CGREF1

protein-coding

cell growth regulator with EF-hand domain 1, the group of EF-hand domain containing

Gene summary

Predicted to enable calcium ion binding activity. Predicted to be involved in negative regulation of cell population proliferation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_006569.6

Inheritance

—

ClinVar variants

U:45B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.27

Max pathogenic AF

—

Genomic locus

chr2:27,098,889-27,119,128

External References & Databases

Ensembl (ENSG00000138028)

Transcript & Mutation Effects

hg38 • Region Span ~20.2 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 CGREF1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 46

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006569.6. 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			2 clinvar	1 clinvar		3
missense			42 clinvar	3 clinvar		45
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	45	4	0	49

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006569.6	RefSeq	NP_006560.3	5	MANE Select
ENST00000402394.6	Ensembl	ENSP00000385452.1	5	MANE Select
NM_001166239.2	RefSeq	NP_001159711.1	5	Standard
NM_001166240.2	RefSeq	NP_001159712.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle arrest
cell adhesion
negative regulation of cell population proliferation

Molecular Function

calcium ion binding

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402394
Coding exons: 5
Length: 20239
Individuals with no LoFs: 125536
Homozygous LoFs: 0
Heterozygous LoFs: 212
Defined: 125748
p: 0.000843

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	131	169	0.775	0.00000820	2030
Missense (PolyPhen)		41	43.912	0.93369		564
Synonymous	-0.330	76	72.4	1.05	0.00000380	680
Loss of Function	-0.711	10	7.85	1.27	3.33e-7	89

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00031	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0035	0.0035	notable
Finnish	0.0011	0.0011	notable
European (Non-Finnish)	0.00058	0.00058	rare
South Asian	0.0013	0.0013	notable
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates cell-cell adhesion in a calcium-dependent manner (By similarity). Able to inhibit growth in several cell lines. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.700
RVIS EVS: 0.44
RVIS percentile EVS: 77.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00179

Gene Damage Prediction

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