SUPT16H

Chr 14AD

SPT16 homolog, facilitates chromatin remodeling subunit

Also known as: CDC68, FACTP140, NEDDFAC, SPT16, SPT16/CDC68

SUPT16H encodes the 140 kDa subunit of the FACT chromatin remodeling complex, which acts as a histone chaperone to facilitate nucleosome disassembly and reassembly during transcription elongation, DNA replication, and repair. Mutations cause autosomal dominant neurodevelopmental disorder with dysmorphic facies and thin corpus callosum. This gene is extremely intolerant to loss-of-function variants (pLI = 1.0, LOEUF = 0.12), indicating high constraint against protein-truncating mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical SummarySUPT16H
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 7.10
OE 0.05 (0.020.12)
Highly constrained

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

Missense Constraint
5.10Z-score
OE missense 0.40 (0.360.45)
229 obs / 572.4 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.05 (0.020.12)
00.351.4
Missense OE0.40 (0.360.45)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 3 / 64.6Missense obs/exp: 229 / 572.4Syn Z: 0.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedSUPT16H-related neurodevelopmental disorderOTHERAD
DN
0.3196th %ile
GOF
0.3491th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.12

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SUPT16H · 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

No active trials found for this gene.

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Clinical Literature
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