CRISP1

protein-coding

cysteine rich secretory protein 1, the group of Cysteine rich secretory protein family

Gene summary

Fertilization consists of a sequence of specific cell-cell interactions culminating in the fusion of the sperm and egg plasma membranes. Recognition, binding, and fusion occur through the interaction of complementary molecules that are localized to specific domains of the sperm and egg plasma membranes. In the sperm, the postacrosomal region or equatorial segment is involved in sperm-egg plasma membrane fusion. The protein encoded by this gene is a member of the cysteine-rich secretory protein (CRISP) family. It is expressed in the epididymis, is secreted into the epididymal lumen, and binds to the postacrosomal region of the sperm head, where it plays a role in sperm-egg fusion. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

Previous symbols:

AEGL1

MANE transcript

NM_001131.3

Inheritance

—

ClinVar variants

U:44B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr6:49,834,257-49,877,096

External References & Databases

Ensembl (ENSG00000124812)

Transcript & Mutation Effects

hg38 • Region Span ~42.8 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 CRISP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001131.3. 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	2 clinvar		3
missense			43 clinvar	6 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	44	8	0	52

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001131.3	RefSeq	NP_001122.2	7	MANE Select
ENST00000335847.9	Ensembl	ENSP00000338276.4	7	MANE Select
NM_001205220.2	RefSeq	NP_001192149.1	7	Standard
NM_170609.2	RefSeq	NP_733758.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

binding of sperm to zona pellucida
fusion of sperm to egg plasma membrane involved in single fertilization
regulation of acrosome reaction

Molecular Function

calcium channel regulator activity

Cellular Component

extracellular space
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335847
Coding exons: 7
Length: 42840
Individuals with no LoFs: 125315
Homozygous LoFs: 5
Heterozygous LoFs: 423
Defined: 125743
p: 0.00170

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.26	177	136	1.30	0.00000671	1649
Missense (PolyPhen)		56	43.333	1.2923		561
Synonymous	0.277	45	47.4	0.949	0.00000261	433
Loss of Function	0.643	10	12.4	0.803	5.23e-7	162

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000032	0.000029	rare
Ashkenazi Jewish	0.0030	0.0030	notable
East Asian	0.00016	0.00016	rare
Finnish	0.014	0.014	notable
European (Non-Finnish)	0.00064	0.00064	rare
South Asian	0.00062	0.00062	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May have a role in sperm-egg fusion and maturation.;

Recessive Scores

pRec: 0.0707

Intolerance Scores

LoFtool: 0.976
RVIS EVS: -0.43
RVIS percentile EVS: 25.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.160

Gene Damage Prediction

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