CYLC1

Summary

CYLC1 (cylicin 1, HGNC:2582) is a protein-coding gene on chromosome Xq21.1, encoding Cylicin-1 (P35663). Plays a role in the establishment of normal sperm morphology during spermatogenesis and is required for acrosome attachment to the nuclear envelope.

This gene encodes a sperm head cytoskeletal protein. The encoded protein is associated with the calyx of spermatozoa and spermatids. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1538 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 117 total
• Phenotypes (HPO): 7
• MANE Select transcript: NM_021118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2582
Approved symbol	CYLC1
Name	cylicin 1
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183035
Ensembl biotype	protein_coding
OMIM	300768
Entrez	1538

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000329312, ENST00000621735

RefSeq mRNA: 2 — MANE Select: NM_021118 NM_001271680, NM_021118

CCDS: CCDS35341, CCDS75998

Canonical transcript exons

ENST00000329312 — 5 exons

Exon	Start	End
ENSE00001309714	83872886	83874631
ENSE00001364506	83869865	83869905
ENSE00001391227	83871452	83871570
ENSE00001424872	83886552	83886698
ENSE00001459754	83861146	83861199

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 95.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0230 / max 24.5883, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196831	0.0230	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.82	gold quality
male germ cell	CL:0000015	94.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.93	gold quality
left testis	UBERON:0004533	88.52	gold quality
right testis	UBERON:0004534	88.19	gold quality
testis	UBERON:0000473	86.17	gold quality
type B pancreatic cell	CL:0000169	81.84	gold quality
olfactory bulb	UBERON:0002264	81.73	gold quality
cervix squamous epithelium	UBERON:0006922	79.15	gold quality
diaphragm	UBERON:0001103	77.03	gold quality
hair follicle	UBERON:0002073	69.12	gold quality
tongue squamous epithelium	UBERON:0006919	68.58	gold quality
mucosa of urinary bladder	UBERON:0001259	67.80	silver quality
nasal cavity epithelium	UBERON:0005384	67.58	gold quality
superficial temporal artery	UBERON:0001614	67.17	gold quality
epithelium of nasopharynx	UBERON:0001951	65.86	gold quality
epithelial cell of pancreas	CL:0000083	65.17	gold quality
gingival epithelium	UBERON:0001949	64.77	gold quality
cardia of stomach	UBERON:0001162	63.69	gold quality
lower lobe of lung	UBERON:0008949	63.39	silver quality
choroid plexus epithelium	UBERON:0003911	63.15	gold quality
adult organism	UBERON:0007023	62.58	gold quality
saphenous vein	UBERON:0007318	62.52	gold quality
pericardium	UBERON:0002407	62.33	gold quality
body of tongue	UBERON:0011876	62.13	gold quality
nipple	UBERON:0002030	61.84	gold quality
pons	UBERON:0000988	61.77	gold quality
gingiva	UBERON:0001828	61.77	gold quality
substantia nigra pars compacta	UBERON:0001965	61.71	gold quality
synovial joint	UBERON:0002217	61.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1

miRNA regulators (miRDB)

9 targeting CYLC1, 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-4500	99.99	72.72	2367
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-15A-3P	97.47	65.08	527
HSA-MIR-4693-5P	97.35	67.02	1234

Literature-anchored findings (GeneRIF, showing 1)

• Disruption in CYLC1 leads to acrosome detachment, sperm head deformity, and male in/subfertility in humans and mice. (PMID:38573307)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cylc1	ENSMUSG00000073001
rattus_norvegicus	Cylc1	ENSRNOG00000056740

Paralogs (1): CYLC2 (ENSG00000155833)

Protein

Protein identifiers

Cylicin-1 — P35663 (reviewed: P35663)

Alternative names: Cylicin I, Multiple-band polypeptide I

All UniProt accessions (2): P35663, A0A087WXC8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the establishment of normal sperm morphology during spermatogenesis and is required for acrosome attachment to the nuclear envelope.

Subunit / interactions. Interacts with proteins of spermatozoa head including ACTL7A, CCIN, FAM209A and SPACA1; the interactions may be necessary for proper acrosome attachment to the nuclear envelope.

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

Tissue specificity. Testis.

Disease relevance. Spermatogenic failure, X-linked, 8 (SPGFX8) [MIM:301119] A male infertility disorder characterized by a significant reduction in progressive sperm motility, and aberrant sperm morphology. Patient sperm show head and midpiece defects with deformed and detached acrosomes, and flagellar defects. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001258609, NP_066941* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026189	CYLC	Family
IPR029354	Cylicin_N	Domain

Pfam: PF15241

UniProt features (32 total): compositionally biased region 16, repeat 8, region of interest 3, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35663-F1	45.68	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_ACROSOME_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_SECRETORY_VESICLE, GOCC_ACROSOMAL_VESICLE, GOMF_STRUCTURAL_CONSTITUENT_OF_CYTOSKELETON, GOMF_STRUCTURAL_MOLECULE_ACTIVITY

GO Biological Process (4): acrosome assembly (GO:0001675), spermatogenesis (GO:0007283), cytoskeleton organization (GO:0007010), cell differentiation (GO:0030154)

GO Molecular Function (3): structural molecule activity (GO:0005198), structural constituent of cytoskeleton (GO:0005200), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), cytoskeletal calyx (GO:0033150), acrosomal matrix (GO:0043159), sperm head (GO:0061827), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), perinuclear theca (GO:0033011)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
developmental process involved in reproduction	2
cytoskeleton	2
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
male gamete generation	1
organelle organization	1
cellular developmental process	1
molecular_function	1
structural molecule activity	1
cytoskeleton organization	1
binding	1
intracellular membrane-bounded organelle	1
perinuclear theca	1
acrosomal vesicle	1
vacuole	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
perinuclear region of cytoplasm	1

Protein interactions and networks

STRING

1232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYLC1	CCIN	Q13939	979
CYLC1	CCNL1	Q9UK58	578
CYLC1	SATL1	Q86VE3	578
CYLC1	CPXCR1	Q8N123	577
CYLC1	TMEM132E	Q6IEE7	516
CYLC1	APOOL	Q6UXV4	497
CYLC1	ARL13A	Q5H913	490
CYLC1	RPS6KA6	Q9UK32	470
CYLC1	SPACA5B	Q96QH8	468
CYLC1	DYNLT3	P51808	455
CYLC1	RIBC1	Q8N443	452
CYLC1	RNF114	Q9Y508	447
CYLC1	WDR27	A2RRH5	436
CYLC1	AFF2	P51816	418
CYLC1	OR8G1	Q15617	418
CYLC1	PCDH11X	Q9BZA7	418

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CYLC1	SLTM	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (20): SLTM (Proximity Label-MS), ENO1 (Cross-Linking-MS (XL-MS)), CYLC1 (Cross-Linking-MS (XL-MS)), PSMC5 (Cross-Linking-MS (XL-MS)), HIST1H2BN (Cross-Linking-MS (XL-MS)), HIST1H2BD (Cross-Linking-MS (XL-MS)), LOC102724334 (Cross-Linking-MS (XL-MS)), CYLC1 (Cross-Linking-MS (XL-MS)), ACO2 (Cross-Linking-MS (XL-MS)), TEX35 (Cross-Linking-MS (XL-MS)), CYLC1 (Cross-Linking-MS (XL-MS)), HIST1H2BL (Cross-Linking-MS (XL-MS)), HIST2H2BE (Cross-Linking-MS (XL-MS)), CYLC1 (Cross-Linking-MS (XL-MS)), HIST1H2BH (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A060XQP6, A0A1S4FQ37, A2VD23, A3KQQ9, A7E371, B3A0Q3, B3EWZ0, B3EWZ1, B3EWZ4, B7W112, D1FQ14, E9Q9K5, G5EC21, O01949, O16883, O43493, O46203, O55188, O84462, P08721, P10451, P10923, P13665, P14287, P19814, P23498, P31096, P31097, P31098, P31936, P35662, P35663, P98193, Q13316, Q14093, Q28139, Q5MIT9, Q5SRN2, Q5UQ32, Q62313

Diamond homologs: A0A1B0GR13, P35662, P35663, A0A571BEE2, Q14093, Q28092

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

559 predictions. Top by Δscore:

Variant	Effect	Δscore
X:83871451:GTCA:G	acceptor_gain	1.0000
X:83861195:AGGTT:A	donor_gain	0.9900
X:83861196:GGTTG:G	donor_gain	0.9900
X:83861197:GTT:G	donor_gain	0.9900
X:83871450:A:AG	acceptor_gain	0.9900
X:83871451:G:GG	acceptor_gain	0.9900
X:83871571:G:GG	donor_gain	0.9900
X:83861200:G:GG	donor_gain	0.9800
X:83867016:T:G	donor_gain	0.9800
X:83871451:GTC:G	acceptor_gain	0.9800
X:83886530:A:AG	acceptor_gain	0.9800
X:83886531:T:G	acceptor_gain	0.9800
X:83886550:A:AG	acceptor_gain	0.9800
X:83886551:G:GG	acceptor_gain	0.9800
X:83861198:TT:T	donor_gain	0.9700
X:83871450:AGT:A	acceptor_gain	0.9700
X:83886538:A:AG	acceptor_gain	0.9700
X:83871448:TTAG:T	acceptor_gain	0.9600
X:83871449:TAG:T	acceptor_gain	0.9600
X:83884764:A:AG	acceptor_gain	0.9600
X:83886538:ACTTT:A	acceptor_gain	0.9600
X:83861198:TTG:T	donor_loss	0.9500
X:83861199:TG:T	donor_loss	0.9500
X:83861200:G:T	donor_loss	0.9500
X:83871451:GT:G	acceptor_gain	0.9500
X:83874628:TTTGG:T	donor_loss	0.9500
X:83874629:TTGGT:T	donor_loss	0.9500
X:83874630:TGGTA:T	donor_loss	0.9500
X:83874632:G:GG	donor_gain	0.9500
X:83874632:GTA:G	donor_loss	0.9500

AlphaMissense

4313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:83886564:T:A	W646R	0.975
X:83886564:T:C	W646R	0.975
X:83886566:G:C	W646C	0.972
X:83886566:G:T	W646C	0.972
X:83886568:T:C	I647T	0.969
X:83886577:T:C	L650P	0.946
X:83874470:T:C	F588L	0.939
X:83874472:C:A	F588L	0.939
X:83874472:C:G	F588L	0.939
X:83886568:T:G	I647S	0.938
X:83886580:T:A	L651H	0.932
X:83871502:T:C	F37L	0.919
X:83871504:T:A	F37L	0.919
X:83871504:T:G	F37L	0.919
X:83874630:T:C	L641S	0.919
X:83886580:T:C	L651P	0.915
X:83886565:G:C	W646S	0.894
X:83886565:G:T	W646L	0.893
X:83886568:T:A	I647N	0.871
X:83874520:A:C	R604S	0.865
X:83874520:A:T	R604S	0.865
X:83874624:C:A	A639D	0.864
X:83874619:A:C	R637S	0.862
X:83874619:A:T	R637S	0.862
X:83872936:G:C	W76C	0.859
X:83872936:G:T	W76C	0.859
X:83873006:T:C	F100L	0.850
X:83873008:C:A	F100L	0.850
X:83873008:C:G	F100L	0.850
X:83886575:G:C	K649N	0.848

dbSNP variants (sampled 300 via entrez): RS1000029711 (X:83882728 T>C), RS1000242058 (X:83866783 T>G), RS1000406589 (X:83866072 C>T), RS1000444599 (X:83883200 C>T), RS1000845723 (X:83869309 C>A,T), RS1000851132 (X:83872662 C>A), RS1000903494 (X:83873038 T>A,C), RS1001048362 (X:83881546 C>A,T), RS1001333448 (X:83881897 C>T), RS1001411798 (X:83886660 A>C,G), RS1001440028 (X:83881068 T>A), RS1001475275 (X:83863390 G>C), RS1001586004 (X:83876259 C>T), RS1001798402 (X:83863811 T>C), RS1001910470 (X:83870871 C>T)

Disease associations

OMIM: gene MIM:300768 | disease phenotypes: MIM:301119

GenCC curated gene-disease

Mondo (1): spermatogenic failure, X-linked, 8 (MONDO:0970943)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000798	Oligozoospermia
HP:0001417	X-linked inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012865	Abnormal sperm head morphology
HP:0032560	Coiled sperm flagella
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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Rotenone	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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