SUPT16H

Chr 14

SPT16 homolog, facilitates chromatin remodeling subunit

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

NCBI Gene: 11198 ENSG00000092201 UniProt: Q9Y5B9

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.

ResearchSummary from RefSeq, OMIM, UniProt

Transcription of protein-coding genes can be reconstituted on naked DNA with only the general transcription factors and RNA polymerase II. However, this minimal system cannot transcribe DNA packaged into chromatin, indicating that accessory factors may facilitate access to DNA. One such factor, FACT (facilitates chromatin transcription), interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT is composed of an 80 kDa subunit and a 140 kDa subunit; this gene encodes the 140 kDa subunit. [provided by RefSeq, Feb 2009]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.12

Clinical Summary— SUPT16H

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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

11 unique Pathogenic / Likely Pathogenic· 147 VUS of 222 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 7.10

OE 0.05 (0.02–0.12)

Highly constrained

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

Missense Constraint?

5.10Z-score

OE missense 0.40 (0.36–0.45)

229 obs / 572.4 exp

Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.12)

0≤0.351.4

Missense OE?0.40 (0.36–0.45)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 3 / 64.6Missense obs/exp: 229 / 572.4Syn Z: 0.29

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedSUPT16H-related neurodevelopmental disorderOTHERAD

This gene — mechanism propensity

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 · 27% of P/LP variants are LoF · 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

222 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic4

VUS147

Likely Benign17

Benign8

Pathogenic

Likely Pathogenic

147

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	4	2	0	7
Likely Pathogenic	2	2	0	0	4
VUS	17	124	5	1	147
Likely Benign	0	4	3	10	17
Benign	0	1	2	5	8
Total	20	135	12	16	183

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap SUPT16H — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →