CCIN

Summary

CCIN (calicin, HGNC:1568) is a protein-coding gene on chromosome 9p13.3, encoding Calicin (Q13939). Required for both nuclear and acrosomal shaping during spermiogenesis.

The protein encoded by this gene is a basic protein of the sperm head cytoskeleton. This protein contains kelch repeats and a BTB/POZ domain and is necessary for normal morphology during sperm differentiation. This gene is intronless.

Source: NCBI Gene 881 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total — 5 pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_005893

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1568
Approved symbol	CCIN
Name	calicin
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KBTBD14, BTBD20
Ensembl gene	ENSG00000185972
Ensembl biotype	protein_coding
OMIM	603960
Entrez	881

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000335119

RefSeq mRNA: 1 — MANE Select: NM_005893 NM_005893

CCDS: CCDS6599

Canonical transcript exons

ENST00000335119 — 1 exons

Exon	Start	End
ENSE00001334442	36169388	36171334

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 93.71.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2055 / max 202.0861, expressed in 4 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96673	0.1338	4
96672	0.0687	3
96671	0.0030	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	93.71	gold quality
right testis	UBERON:0004534	93.24	gold quality
testis	UBERON:0000473	90.94	gold quality
sperm	CL:0000019	87.46	gold quality
male germ cell	CL:0000015	87.38	gold quality
adult organism	UBERON:0007023	86.18	gold quality
endometrium epithelium	UBERON:0004811	80.25	gold quality
type B pancreatic cell	CL:0000169	78.51	gold quality
olfactory bulb	UBERON:0002264	73.68	gold quality
tongue squamous epithelium	UBERON:0006919	70.85	gold quality
diaphragm	UBERON:0001103	69.65	gold quality
triceps brachii	UBERON:0001509	69.32	gold quality
gluteal muscle	UBERON:0002000	68.15	gold quality
smooth muscle tissue	UBERON:0001135	67.56	gold quality
biceps brachii	UBERON:0001507	66.93	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.32	gold quality
frontal pole	UBERON:0002795	64.96	gold quality
paraflocculus	UBERON:0005351	64.11	gold quality
middle frontal gyrus	UBERON:0002702	63.60	gold quality
cervix epithelium	UBERON:0004801	61.70	gold quality
epithelial cell of pancreas	CL:0000083	61.43	gold quality
cervix squamous epithelium	UBERON:0006922	60.66	gold quality
stromal cell of endometrium	CL:0002255	60.60	gold quality
myocardium	UBERON:0002349	60.53	gold quality
lateral nuclear group of thalamus	UBERON:0002736	60.35	gold quality
upper arm skin	UBERON:0004263	60.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	59.43	gold quality
Brodmann (1909) area 10	UBERON:0013541	59.11	gold quality
tendon of biceps brachii	UBERON:0008188	59.10	gold quality
quadriceps femoris	UBERON:0001377	58.38	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccin	ENSMUSG00000070999
rattus_norvegicus	Ccin	ENSRNOG00000014831

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359)

Protein

Protein identifiers

Calicin — Q13939 (reviewed: Q13939)

All UniProt accessions (2): Q13939, Q8WX35

UniProt curated annotations — full annotation on UniProt →

Function. Required for both nuclear and acrosomal shaping during spermiogenesis.

Subunit / interactions. Interacts with CYLC1; the interaction may be relevant for proper acrosome attachment to the nuclear envelope.

Subcellular location. Cytoplasm. Cytoskeleton. Perinuclear theca. Calyx.

Tissue specificity. Expressed in testis, in spermatozoa (at protein level).

Disease relevance. Spermatogenic failure 91 (SPGF91) [MIM:620838] An autosomal recessive, male infertility disorder due to globozoospermia and asthenoteratozoospermia. Patient sperm show defects of the head, including a misshapen rounded head and detachment of the acrosome, and the sperm fail to attach to the zona pellucida of the egg. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_005884* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006652	Kelch_1	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR017096	BTB-kelch_protein	Family
IPR048070	Calicin_BTB_POZ	Domain

Pfam: PF00651, PF07707, PF13964

UniProt features (19 total): sequence variant 6, repeat 6, sequence conflict 3, domain 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13939-F1	90.53	0.72

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 (1): 149

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GGGTGGRR_PAX4_03, MORF_IL4, chr9p13, GNF2_CCNA1, ATF3_Q6, WEBER_METHYLATED_LCP_IN_SPERM_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, PIT1_Q6, NKX3A_01, GOBP_PROTEIN_CATABOLIC_PROCESS, TGGAAA_NFAT_Q4_01, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (3): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), Cul3-RING ubiquitin ligase complex (GO:0031463), cytoskeletal calyx (GO:0033150), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
enzyme-substrate adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1
perinuclear theca	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCIN	CYLC1	P35663	979
CCIN	CYLC2	Q14093	962
CCIN	DPY19L2	Q6NUT2	496
CCIN	ACTRT1	Q8TDG2	482
CCIN	SPATA16	Q9BXB7	451
CCIN	VPS54	Q9P1Q0	447
CCIN	OR1L1	Q8NH94	447
CCIN	GBE1	Q04446	441
CCIN	SPACA1	Q9HBV2	412
CCIN	ACTRT2	Q8TDY3	398
CCIN	OR1J1	Q8NGS3	390
CCIN	ZPBP	Q9BS86	377
CCIN	GOPC	Q9HD26	377
CCIN	CALML6	Q8TD86	375
CCIN	CALML3	P27482	375

IntAct

15 interactions, top by confidence:

A	B	Type	Score
PRKN	CCIN	psi-mi:“MI:0915”(physical association)	0.560
VHL	CCIN	psi-mi:“MI:0915”(physical association)	0.560
HTT	CCIN	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	CCIN	psi-mi:“MI:0915”(physical association)	0.560
CCIN	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
CCIN	CCZ1B	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): CCIN (Synthetic Lethality), HSP90AB4P (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), HSPA1L (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), NUDCD3 (Affinity Capture-MS), CCIN (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A0A1B8YAB1, B1H285, B3DIV9, E9QIN8, E9QJ30, F1QEG2, O88879, Q08CL3, Q08CY1, Q0D2A9, Q13939, Q28068, Q3UQV5, Q3ZCT8, Q503R4, Q5F3N5, Q5R4S6, Q5R663, Q5RG82, Q5XHZ6, Q5XI58, Q5ZI33, Q69ZK5, Q6DFF7, Q6DFU2, Q6Q7X9, Q6V595, Q7ZVQ8, Q86V97, Q8BHI4, Q8BUL5, Q8BWA5, Q8CA72, Q8CDE2, Q8CE33, Q8IXQ5, Q8NAB2, Q8NFY9, Q8R179, Q8WVZ9

Diamond homologs: A0JN76, A1L2U9, A1YPR0, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, E1B932, G5E8B9, G5ED84, O14867, O15062, O15209, O35260, O43298, O88939, O93567, O95365, O95625, P28575, P41182, P41183, P97302, P97303, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q13939, Q14526, Q1L8W0, Q1LYM6, Q2WGJ6, Q3B7N9, Q3SWU4, Q53G59, Q562B4, Q5R5N5, Q5TC79

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CCIN	up-regulates	F-actin_assembly

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	74
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1525990	NM_005893.3(CCIN):c.853G>A (p.Gly285Ser)	Pathogenic
3236746	NM_005893.3(CCIN):c.125A>T (p.His42Leu)	Pathogenic
3236747	NM_005893.3(CCIN):c.1294C>T (p.Arg432Trp)	Pathogenic
3236748	NM_005893.3(CCIN):c.1341C>A (p.Cys447Ter)	Pathogenic
3236749	NM_005893.3(CCIN):c.230T>C (p.Leu77Pro)	Pathogenic

SpliceAI

224 predictions. Top by Δscore:

Variant	Effect	Δscore
9:36170806:TGA:T	donor_gain	0.9600
9:36170833:T:TA	donor_gain	0.9600
9:36170834:A:AA	donor_gain	0.9600
9:36170808:AAAG:A	donor_gain	0.9500
9:36170774:GCA:G	donor_gain	0.9100
9:36170794:G:GT	donor_gain	0.9000
9:36170815:A:AG	donor_gain	0.8600
9:36170835:G:GG	donor_gain	0.8600
9:36170727:A:G	donor_gain	0.8500
9:36170813:T:TA	donor_gain	0.8400
9:36170616:ACCT:A	donor_gain	0.8300
9:36170814:T:A	donor_gain	0.8300
9:36170812:GT:G	donor_gain	0.7900
9:36170703:G:GT	donor_gain	0.7800
9:36170767:G:GT	donor_gain	0.7700
9:36170723:A:T	donor_gain	0.7400
9:36170827:TCG:T	donor_gain	0.7300
9:36170617:C:G	donor_gain	0.6900
9:36170816:T:G	donor_gain	0.6900
9:36170801:C:CG	donor_gain	0.6500
9:36170807:GAA:G	donor_gain	0.6100
9:36170775:C:T	donor_gain	0.6000
9:36170836:T:TG	donor_gain	0.5800
9:36170837:G:GG	donor_gain	0.5800
9:36170838:G:GG	donor_gain	0.5800
9:36170897:C:CT	acceptor_gain	0.5400
9:36170895:TTC:T	acceptor_gain	0.5200
9:36170800:GCTT:G	donor_gain	0.5100
9:36170722:G:GT	donor_gain	0.4800
9:36170832:G:GT	donor_gain	0.4800

AlphaMissense

3896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:36170709:T:A	W403R	0.998
9:36170709:T:C	W403R	0.998
9:36169568:G:C	R22S	0.997
9:36169568:G:T	R22S	0.997
9:36170112:T:A	W204R	0.997
9:36170112:T:C	W204R	0.997
9:36170503:G:A	G334D	0.997
9:36170565:T:A	W355R	0.997
9:36170565:T:C	W355R	0.997
9:36170601:T:C	F367L	0.997
9:36170603:C:A	F367L	0.997
9:36170603:C:G	F367L	0.997
9:36170644:G:A	G381D	0.997
9:36170647:G:A	G382E	0.997
9:36169567:G:C	R22T	0.996
9:36170185:T:A	V228D	0.996
9:36170467:C:A	A322D	0.996
9:36170500:G:A	G333D	0.996
9:36170646:G:T	G382W	0.996
9:36170114:G:C	W204C	0.995
9:36170114:G:T	W204C	0.995
9:36170634:T:G	Y378D	0.995
9:36171180:T:A	W560R	0.995
9:36171180:T:C	W560R	0.995
9:36169862:T:G	C120W	0.994
9:36170104:T:C	L201P	0.994
9:36170421:T:A	W307R	0.994
9:36170421:T:C	W307R	0.994
9:36170500:G:T	G333V	0.994
9:36170503:G:T	G334V	0.994

dbSNP variants (sampled 300 via entrez): RS1000447808 (9:36168391 T>A,C), RS1000925798 (9:36168074 CTG>C), RS1001105715 (9:36167844 A>G), RS1002663010 (9:36171069 G>A), RS1004669722 (9:36168427 T>C), RS1004882222 (9:36168965 C>A,T), RS1005299297 (9:36168789 T>A), RS1005886106 (9:36167480 C>T), RS1006816052 (9:36171590 C>T), RS1006872459 (9:36171583 T>G), RS1006874881 (9:36171665 C>T), RS1007336903 (9:36171283 G>C,T), RS1007899869 (9:36170046 C>A,T), RS1008943025 (9:36169178 C>A,G,T), RS1009530247 (9:36167811 G>A)

Disease associations

OMIM: gene MIM:603960 | disease phenotypes: MIM:620838

GenCC curated gene-disease

Mondo (1): spermatogenic failure 91 (MONDO:0970952)

Orphanet (0):

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012205	Globozoospermia
HP:0012207	Reduced sperm motility
HP:0033393	Irregularly shaped sperm tail
HP:0034011	Reduced progressive sperm motility

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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Glyphosate	decreases expression	1
Cyclophosphamide	increases expression	1
Endosulfan	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Vanadates	increases expression	1

Clinical trials (associated diseases)

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