DCAF13

Chr 8

DDB1 and CUL4 associated factor 13

Also known as: GM83, HSPC064, Sof1, WDSOF1

NCBI Gene: 25879 ENSG00000164934 UniProt: Q9NV06 OMIM: 616196

The DCAF13 protein functions as a substrate adaptor in the Cul4-RING E3 ubiquitin ligase complex and participates in ribosome biogenesis as part of the small subunit processome that processes 18S rRNA. DCAF13 mutations cause autosomal recessive developmental delay with seizures and intellectual disability, affecting neurological development. The gene plays critical roles in early embryonic development, ribosomal RNA processing, and female meiosis.

OMIM ResearchSummary from RefSeq, UniProt

Enables nuclear estrogen receptor binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including decidualization; epigenetic programming in the zygotic pronuclei; and spindle assembly involved in female meiosis. Located in several cellular components, including centrosome; cytosol; and nuclear lumen. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.85

Clinical Summary— DCAF13

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

74 VUS of 107 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.24

OE 0.59 (0.41–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.69Z-score

OE missense 1.10 (1.01–1.20)

382 obs / 345.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.59 (0.41–0.85)

0≤0.351.4

Missense OE?1.10 (1.01–1.20)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 20 / 34.1Missense obs/exp: 382 / 345.9Syn Z: -1.41

This gene — mechanism propensity

0.6938th %ile

GOF

0.5465th %ile

LOF

0.3841th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

VUS74

Likely Benign3

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	63	11	74
Likely Benign	0	3	3
Benign	0	3	3
Total	63	17	80

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap DCAF13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →