CYLC1

protein-coding

cylicin 1

Gene summary

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. [provided by RefSeq, Nov 2012]

MANE transcript

NM_021118.3

Inheritance

ClinVar variants

U:104B:8

Top phenotype

Spermatogenic failure, X-linked, 8

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chrX:83,861,126-83,886,699

External References & Databases

Ensembl (ENSG00000183035)

Transcript & Mutation Effects

hg38 • Region Span ~25.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Spermatogenic failure, X-linked, 8XL

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 38013430; 38573307

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYLC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 7

Spermatogenic failure, X-linked, 8Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021118.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	4 clinvar		13
missense			89 clinvar	4 clinvar		93
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	104	8	0	112

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021118.3	RefSeq	NP_066941.1	5	MANE Select
ENST00000329312.5	Ensembl	ENSP00000331556.4	5	MANE Select
NM_001271680.2	RefSeq	NP_001258609.1	4	Standard
ENST00000621735.4	Ensembl	ENSP00000480907.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cytoskeleton organization
multicellular organism development
spermatogenesis
cell differentiation

Molecular Function

structural molecule activity
structural constituent of cytoskeleton

Cellular Component

nucleus
cytoskeletal calyx
acrosomal matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329312
Coding exons: 5
Length: 25552
Individuals with no LoFs: 115979
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 115980
p: 0.00000431

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.53	241	183	1.32	0.0000120	4278
Missense (PolyPhen)		49	32.006	1.531		801
Synonymous	-1.63	84	67.1	1.25	0.00000445	1132
Loss of Function	3.08	1	12.9	0.0773	8.20e-7	416

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000013	0.0000094	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possible architectural role during spermatogenesis. May be involved in spermatid differentiation.;

Recessive Scores

pRec: 0.0626

Intolerance Scores

LoFtool: 0.120
RVIS EVS: 0.77
RVIS percentile EVS: 87.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0278

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium