T:TC	acceptor_gain	0.9700
3:51895342:A:T	acceptor_gain	0.9700
3:51896831:CTTT:C	donor_gain	0.9700
3:51896890:TTAGC:T	acceptor_gain	0.9700
3:51896895:C:CA	acceptor_loss	0.9700
3:51896896:T:C	acceptor_loss	0.9700

AlphaMissense

1316 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:51895145:G:C	F121L	0.922
3:51895145:G:T	F121L	0.922
3:51895147:A:G	F121L	0.922
3:51895097:C:A	M137I	0.890
3:51895097:C:G	M137I	0.890
3:51895097:C:T	M137I	0.890
3:51895204:A:G	W102R	0.882
3:51895204:A:T	W102R	0.882
3:51895269:C:G	R80P	0.881
3:51895273:A:G	W79R	0.877
3:51895273:A:T	W79R	0.877
3:51895202:C:A	W102C	0.858
3:51895202:C:G	W102C	0.858
3:51895255:G:T	R85S	0.852
3:51894951:A:G	I186T	0.848
3:51895237:C:G	A91P	0.847
3:51895280:C:A	Q76H	0.843
3:51895280:C:G	Q76H	0.843
3:51895284:A:G	I75T	0.842
3:51895279:C:G	A77P	0.837
3:51895101:C:G	R136P	0.834
3:51895102:G:T	R136S	0.834
3:51895215:A:G	I98T	0.831
3:51895254:C:G	R85P	0.819
3:51895276:A:G	W78R	0.819
3:51895276:A:T	W78R	0.819
3:51895251:C:G	R86P	0.817
3:51895112:C:A	Q132H	0.816
3:51895112:C:G	Q132H	0.816
3:51895043:C:A	Q155H	0.811

dbSNP variants (sampled 300 via entrez): RS1000047768 (3:51903945 C>T), RS1000062819 (3:51896967 G>A,C), RS1001561934 (3:51898106 G>A,C), RS1001734149 (3:51898406 G>A), RS1002294103 (3:51899566 C>G), RS1002484994 (3:51899999 T>C), RS1002728385 (3:51894625 T>C), RS1002815444 (3:51901934 A>G), RS1003031981 (3:51894901 T>A), RS1003518419 (3:51900450 C>T), RS1003558553 (3:51901597 A>T), RS1004050234 (3:51903168 C>A,G,T), RS1004187603 (3:51903497 G>A), RS1004944303 (3:51902422 A>G), RS1005059199 (3:51901691 C>G)

Disease associations

OMIM: gene MIM:621131 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010002_423	Refractive error	8.000000e-09
GCST010241_392	Apolipoprotein A1 levels	9.000000e-10
GCST010242_354	HDL cholesterol levels	9.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
Methotrexate	decreases expression	1
Quercetin	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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