CATSPER2

protein-coding

cation channel sperm associated 2, the group of Cation channels sperm associated

Gene summary

This gene encodes a member of a family of cation channel proteins that localize to the flagellum of spermatozoa. Defects at this locus causes male infertility. Alternatively spliced transcript variants have been observed at this locus. Readthrough transcription originates upstream of this locus in diphosphoinositol pentakisphosphate kinase 1 pseudogene 1 and is represented by GeneID:110006325. Related pseudogenes are found next to this locus on chromosome 15 and on chromosome 5. [provided by RefSeq, Mar 2017]

MANE transcript

NM_172095.4

Inheritance

—

ClinVar variants

U:90B:35

Top phenotype

CATSPER2-related condition

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr15:43,628,503-43,668,118

External References & Databases

Ensembl (ENSG00000166762)

Transcript & Mutation Effects

hg38 • Region Span ~39.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CATSPER2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 116

not providedTotal: 15

CATSPER2-related conditionTotal: 7

Infertility disorderTotal: 1

Male infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172095.4. 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				14 clinvar		14
missense			86 clinvar	18 clinvar	2 clinvar	106
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar	1 clinvar		4
Total	0	0	90	33	2	125

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172095.4	RefSeq	NP_742093.1	12	MANE Select
ENST00000396879.8	Ensembl	ENSP00000380088.3	12	MANE Select
NM_001282309.3	RefSeq	NP_001269238.1	12	Standard
NM_001282310.2	RefSeq	NP_001269239.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fertilization
Reproduction
Sperm Motility And Taxes

Biological Process

multicellular organism development
fertilization
flagellated sperm motility
regulation of ion transmembrane transport
sperm-egg recognition

Molecular Function

calcium activated cation channel activity
voltage-gated ion channel activity
calcium channel activity
protein binding

Cellular Component

plasma membrane
motile cilium
CatSper complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321596
Coding exons: 12
Length: 39616
Individuals with no LoFs: 61886
Homozygous LoFs: 13954
Heterozygous LoFs: 49898
Defined: 125738
p: 0.298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.750	321	285	1.12	0.0000171	3462
Missense (PolyPhen)		78	83.152	0.93804		1060
Synonymous	-0.940	118	106	1.12	0.00000592	1013
Loss of Function	0.576	27	30.4	0.887	0.00000168	332

Population LoF Frequency

Population	CAF	p-value	Status
African	0.71	0.63	notable
Latino/Admixed American	0.30	0.30	notable
Ashkenazi Jewish	0.38	0.37	notable
East Asian	0.33	0.32	notable
Finnish	0.18	0.17	notable
European (Non-Finnish)	0.27	0.27	notable
South Asian	0.36	0.35	notable
Other	0.31	0.29	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Voltage-gated calcium channel that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the oocyte. {ECO:0000269|PubMed:21412338, ECO:0000269|PubMed:21412339}.;

Recessive Scores

pRec: 0.0651

Intolerance Scores

LoFtool: 0.164
RVIS EVS: 0.91
RVIS percentile EVS: 89.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0359

Gene Damage Prediction

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