DCAF17

Chr 2AR

DDB1 and CUL4 associated factor 17

Also known as: C20orf37, C2orf37

NCBI Gene: 80067ENSG00000115827UniProt: Q5H9S7

This gene encodes a nuclear transmembrane protein that associates with cullin 4A/damaged DNA binding protein 1 ubiquitin ligase complex. Mutations in this gene are associated with Woodhouse-Sakati syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Woodhouse-Sakati syndromeMIM #241080
AR
508
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DCAF17
🧬
Gene-Disease Validity (ClinGen)
Woodhouse-Sakati syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 127 VUS of 508 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.82LOEUF
pLI 0.000
Z-score 2.30
OE 0.53 (0.35–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.82Z-score
OE missense 0.86 (0.77–0.96)
230 obs / 267.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.53 (0.35–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 15 / 28.2Missense obs/exp: 230 / 267.5Syn Z: 0.56

ClinVar Variant Classifications

508 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic19
VUS127
Likely Benign234
Benign55
Conflicting19
54
Pathogenic
19
Likely Pathogenic
127
VUS
234
Likely Benign
55
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
2
31
0
54
Likely Pathogenic
16
1
2
0
19
VUS
1
67
59
0
127
Likely Benign
0
2
130
102
234
Benign
0
0
52
3
55
Conflicting
—19
Total3872274105508

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

View in ClinVar →

Protein Context — Lollipop Plot

DCAF17 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DCAF17-related Woodhouse-Sakati syndrome

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Woodhouse-Sakati syndrome

MIM #241080

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DCAF17
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding on the phenotypic spectrum of Woodhouse-Sakati syndrome due to founder pathogenic variant in DCAF17: Report of 58 additional patients from Qatar and literature review.
Ali R et al.·Am J Med Genet A
2022Review
Woodhouse-Sakati syndrome: A review.
Messina C·Rev Neurol (Paris)
2025Review
A novel DCAF17 homozygous mutation in a girl with Woodhouse-Sakati syndrome and review of the current literature.
Kurnaz E et al.·J Pediatr Endocrinol Metab
2019Review
Whole exome sequencing and transcript analysis discover a novel pathogenic splice site mutation in DCAF17 gene underlying Woodhouse-Sakati syndrome.
Kumari R et al.·J Neuroendocrinol
2022Case report
Novel inactivating mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model.
Gurbuz F et al.·Clin Genet
2018Functional
Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA).
Wydrych A et al.·Biochim Biophys Acta Mol Basis Dis
2025Cohort
On the complexity of clinical and molecular bases of neurodegeneration with brain iron accumulation.
Tello C et al.·Clin Genet
2018Review
Novel splicing-site mutation in DCAF17 gene causing Woodhouse-Sakati syndrome in a large consanguineous family.
Fozia F et al.·J Clin Lab Anal
2022Case report
Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati syndrome.
Ali RH et al.·Clin Genet
2016
Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review.
Kohil A et al.·Orphanet J Rare Dis
2023Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools