CCDC146

protein-coding

coiled-coil domain containing 146

Gene summary

Involved in spermatid development. Located in several cellular components, including microtubule organizing center; midbody; and sperm flagellum. Implicated in spermatogenic failure 94. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_020879.3

Inheritance

ClinVar variants

P:9U:130B:5

Top phenotype

Spermatogenic failure 94

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr7:77,122,434-77,329,533

External References & Databases

Ensembl (ENSG00000135205)

Transcript & Mutation Effects

hg38 • Region Span ~207.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0018393

Submitter: King Faisal Specialist Hospital and Research Center

Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). The gene is scored according to ClinGen classification. Moderate with total score of 8. Single variant segregation (3 points), experimental evidence: Animal model (4 points) and testicular expression (1 points) (PMID:24309898).

Clinical Genomic Database (CGD)

Spermatogenic failure 94AR

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: 38441556

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCDC146 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 146

Spermatogenic failure 94Total: 8

not providedTotal: 5

Male infertility due to sperm motility disorderTotal: 2

Male infertility with spermatogenesis disorder due to single gene mutationTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020879.3. 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			1 clinvar	1 clinvar		2
missense	1 clinvar		121 clinvar	4 clinvar		126
nonsense	1 clinvar	1 clinvar				2
start loss						0
frameshift	2 clinvar	3 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)		1 clinvar	7 clinvar			8
Total	4	5	130	5	0	144

Highest pathogenic variant AF is 0.000058248843

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020879.3	RefSeq	NP_065930.2	18	MANE Select
ENST00000285871.5	Ensembl	ENSP00000285871.4	18	MANE Select
ENST00000415750.5	Ensembl	ENSP00000388649.1	4	Standard
ENST00000890162.1	Ensembl	ENSP00000560221.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

centriole

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000285871
Coding exons: 18
Length: 207100
Individuals with no LoFs: 125451
Homozygous LoFs: 3
Heterozygous LoFs: 294
Defined: 125748
p: 0.00118

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.878	425	479	0.887	0.0000247	6346
Missense (PolyPhen)		68	89.145	0.7628		1231
Synonymous	-0.736	182	170	1.07	0.00000876	1634
Loss of Function	1.11	45	53.8	0.836	0.00000302	676

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00063	0.00062	rare
Latino/Admixed American	0.0015	0.0015	notable
Ashkenazi Jewish	0.0067	0.0067	notable
East Asian	0.0019	0.0019	notable
Finnish	0.00019	0.00014	rare
European (Non-Finnish)	0.00066	0.00064	rare
South Asian	0.0018	0.0017	notable
Other	0.0012	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.620
RVIS EVS: 0.67
RVIS percentile EVS: 84.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.891

Gene Damage Prediction

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