CABYR

protein-coding

calcium binding tyrosine phosphorylation regulated

Gene summary

To reach fertilization competence, spermatozoa undergo a series of morphological and molecular maturational processes, termed capacitation, involving protein tyrosine phosphorylation and increased intracellular calcium. The protein encoded by this gene localizes to the principal piece of the sperm flagellum in association with the fibrous sheath and exhibits calcium-binding when phosphorylated during capacitation. A pseudogene on chromosome 3 has been identified for this gene. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

MANE transcript

NM_153769.3

Inheritance

—

ClinVar variants

U:27

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr18:24,138,987-24,161,600

External References & Databases

Ensembl (ENSG00000154040)

Transcript & Mutation Effects

hg38 • Region Span ~22.6 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 CABYR variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 79

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153769.3. 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						0
missense			25 clinvar			25
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	27	0	0	27

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153769.3	RefSeq	NP_722453.1	5	MANE Select
ENST00000399496.8	Ensembl	ENSP00000382419.3	5	MANE Select
NM_001308231.2	RefSeq	NP_001295160.1	1	Standard
NM_012189.4	RefSeq	NP_036321.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

epithelial cilium movement
sperm capacitation

Molecular Function

calcium ion binding
SH3 domain binding
protein heterodimerization activity

Cellular Component

nucleus
cytoplasm
cytosol
cytoskeleton
motile cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399496
Coding exons: 4
Length: 22626
Individuals with no LoFs: 124275
Homozygous LoFs: 56
Heterozygous LoFs: 1417
Defined: 125748
p: 0.00587

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.410	184	200	0.919	0.00000988	2441
Missense (PolyPhen)		68	78.683	0.86423		1033
Synonymous	0.445	69	73.9	0.934	0.00000413	783
Loss of Function	1.18	11	16.1	0.682	7.86e-7	204

Population LoF Frequency

Population	CAF	p-value	Status
African	0.078	0.076	notable
Latino/Admixed American	0.0049	0.0048	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00063	0.00062	rare
South Asian	0.00044	0.00042	rare
Other	0.0033	0.0033	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as a regulator of both motility- and head- associated functions such as capacitation and the acrosome reaction. Isoform 1 binds calcium in vitro. Isoform 2 and isoform 6 probably bind calcium. Isoform 3 and isoform 5 do not bind calcium in vitro. Isoform 4 probably does not bind calcium.;

Recessive Scores

pRec: 0.0546

Intolerance Scores

LoFtool: 0.731
RVIS EVS: 0.11
RVIS percentile EVS: 61.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0322

Gene Damage Prediction

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