DCAF6

Chr 1

DDB1 and CUL4 associated factor 6

Also known as: 1200006M05Rik, ARCAP, IQWD1, MSTP055, NRIP, PC326

NCBI Gene: 55827 ENSG00000143164 UniProt: Q58WW2 OMIM: 610494

The protein functions as a ligand-dependent coactivator of nuclear receptors including the glucocorticoid receptor and androgen receptor, and may serve as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. Mutations cause autosomal recessive neurodevelopmental disorder with absent language, autistic behaviors, and brain abnormalities. The gene shows high constraint against loss-of-function variants (LOEUF 0.384), indicating that complete loss of protein function is likely deleterious.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

OMIM ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— DCAF6

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

📋

ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 225 VUS of 397 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.086

Z-score 5.28

OE 0.25 (0.16–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.02Z-score

OE missense 0.75 (0.69–0.81)

375 obs / 502.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.25 (0.16–0.38)

0≤0.351.4

Missense OE?0.75 (0.69–0.81)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 14 / 57.0Missense obs/exp: 375 / 502.6Syn Z: -0.96

ClinVar Variant Classifications

397 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic4

VUS225

Likely Benign67

Benign47

Conflicting7

Pathogenic

Likely Pathogenic

225

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	0	0	0	6
Likely Pathogenic	4	0	0	0	4
VUS	1	216	5	3	225
Likely Benign	0	11	31	25	67
Benign	0	2	40	5	47
Conflicting	—				7
Total	11	229	76	33	356

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap DCAF6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →