SUFU

Chr 10ADARSomatic

SUFU negative regulator of hedgehog signaling

Also known as: BCNS2, JBTS32, PRO1280, SUFUH, SUFUXL

NCBI Gene: 51684ENSG00000107882UniProt: Q9UMX1OMIM: 607035

The protein functions as a negative regulator of the Hedgehog signaling pathway, which controls pattern formation and cellular proliferation during development. Loss-of-function mutations cause autosomal dominant basal cell nevus syndrome 2 and medulloblastoma susceptibility, autosomal recessive Joubert syndrome 32, and somatic mutations contribute to sporadic medulloepitheliomas and meningiomas. The gene is highly intolerant to loss-of-function variation, reflecting its critical role in developmental regulation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/AR/SomaticLOEUF 0.114 OMIM phenotypes
Clinical Summary— SUFU
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Gene-Disease Validity (ClinGen)
medulloblastoma · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 373 VUS of 700 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — SUFU
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 4.80
OE 0.00 (0.00–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.93Z-score
OE missense 0.68 (0.60–0.76)
194 obs / 286.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.11)
0≤0.351.4
Missense OE0.68 (0.60–0.76)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 0 / 26.9Missense obs/exp: 194 / 286.0Syn Z: 0.72
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSUFU-related Joubert syndrome with cranio-facial and skeletal defectsOTHERAR
strongSUFU-related basal cell nevus syndromeOTHERAD
definitiveSUFU-related medulloblastoma, associated with Gorlin syndromeLOFAD
strongSUFU-related Joubert and congenital ocular motor apraxiaOTHERAD
DN
0.3097th %ile
GOF
0.4776th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 87% of P/LP variants are LoF · LOEUF 0.11

Literature Evidence

LOFSUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum.PMID:34675124

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

700 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic14
VUS373
Likely Benign262
Conflicting6
32
Pathogenic
14
Likely Pathogenic
373
VUS
262
Likely Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
26
0
6
0
32
Likely Pathogenic
14
0
0
0
14
VUS
9
330
32
2
373
Likely Benign
0
7
106
149
262
Benign
0
0
0
0
0
Conflicting
—6
Total49337144151687

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

View in ClinVar →

Protein Context — Lollipop Plot

SUFU · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CMA-mediated USP9X degradation promotes SHH medulloblastoma progression by facilitating SUFU ubiquitination.
Gao B et al.·Clin Transl Med
2026Open Access
Multiple hereditary infundibolocystic basal cell carcinoma: report of a sporadic case with a novel pathogenic germline variant in SUFU.
Pascolini G et al.·Dermatol Reports
2026
Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium-Update for Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU).
Smith AL et al.·Neurourol Urodyn
2026Open Access
Why is Bacillus cereus group enriched in sufu? -A study on prevalence, characterization and traceability.
Jin Z et al.·Food Microbiol
2026
Structural and mechanistic insights into the sulfur transfer protein SufU from Staphylococcus aureus.
Sabo E et al.·J Inorg Biochem
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients