HELZ2

protein-coding

helicase with zinc finger 2, the group of UPF1 like RNA helicases

Gene summary

The protein encoded by this gene is a nuclear transcriptional co-activator for peroxisome proliferator activated receptor alpha. The encoded protein contains a zinc finger and is a helicase that appears to be part of the peroxisome proliferator activated receptor alpha interacting complex. This gene is a member of the DNA2/NAM7 helicase gene family. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001037335.2

Inheritance

—

ClinVar variants

U:589B:78

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr20:63,558,086-63,574,239

External References & Databases

Ensembl (ENSG00000130589)

Transcript & Mutation Effects

hg38 • Region Span ~16.2 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 HELZ2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 607

not providedTotal: 28

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001037335.2. 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			10 clinvar	14 clinvar	3 clinvar	27
missense			566 clinvar	58 clinvar	3 clinvar	627
nonsense			10 clinvar			10
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	589	72	6	667

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001037335.2	RefSeq	NP_001032412.2	19	MANE Select
ENST00000467148.2	Ensembl	ENSP00000417401.1	19	MANE Select
NM_033405.3	RefSeq	NP_208384.3	14	Standard
ENST00000427522.6	Ensembl	ENSP00000393257.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
Metabolism of lipids
Metabolism
Transcriptional regulation of white adipocyte differentiation

Biological Process

nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
regulation of lipid metabolic process
positive regulation of transcription by RNA polymerase II
RNA phosphodiester bond hydrolysis

Molecular Function

DNA binding
RNA binding
ATP-dependent RNA helicase activity
ribonuclease activity
protein binding

Cellular Component

nucleoplasm
cytoplasm
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000467148
Coding exons: 19
Length: 16154
Individuals with no LoFs: 125624
Homozygous LoFs: 1
Heterozygous LoFs: 81
Defined: 125706
p: 0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.433	1684	1.73e+3	0.971	0.000130	16690
Missense (PolyPhen)		516	630.41	0.81851		6878
Synonymous	-0.580	817	796	1.03	0.0000632	5696
Loss of Function	5.75	31	89.8	0.345	0.00000430	942

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.00037	0.00030	rare
East Asian	0.00051	0.00049	rare
Finnish	0.00010	0.000092	rare
European (Non-Finnish)	0.00032	0.00030	rare
South Asian	0.00061	0.00056	rare
Other	0.00053	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Helicase that acts as a transcriptional coactivator for a number of nuclear receptors including PPARA, PPARG, THRA, THRB and RXRA. {ECO:0000269|PubMed:16239304, ECO:0000269|PubMed:23525231}.;

Intolerance Scores

RVIS EVS: -0.15
RVIS percentile EVS: 42.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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