SUPT16H

SPT16 homolog, facilitates chromatin remodeling subunit, the group of Armadillo like helical domain containing|M24 metallopeptidase family

Basic information

Region (hg38): 14:21351476-21384019

Links

ENSG00000092201 ∙ NCBI:11198 ∙ OMIM:605012 ∙ HGNC:11465 ∙ Uniprot:Q9Y5B9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with dysmorphic facies and thin corpus callosum (Strong), mode of inheritance: AD
• neurodevelopmental disorder with dysmorphic facies and thin corpus callosum (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	31924697

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUPT16H gene.

• not_provided (68 variants)
• Inborn_genetic_diseases (36 variants)
• Neurodevelopmental_disorder_with_dysmorphic_facies_and_thin_corpus_callosum (24 variants)
• SUPT16H-related_disorder (15 variants)
• not_specified (4 variants)
• Neurodevelopmental_disorder (2 variants)
• See_cases (2 variants)
• Li-Fraumeni_syndrome_1 (1 variants)
• Conotruncal_defect (1 variants)
• Dextrocardia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUPT16H gene is commonly pathogenic or not. These statistics are base on transcript: NM_000007192.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	5	14
missense	4	1	104	3		112
nonsense		1	7			8
start loss						0
frameshift			5			5
splice donor/acceptor (+/-2bp)			2			2
Total	4	2	118	12	5

Highest pathogenic variant AF is 6.844121e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUPT16H	protein_coding	protein_coding	ENST00000216297	26	32795

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	8.16e-9	125736	0	11	125747	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.10	229	572	0.400	0.0000302	7008
Missense in Polyphen		26	178.6	0.14557		2200
Synonymous	0.294	194	199	0.974	0.0000107	1852
Loss of Function	7.10	3	64.6	0.0465	0.00000389	740

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000534	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9836642}.
• Pathway: Disease;Gene expression (Transcription);Formation of HIV-1 elongation complex containing HIV-1 Tat;Tat-mediated elongation of the HIV-1 transcript;HIV Transcription Elongation;HIV elongation arrest and recovery;Formation of HIV elongation complex in the absence of HIV Tat;Pausing and recovery of HIV elongation;Generic Transcription Pathway;Tat-mediated HIV elongation arrest and recovery;Pausing and recovery of Tat-mediated HIV elongation;Transcription of the HIV genome;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;RNA Polymerase II Pre-transcription Events;Formation of RNA Pol II elongation complex ;RNA Polymerase II Transcription;Infectious disease;RNA Polymerase II Transcription Elongation;TP53 Regulates Transcription of DNA Repair Genes;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.126
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.31

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.840
• ghis: 0.676

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Supt16

Gene ontology

• Biological process: DNA replication;DNA repair;nucleosome disassembly;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;positive regulation of DNA-templated transcription, elongation;positive regulation of transcription elongation from RNA polymerase II promoter;DNA replication-independent nucleosome organization;regulation of signal transduction by p53 class mediator
• Cellular component: nucleus;nucleoplasm;chromosome;FACT complex
• Molecular function: RNA binding;protein binding;nucleosome binding;histone binding