EFCAB6

protein-coding

EF-hand calcium binding domain 6, the group of EF-hand domain containing

Gene summary

This gene encodes a protein which directly binds the oncogene DJ-1 and androgen receptor to form a ternary complex in cells. This binding protein recruits histone-deacetylase complexes in order to repress transcription activity of androgen receptor. This protein may also play a role in spermatogenesis and fertilization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

MANE transcript

NM_022785.4

Inheritance

—

ClinVar variants

P:2U:263B:23

Top phenotype

Primary ciliary dyskinesia

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr22:43,528,744-43,812,337

External References & Databases

Ensembl (ENSG00000186976)

Transcript & Mutation Effects

hg38 • Region Span ~283.6 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 EFCAB6 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 268

not providedTotal: 7

Primary ciliary dyskinesiaTotal: 3

Prostate cancerTotal: 1

Abnormal sperm morphologyTotal: 1

Reduced sperm motilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022785.4. 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			2 clinvar	2 clinvar		4
missense			257 clinvar	21 clinvar		278
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	1	263	23	0	288

Highest pathogenic variant AF is 0.0060752723

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022785.4	RefSeq	NP_073622.2	30	MANE Select
ENST00000262726.12	Ensembl	ENSP00000262726.7	30	MANE Select
NM_198856.3	RefSeq	NP_942153.1	27	Standard
ENST00000356087.8	Ensembl	ENSP00000348391.4	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Androgen receptor signaling pathway
AndrogenReceptor

Molecular Function

calcium ion binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262726
Coding exons: 30
Length: 283594
Individuals with no LoFs: 123319
Homozygous LoFs: 18
Heterozygous LoFs: 2411
Defined: 125748
p: 0.00971

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.257	843	822	1.03	0.0000454	9936
Missense (PolyPhen)		221	224.81	0.98304		2797
Synonymous	-0.591	340	326	1.04	0.0000209	2755
Loss of Function	0.399	71	74.7	0.950	0.00000375	939

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.0050	0.0050	notable
Ashkenazi Jewish	0.0065	0.0065	notable
East Asian	0.020	0.020	notable
Finnish	0.015	0.015	notable
European (Non-Finnish)	0.0097	0.0096	notable
South Asian	0.011	0.011	notable
Other	0.0088	0.0088	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negatively regulates the androgen receptor by recruiting histone deacetylase complex, and protein DJ-1 antagonizes this inhibition by abrogation of this complex. {ECO:0000269|PubMed:12612053}.;

Recessive Scores

pRec: 0.0853

Intolerance Scores

LoFtool: 0.982
RVIS EVS: 2.23
RVIS percentile EVS: 98.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.333

Gene Damage Prediction

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