SUPT16H

protein-coding

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

Gene summary

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]

MANE transcript

NM_007192.4

Inheritance

ClinVar variants

P:8U:194B:21

Top phenotype

Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr14:21,351,476-21,384,019

External References & Databases

Ensembl (ENSG00000092201)

Transcript & Mutation Effects

hg38 • Region Span ~32.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with dysmorphic facies and thin corpus callosumSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859179

Submitter: Labcorp Genetics (formerly Invitae)

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorder with dysmorphic facies and thin corpus callosumLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0859179

Submitter: G2P

neurodevelopmental disorder with dysmorphic facies and thin corpus callosumSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859179

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with dysmorphic facies and thin corpus callosumAD

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 31924697

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUPT16H variants in ClinVar

10 Conditions Cataloged

not providedTotal: 105

Inborn genetic diseasesTotal: 48

Neurodevelopmental disorder with dysmorphic facies and thin corpus callosumTotal: 39

SUPT16H-related disorderTotal: 15

not specifiedTotal: 11

Neurodevelopmental disorderTotal: 2

See casesTotal: 2

Li-Fraumeni syndrome 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007192.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	13 clinvar	4 clinvar	19
missense	4 clinvar	1 clinvar	150 clinvar	4 clinvar		159
nonsense		1 clinvar	11 clinvar			12
start loss						0
frameshift	1 clinvar	1 clinvar	9 clinvar			11
splice donor/acceptor (+/-2bp)			22 clinvar			22
Total	5	3	194	17	4	223

Highest pathogenic variant AF is 6.844121e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007192.4	RefSeq	NP_009123.1	26	MANE Select
ENST00000216297.7	Ensembl	ENSP00000216297.2	26	MANE Select
ENST00000555943.1	Ensembl	ENSP00000450910.1	2	Standard
ENST00000555943.2	Ensembl	ENSP00000450910.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

DNA replication
DNA repair
nucleosome disassembly
transcription by RNA polymerase II
transcription elongation from RNA polymerase II promoter

Molecular Function

RNA binding
protein binding
nucleosome binding
histone binding

Cellular Component

nucleus
nucleoplasm
chromosome
FACT complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216297
Coding exons: 26
Length: 32795
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125747
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	5.10	229	572	0.400	0.0000302	7008
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000098	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.126
RVIS EVS: -0.62
RVIS percentile EVS: 17.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.974

Gene Damage Prediction

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