EFHC2

protein-coding

EF-hand domain containing 2, the group of EF-hand domain containing

Gene summary

This gene encodes a protein which contains three DM10 domains and three calcium-binding EF-hand motifs. A related protein is encoded by a gene on chromosome 6. It has been suggested that both proteins are involved in the development of epilepsy (PMID: 15258581, 16112844) and that this gene may be associated with fear recognition in individuals with Turner syndrome. [provided by RefSeq, Aug 2011]

Previous symbols:

MRX74

MANE transcript

NM_025184.4

Inheritance

—

ClinVar variants

U:116B:17

Top phenotype

X-linked intellectual disability

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:44,147,872-44,343,672

External References & Databases

Ensembl (ENSG00000183690)

Transcript & Mutation Effects

hg38 • Region Span ~195.8 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 EFHC2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 86

not providedTotal: 13

X-linked intellectual disabilityTotal: 1

Ornithine carbamoyltransferase deficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025184.4. 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			9 clinvar	4 clinvar		13
missense			98 clinvar	12 clinvar	1 clinvar	111
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	116	16	1	133

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025184.4	RefSeq	NP_079460.2	15	MANE Select
ENST00000420999.2	Ensembl	ENSP00000404232.2	15	MANE Select
ENST00000889038.1	Ensembl	ENSP00000559097.1	15	Standard
ENST00000889038.2	Ensembl	ENSP00000559097.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cellular response to leukemia inhibitory factor

Molecular Function

calcium ion binding
protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000420999
Coding exons: 15
Length: 195791
Individuals with no LoFs: 118292
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 118293
p: 0.00000423

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.622	216	243	0.888	0.0000186	4929
Missense (PolyPhen)		33	59.515	0.55448		1229
Synonymous	0.281	85	88.4	0.962	0.00000670	1325
Loss of Function	4.18	0	20.3	0.00	0.00000141	482

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.0000093	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0954

Intolerance Scores

RVIS EVS: 0.6
RVIS percentile EVS: 82.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.141

Gene Damage Prediction

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