EFCAB6

Chr 22

EF-hand calcium binding domain 6

Also known as: DJBP, HSCBCIP1, dJ185D5.1

NCBI Gene: 64800 ENSG00000186976 UniProt: Q5THR3 OMIM: 619664

The protein negatively regulates androgen receptor by recruiting histone deacetylase complexes and functions as a microtubule inner protein required for motile cilia beating. Mutations cause autosomal recessive primary ciliary dyskinesia, a disorder affecting respiratory cilia function that typically presents in early childhood with chronic respiratory infections, bronchiectasis, and situs inversus in approximately half of patients. The gene shows moderate constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 0.40

OE 0.95 (0.78–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.26Z-score

OE missense 1.03 (0.97–1.08)

843 obs / 822.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.78–1.16)

0≤0.351.4

Missense OE?1.03 (0.97–1.08)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 71 / 74.7Missense obs/exp: 843 / 822.3Syn Z: -0.59

Background carrier burden — how many people carry a rare variant somewhere in EFCAB6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 25

1,942 rare PASS variants

Rare truncating (LoF)

1 in 220

334 rare PASS variants

Rare synonymous (reference)

1 in 41

742 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EFCAB6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 36	1 in 370
South Asian	~43k	1 in 26	1 in 140
Remaining (unassigned)	~30k	1 in 25	1 in 210
European (Finnish)	~27k	1 in 66	1 in 1,500
Admixed American	~22k	1 in 23	1 in 110
African / African American	~21k	1 in 21	1 in 300
East Asian	~20k	1 in 27	1 in 140
Ashkenazi Jewish	~13k	1 in 71	1 in 900
Middle Eastern	~2,884	1 in 30	1 in 210

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 27 of 30 coding exons well covered in gnomAD exomes; exons 8, 9, 11 marginal. Genomes: all 30.? see exons ↓