SUPT5H

protein-coding

SPT5 homolog, DSIF elongation factor subunit

Gene summary

Enables enzyme binding activity and protein heterodimerization activity. Contributes to RNA polymerase inhibitor activity. Involved in positive regulation of macroautophagy; regulation of DNA-templated transcription; and transcription by RNA polymerase II. Located in nucleoplasm. Part of DSIF complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001111020.3

Inheritance

—

ClinVar variants

P:1U:120B:6

Top phenotype

SUPT5H-related condition

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr19:39,436,156-39,476,670

External References & Databases

Ensembl (ENSG00000196235)

Transcript & Mutation Effects

hg38 • Region Span ~40.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUPT5H variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 12

SUPT5H-related conditionTotal: 2

SUPT5H-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001111020.3. 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			3 clinvar	4 clinvar	1 clinvar	8
missense			98 clinvar	1 clinvar		99
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			17 clinvar			17
Total	0	1	120	5	1	127

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001111020.3	RefSeq	NP_001104490.1	29	MANE Select
ENST00000432763.7	Ensembl	ENSP00000404029.4	29	MANE Select
NM_001130824.2	RefSeq	NP_001124296.1	29	Standard
NM_001130825.2	RefSeq	NP_001124297.1	28	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
supt5h	Danio rerio	Structure: hematopoietic multipotent progenitor cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

supt5h

Danio rerio

Structure: hematopoietic multipotent progenitor cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Initiation of transcription and translation elongation at the HIV-1 LTR
mRNA Processing
Disease
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
Formation of the HIV-1 Early Elongation Complex

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
transcription elongation from RNA polymerase II promoter
7-methylguanosine mRNA capping

Molecular Function

chromatin binding
RNA binding
mRNA binding
protein binding
enzyme binding

Cellular Component

nucleus
nucleoplasm
DSIF complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000599117
Coding exons: 29
Length: 40515
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125748
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.56	353	690	0.511	0.0000434	7138
Missense (PolyPhen)		77	200.45	0.38414		1873
Synonymous	-0.264	274	268	1.02	0.0000174	2087
Loss of Function	7.32	1	64.5	0.0155	0.00000344	698

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV- 1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences. {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.00896
RVIS EVS: -1.42
RVIS percentile EVS: 4.1

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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