HLTF

protein-coding

helicase like transcription factor, the group of Ring finger proteins

Gene summary

This gene encodes a member of the SWI/SNF family. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein contains a RING finger DNA binding motif. Two transcript variants encoding the same protein have been found for this gene. However, use of an alternative translation start site produces an isoform that is truncated at the N-terminus compared to the full-length protein. [provided by RefSeq, Jul 2008]

Previous symbols:

SNF2L3
SMARCA3

MANE transcript

NM_003071.4

Inheritance

—

ClinVar variants

U:137B:29

Top phenotype

HLTF-related disorder

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr3:149,030,127-149,086,554

External References & Databases

Ensembl (ENSG00000071794)

Transcript & Mutation Effects

hg38 • Region Span ~56.4 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 HLTF variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 121

HLTF-related disorderTotal: 28

not providedTotal: 10

Familial myelodysplastic syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003071.4. 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			3 clinvar	7 clinvar	2 clinvar	12
missense			128 clinvar	15 clinvar	5 clinvar	148
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	137	22	7	166

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003071.4	RefSeq	NP_003062.2	25	MANE Select
ENST00000310053.10	Ensembl	ENSP00000308944.5	25	MANE Select
NM_001318934.2	RefSeq	NP_001305863.1	25	Standard
NM_001318935.2	RefSeq	NP_001305864.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinoblastoma (RB) in Cancer
Post-translational protein modification
Metabolism of proteins
Protein ubiquitination
E3 ubiquitin ligases ubiquitinate target proteins

Biological Process

chromatin organization
regulation of transcription, DNA-templated
protein ubiquitination
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding
RNA binding
helicase activity

Cellular Component

nucleus
nucleoplasm
nucleolus
cytoplasm
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310053
Coding exons: 25
Length: 56428
Individuals with no LoFs: 125405
Homozygous LoFs: 2
Heterozygous LoFs: 340
Defined: 125747
p: 0.00136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.03	441	506	0.872	0.0000251	6613
Missense (PolyPhen)		157	196.46	0.79914		2626
Synonymous	1.82	140	170	0.822	0.00000841	1829
Loss of Function	0.937	47	54.5	0.863	0.00000272	737

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.0013	0.0012	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00061	0.00060	rare
Finnish	0.0069	0.0068	notable
European (Non-Finnish)	0.00073	0.00072	rare
South Asian	0.0011	0.0010	notable
Other	0.0022	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1 and HIV-1 promoters and the SV40 enhancer, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA. {ECO:0000250, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:7876228, ECO:0000269|PubMed:8672239, ECO:0000269|PubMed:9126292}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.0816
RVIS EVS: 0.96
RVIS percentile EVS: 90.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.912

Gene Damage Prediction

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