CRELD2

protein-coding

cysteine rich with EGF like domains 2

Gene summary

Predicted to enable calcium ion binding activity and protein disulfide isomerase activity. Predicted to be located in Golgi apparatus and endoplasmic reticulum. Predicted to be active in extracellular matrix and obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_024324.5

Inheritance

—

ClinVar variants

U:87B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr22:49,918,167-49,927,540

External References & Databases

Ensembl (ENSG00000184164)

Transcript & Mutation Effects

hg38 • Region Span ~9.4 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 CRELD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024324.5. 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			3 clinvar	3 clinvar	2 clinvar	8
missense			82 clinvar	3 clinvar		85
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	87	6	2	95

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 87 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024324.5	RefSeq	NP_077300.3	10	MANE Select
ENST00000328268.9	Ensembl	ENSP00000332223.4	10	MANE Select
NM_001135101.3	RefSeq	NP_001128573.1	11	Standard
NM_001284317.2	RefSeq	NP_001271246.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

calcium ion binding
protein binding

Cellular Component

extracellular space
endoplasmic reticulum
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000404488
Coding exons: 11
Length: 9374
Individuals with no LoFs: 99501
Homozygous LoFs: 1728
Heterozygous LoFs: 24468
Defined: 125697
p: 0.110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.419	221	239	0.924	0.0000156	2581
Missense (PolyPhen)		83	101.07	0.82122		1120
Synonymous	-0.128	108	106	1.02	0.00000879	741
Loss of Function	1.38	15	22.0	0.683	9.38e-7	265

Population LoF Frequency

Population	CAF	p-value	Status
African	0.31	0.24	notable
Latino/Admixed American	0.085	0.080	notable
Ashkenazi Jewish	0.12	0.11	notable
East Asian	0.058	0.054	notable
Finnish	0.11	0.10	notable
European (Non-Finnish)	0.11	0.10	notable
South Asian	0.16	0.15	notable
Other	0.12	0.11	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May regulate transport of alpha4-beta2 neuronal acetylcholine receptor.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.259
RVIS EVS: 0.8
RVIS percentile EVS: 87.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.486

Gene Damage Prediction

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